Genetics and Metabolic Flashcards
(342 cards)
1
Q
How many chromosomes are there in a normal human somatic cell?
A
46 chromosomes (23 pairs).
2
Q
Where are chromosomes located inside the cell?
A
Inside the nucleus.
3
Q
What is a chromosome made of?
A
DNA wrapped around histone proteins, forming an X shape during cell division.
4
Q
What are chromosomal abnormalities?
A
Changes in chromosome number or structure.
5
Q
What is aneuploidy?
A
Abnormal number of chromosomes
## footnote
either extra or missing.
6
Q
Give examples of aneuploidy.
A
• Trisomy 21 (Down syndrome) → extra chromosome 21.
• Monosomy X (Turner syndrome) → missing one X chromosome.
## footnote
Turner ➡️ 45 chromosome
Down ➡️ 47 chromosome
7
Q
What are structural chromosomal abnormalities?
A
Alterations in chromosome structure
## footnote
(e.g., deletions, duplications, inversions, translocations).
8
Q
What is genomic imprinting?
A
Gene expression depends on whether the gene is inherited from the mother or father.
9
Q
Give an example of a disorder due to genomic imprinting.
A
• Prader-Willi syndrome (paternal deletion).
• Angelman syndrome (maternal deletion).
🪄🪄
P rader ➡️ P aternal
Angel M an ➡️ M aternal
10
Q
What is mitochondrial inheritance?
A
Transmission of genes through mitochondrial DNA, inherited only from the mother.
11
Q
What is expansion of trinucleotide repeats?
A
DNA mutations where a sequence of three nucleotides is abnormally repeated, causing disease.
12
Q
Give examples of trinucleotide repeat disorders.
A
• Huntington’s disease.
• Fragile X syndrome.
• Myotonic dystrophy.
13
Q
What is trisomy?
A
Gain of one chromosome (47 total chromosomes).
14
Q
Which trisomy causes Down syndrome?
A
47, +21.
15
Q
Which trisomy causes Edwards syndrome?
A
47, +18.
16
Q
Which trisomy causes Patau syndrome?
A
47, +13.
17
Q
What is the karyotype of Klinefelter syndrome?
A
47, XXY
## footnote
(male with extra X chromosome).
18
Q
What are types of structural chromosomal abnormalities?
A
- Deletion.
- Duplication.
- Translocation.
19
Q
What is a deletion?
A
Loss of a chromosome segment.
20
Q
What is a duplication?
A
Repetition of a chromosome segment.
21
Q
What is a translocation?
A
Transfer of a segment from one chromosome to another.
## footnote
Translocations can be balanced (no symptoms) or unbalanced (cause disease).
22
Q
What is a reciprocal translocation?
A
Exchange of segments between two non-homologous chromosomes.
23
Q
What is a Robertsonian translocation?
A
Fusion of two acrocentric chromosomes at their centromeres with loss of short arms.
## footnote
• Common Robertsonian combinations: (21;14), (21;21), (13;14).
• Robertsonian translocations involving chromosomes 21 and 14 can lead to familial Down syndrome.
24
Q
What is a balanced translocation?
A
Exchange of genetic material without loss or gain
## footnote
(usually no phenotype).
25
Which chromosomes are involved in Robertsonian translocations?
Acrocentric chromosomes: 13, 14, 15, 21, 22.
26
What is autosomal dominant inheritance?
Presence of one abnormal gene on one of the autosomes (chromosomes 1–22) causes disease.
27
Are both sexes affected and able to transmit in autosomal dominant diseases?
Yes, both sexes are equally affected and can transmit the disorder.
28
Are generations skipped in autosomal dominant inheritance?
No, unless there is incomplete penetrance.
29
What is the probability of an affected individual transmitting the disorder to offspring?
50%.
30
Does every affected child have an affected parent?
Yes.
## footnote
* except in cases of new (spontaneous) mutations.
* Spontaneous mutations are a common cause of achondroplasia and some cases of neurofibromatosis type 1.
31
Which of the following is an autosomal dominant disorder?
A) Cystic fibrosis
B) Achondroplasia
C) Duchenne muscular dystrophy
D) Phenylketonuria
B) Achondroplasia
## footnote
* Cystic fibrosis → Autosomal recessive
* Duchenne muscular dystrophy → X-linked recessive
* Phenylketonuria (PKU) → Autosomal recessive
32
What is autosomal recessive inheritance?
Disease occurs when both copies (alleles) of a gene on an autosome (chromosomes 1–22) are mutated.
33
Are both sexes equally affected in autosomal recessive disorders?
Yes
34
What is the recurrence risk for parents with a previously affected child?
25%.
35
Does consanguinity increase the risk of autosomal recessive disorders?
True.
36
Which of the following is an autosomal recessive disorder?
A) Marfan syndrome
B) Familial Mediterranean fever
C) Huntington disease
D) Neurofibromatosis type 1
B) Familial Mediterranean fever
## footnote
• Marfan syndrome → Autosomal dominant.
• Huntington disease → Autosomal dominant.
• Neurofibromatosis type 1 → Autosomal dominant.
37
How is X-linked recessive inheritance transmitted?
Through a mutated gene on the X chromosome.
38
In X-linked recessive inheritance, who can transmit the disease to sons?
Only carrier females.
39
Are female carriers usually symptomatic in X-linked recessive disorders?
False
## footnote
They are generally asymptomatic.
40
What is the risk for a carrier female to have an affected son?
25%.
41
What is the risk for a carrier female to have a carrier daughter?
25%.
42
What is the chance for a carrier female to have a completely unaffected child (non-carrier, non-affected)?
50%.
43
In X-linked recessive inheritance, what happens when a male is affected?
• 100% of his daughters will be carriers.
• All his sons will be normal (since sons inherit the Y chromosome from the father).
44
Which of the following diseases is X-linked recessive?
A) Cystic fibrosis
B) G6PD deficiency
C) Achondroplasia
D) Marfan syndrome
B) G6PD deficiency
## footnote
• Cystic fibrosis → Autosomal recessive.
• Achondroplasia → Autosomal dominant.
• Marfan syndrome → Autosomal dominant.
45
Examples of X-linked recessive disorders:
• Hemophilia A and B
• Duchenne muscular dystrophy
• G6PD deficiency
46
In Prader-Willi syndrome, which parent transmits the affected gene?
The father.
## footnote
In Prader-Willi syndrome, the father’s gene is missing or inactive, and the mother’s gene is naturally silenced by imprinting.
47
What chromosomal region is involved in Prader-Willi syndrome?
15q11–13 (band 11–13 of the long arm of chromosome 15).
48
In Prader-Willi syndrome, is the maternal allele active or silent?
Silent (inactive).
49
Which of the following is NOT a feature of Prader-Willi syndrome?
A) Hyperphagia
B) Obesity
C) Tall stature
D) Hypogonadism
C) Tall stature
50
What causes Angelman syndrome?
Loss of maternal gene expression at 15q11–13; paternal allele is inactive (imprinting).
51
What are key clinical features of Angelman syndrome?
• Frequent laughter (“happy puppet” appearance)
• Intellectual disability
• Speech delay
• Microcephaly
• Epilepsy
• Ataxia
52
Where is (mtDNA) located?
In the mitochondria
## footnote
mtDNA is the only genetic material outside the nucleus.
53
How are mitochondrial disorders inherited?
Maternally
## footnote
An affected mother passes abnormal mtDNA to all her offspring.
54
Can fathers transmit mitochondrial diseases?
Rarely
## footnote
Sperm contain very few mitochondria.
55
Which of the following disorders is inherited through mitochondrial DNA?
A) Duchenne muscular dystrophy
B) MELAS syndrome
C) Achondroplasia
D) Thalassemia
B) MELAS syndrome
## footnote
1. MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes).
2. Other options:
• Duchenne muscular dystrophy → X-linked recessive.
• Achondroplasia → Autosomal dominant.
• Thalassemia → Autosomal recessive.
56
Name two examples of mitochondrial disorders.
• MELAS syndrome
• Kearns-Sayre syndrome
57
All offspring (sons and daughters) of a mother with a mitochondrial disorder may inherit the disease. (True/False)
True.
58
What does multifactorial inheritance mean?
A condition caused by a combination of genetic and environmental factors.
59
In multifactorial inheritance, is one gender often more affected than the other?
Yes.
60
Give an example of a disorder showing multifactorial inheritance.
Developmental Dysplasia of the Hip (DDH)
## footnote
It is more common in females.
61
Multifactorial diseases are caused only by genetic mutations. (True/False)
False.
## footnote
They involve both genetic and environmental factors.
62
Which of the following is an indication for genetic testing?
A) Single miscarriage
B) Developmental abnormalities
C) Normal family history
D) No congenital anomalies
B) Developmental abnormalities
63
Consanguinity between parents increases the risk for which of the following?
A) Acquired infections
B) Genetic disorders
C) Environmental poisoning
D) Nutritional deficiencies
B) Genetic disorders
64
When should genetic testing be considered based on congenital anomalies?
• 1 major anomaly, OR
• ≥ 3 minor anomalies.
65
Which of the following is considered a major congenital anomaly?
A) Ear tags
B) Syndactyly of 2-3 toes
C) Omphalocele
D) Epicanthal folds
C) Omphalocele
## footnote
Ear tags, syndactyly, and epicanthal folds → Minor anomalies.
66
Which anomaly suggests the need for genetic testing even if found alone?
A) 2-3 toes syndactyly
B) Ear tags
C) Cleft lip/palate
D) Hypertelorism
C) Cleft lip/palate
## footnote
One major or 3 or more minor.
• Major anomalies → Brain defects, congenital heart defects, cleft lip/palate, omphalocele, limb absence.
• Minor anomalies → Ear tags, syndactyly of 2-3 toes, epicanthal folds, hypertelorism.
67
Which of the following samples can be used for chromosome analysis?
A) Saliva
B) Packed red blood cells
C) Peripheral blood lymphocytes
D) Urine
C) Peripheral blood lymphocytes
68
What are common sources used for chromosome analysis?
• Peripheral blood lymphocytes
• Amniotic fluid <8w gestation
• Cultured skin fibroblasts
• Bone marrow cells
69
Which statement is TRUE regarding packed red blood cell transfusion and genetic testing?
A) It alters the genetic results.
B) It does not affect genetic testing.
C) It delays genetic testing.
D) It causes genetic mutations.
B) It does not affect genetic testing.
## Footnote:
• Packed red blood cells are enucleated (no nucleus → no DNA), so transfusion does not interfere with chromosome analysis.
70
What does a karyotype test evaluate?
• Size of chromosomes
• Shape of chromosomes
• Number of chromosomes
71
Which of the following can be detected by a standard G-banded karyotype?
A) Subtle point mutations
B) Trisomy 21
C) Small single nucleotide variants
D) Microdeletions less than 5 Mb
B) Trisomy 21
72
What genetic abnormalities can be detected by a karyotype?
• Trisomies (e.g., Down syndrome)
• Sex chromosomal anomalies (e.g., Turner, Klinefelter)
• Visible deletions, duplications, and translocations
73
A G-banded karyotype can completely rule out all subtle chromosomal abnormalities. (True/False)
False
## footnote
• Limitation: Karyotype has a resolution limit → cannot detect small or very subtle chromosomal abnormalities (like microdeletions or single-gene mutations).
74
What is the main use of DNA microarray in genetic testing?
• Detecting microdeletions and microduplications
• Identifying specific chromosomal breakpoints
75
DNA microarray is particularly useful in evaluating which of the following conditions?
A) Single gene disorders
B) Multiple congenital anomalies
C) Metabolic disorders
D) Infectious diseases
B) Multiple congenital anomalies
76
Name 3 clinical indications for ordering a DNA microarray.
• Autism spectrum disorder
• Developmental delay
• Multiple congenital anomalies
77
DNA microarray is better than karyotype for detecting very small chromosomal changes. (True/False)
True.
## footnote
• Microarray = High-resolution tool for detecting small copy number variations (CNVs) that are invisible to conventional karyotyping.
78
What does FISH analysis detect?
• A specific DNA sequence on a chromosome using a fluorescent-labeled DNA probe.
79
How are FISH results interpreted?
• 2 signals → Normal
• 1 signal → Microdeletion
80
FISH analysis is particularly useful in diagnosing which of the following syndromes?
A) Down syndrome
B) DiGeorge syndrome (22q11.2 deletion)
C) Turner syndrome
D) Fragile X syndrome
B) DiGeorge syndrome
81
Give examples of conditions detectable by FISH analysis.
• 22q11.2 microdeletion (DiGeorge syndrome)
• William’s syndrome
82
In FISH, a finding of one fluorescent signal indicates a duplication. (True/False)
False — it indicates a **microdeletion** .
## footnote
• FISH is highly targeted: only detects what the probe is designed for → good for known suspected deletions or duplications, not for general screening.
83
What is the most common chromosomal disorder in humans?
Down syndrome.
84
What is the most common genetic cause of intellectual disability?
Down syndrome.
85
Down syndrome always presents with the same clinical features in all patients. (True/False)
False.
## footnote
There is a wide range of phenotypic variation.
86
Name two general characteristics of Down syndrome.
• Multiple systemic complications.
• Variable phenotypic expression (different degrees of severity between individuals).
## footnote
•Key point: 🔐
Although Down syndrome is consistently caused by trisomy 21 (in most cases), the severity and type of complications can vary widely between individuals.
87
Which mechanism causes Down syndrome in 95% of cases?
A) Robertsonian translocation
B) Nondisjunction
C) Mosaicism
D) Point mutation
B) Nondisjunction
## footnote
leading to trisomy 21 (47, +21)
88
What percentage of Down syndrome cases are caused by Robertsonian translocation?
4%
89
What percentage of Down syndrome cases are due to mosaicism?
1%
## footnote
• Mosaicism = Some cells have trisomy 21 while others have normal chromosomes → usually milder phenotype.
90
What is the recurrence risk for a couple who had a child with Down syndrome caused by nondisjunction?
1–4%, plus 1% extra added to maternal age-related risk.
91
What should be done if a child with Down syndrome is confirmed to have Robertsonian translocation?
Test the parents to determine carrier status and assess recurrence risk.
92
If the mother carries a 14q:21q Robertsonian translocation, what is the recurrence risk?
10-15%.
93
If the mother carries a 21q:21q translocation, what is the recurrence risk?
Nearly 100%.
94
What are general clinical features seen in Down syndrome?
• Hypotonia
• Intellectual disability (ID)
• Small, brachycephalic head
• Small ears and mouth
• Brachydactyly (short fingers)
• Hypoplasia of the middle phalanx of the fifth finger → Clinodactyly
• Up-slanted palpebral fissures
• Single transverse palmar crease
95
What are eye-related features seen in Down syndrome?
• Speckled iris (Brushfield spots)
• Cataracts (15% risk)
• Severe refractive errors (50% risk)
• Strabismus
96
What cardiac defect is most commonly associated with Down syndrome?
Endocardial cushion defect (atrioventricular septal defect).
97
What GI conditions are associated with Down syndrome?
• Duodenal atresia
• Hirschsprung disease
• TEF/GERD
## footnote
* Deodenal atresia ➡️ (“double bubble” sign)
* Hurshsprug disease ➡️ (failure to pass meconium, constipation)
* TEF/GERD➡️ (choking with feeds, recurrent pneumonia)
• GI symptoms like bilious vomiting require urgent evaluation for duodenal atresia.
98
What should be done for every newborn with Down syndrome even if no heart murmur is detected?
Echocardiogram.
99
What autoimmune GI disease is screened for at 2 years of age or earlier in Down syndrome?
Celiac disease.
## footnote
(tissue transglutaminase IgA).
100
What feeding problems can be seen in infants with Down syndrome?
• Choking with feeds
• Recurrent pneumonia
• Failure to thrive
101
What hearing tests are recommended in Down syndrome?
• Brainstem auditory evoked response (BAER)
• Otoacoustic emission (OAE)
→ At birth or by 3 months.
102
What hearing tests are recommended in Down syndrome?
• Brainstem auditory evoked response (BAER)
• Otoacoustic emission (OAE
## footnote
OAE → At birth or by 3 months.
103
Why are children with Down syndrome at higher risk for obstructive sleep apnea?
Due to a narrow airway.
104
When should screening for obstructive sleep apnea begin in Down syndrome patients?
At 1 year of age, and repeated at each visit or when symptomatic.
105
What type of leukemia is more common in children with Down syndrome?
Acute megakaryocytic leukemia (AML).
106
Children with Down syndrome are at higher risk for transient myeloproliferative disorders. (True/False)
True.
107
What hematologic findings should trigger further workup in Down syndrome newborns?
• Easy bruising
• Petechiae
• Lethargy
• Change in feeding patterns
108
What is the prevalence of congenital hypothyroidism in Down syndrome?
~1%.
109
What is the prevalence of acquired hypothyroidism later in Down syndrome?
3–5%.
110
When should thyroid function tests (TSH and Free T4) be done in Down syndrome?
• At 3 months
• At 6 months
• At 12 months
• Then annually
111
What screening is recommended for atlantoaxial instability in Down syndrome?
• Physical exam each visit
• Cervical spine radiographs at 3–5 years old or before contact sports.
112
Symptoms of atlantoaxial instability include…?
• Neck pain
• Limited neck mobility
• Difficulty walking
• Loss of motor skills
• Weakness
• Abnormal reflexes
113
Radiographic screening for atlantoaxial instability is only needed if neurological symptoms appear. (True/False)
False
## footnote
Should also be done proactively in certain cases (e.g., before sports).
114
Should children with Down syndrome receive routine immunizations?
Yes — same as the general population schedule.
115
What is the chromosomal abnormality in Edwards syndrome?
Trisomy 18 (an extra chromosome 18).
116
What is the intellectual impact of Trisomy 18?
Severe intellectual disability (100% of cases).
117
What are the main craniofacial features seen in Trisomy 18?
• Microcephaly (small head)
• Microphthalmia (small eyes)
• Low-set ears
• Elongated skull with prominent occiput
118
What are the characteristic limb findings in Trisomy 18?
• Rocker bottom feet (prominent calcaneus)
• Clubfoot
• Clenched fists with overlapping fingers
119
What cardiac defect is commonly associated with Trisomy 18?
Ventricular Septal Defect (VSD).
120
How does Trisomy 18 affect growth and survival?
• Failure to thrive (FTT)
• Most affected infants die within the first year of life.
121
Which of the following findings is most characteristic of Trisomy 18 (Edwards syndrome)?
A. Single palmar crease
B. Rocker bottom feet
C. Brushfield spots
D. Cleft lip and palate
B. Rocker bottom feet
## footnote
• Single palmar crease → seen in Down syndrome.
• Brushfield spots → seen in Down syndrome.
• Cleft lip/palate → more common in Trisomy 13 (Patau syndrome).
122
What is the chromosomal abnormality in Patau syndrome?
Trisomy 13 (an extra chromosome 13).
123
What are the major craniofacial features of Trisomy 13?
• Microcephaly (small head)
• Microphthalmia (small eyes)
• Scalp defects (cutis aplasia)
• Cleft lip and/or cleft palate
124
What major brain abnormality is seen in Trisomy 13?
Holoprosencephaly (failure of forebrain to divide properly).
125
What limb anomaly is typical in Trisomy 13?
Postaxial polydactyly (extra finger on the ulnar side).
126
What are the common cardiac defects associated with Trisomy 13?
• Patent ductus arteriosus (PDA)
• Ventricular septal defect (VSD)
127
What are some abdominal wall defects associated with Trisomy 13?
• Omphalocele
• Hernias (umbilical or inguinal)
128
How does Trisomy 13 affect survival?
• It is the least common but most severe of the trisomies.
• Most affected infants die within the first weeks to months of life.
129
How does maternal age affect the risk of Trisomy 13?
Increased maternal age raises the risk, but overall recurrence risk remains <1%.
130
What genital anomalies may be seen in Trisomy 13?
• Abnormal genitalia (e.g., cryptorchidism, ambiguous genitalia).
131
Which of the following findings is most specific for Trisomy 13 (Patau syndrome)?
A. Brushfield spots
B. Holoprosencephaly
C. Rocker bottom feet
D. Single palmar crease
B. Holoprosencephaly
## footnote
• Brushfield spots → Down syndrome.
• Rocker bottom feet → seen mainly in Trisomy 18 (Edwards syndrome).
• Single palmar crease → Down syndrome.
• Holoprosencephaly → classic brain defect in Patau syndrome.
132
What is the chromosomal abnormality in Klinefelter syndrome?
Presence of an extra X chromosome in males (47, XXY).
133
What is the pathognomonic feature of Klinefelter syndrome?
Hypogonadism (small testes, reduced testosterone).
134
What are the physical features commonly seen in Klinefelter syndrome?
• Tall stature
• Gynecomastia (breast development in males)
• Small penis
135
What are the academic and psychological impacts of Klinefelter syndrome?
• Language impairment
• Academic difficulties
• Poor self-esteem
• Behavioral problems
136
What are additional systemic features associated with Klinefelter syndrome?
• Fatigue and weakness
• Osteoporosis (due to low testosterone)
• Infertility (azoospermia)
137
Which of the following is considered pathognomonic for Klinefelter syndrome?
A. Tall stature
B. Infertility
C. Hypogonadism
D. Gynecomastia
C. Hypogonadism
## Footnote:
• Tall stature and gynecomastia are common but not specific.
• Hypogonadism (testicular failure) is pathognomonic and defines the syndrome.
138
What types of cancers are patients with Klinefelter syndrome at increased risk for?
• Testicular germ cell tumors
• Breast cancer (higher risk compared to general male population)
## footnote
• Breast cancer risk: Patients should be counseled about self-exam and possibly screening based on clinical findings.
139
What is the recommended treatment for Klinefelter syndrome starting at puberty?
Testosterone replacement therapy, starting around age 12 years.
## footnote
• Testosterone therapy: Improves secondary sexual characteristics, muscle mass, bone density, and can improve mood and self-esteem.
140
What laboratory findings are typical in Klinefelter syndrome?
• High LH and FSH (due to primary gonadal failure)
• High estradiol
• Low serum testosterone
141
What is the karyotype finding in most patients with Klinefelter syndrome?
47,XXY in 80-90% of cases.
142
What karyotype variations can also be seen in Klinefelter syndrome?
• Mosaicism (46,XY/47,XXY)
• Higher grade aneuploidies like 48,XXXY or 49,XXXXY (more severe phenotype).
## footnote
The number of X chromosomes correlated with final intelligence, each increase in x chromosome is more delay in intelligence.
143
Which laboratory finding is most characteristic of Klinefelter syndrome?
A. High serum testosterone
B. High LH and FSH
C. Low estradiol
D. Normal LH and FSH
B. High LH and FSH
## Footnote:
• Low testosterone leads to loss of feedback inhibition, causing elevated LH and FSH.
• Estradiol may also be elevated, contributing to gynecomastia.
144
What is the most common inherited cause of intellectual disability?
Fragile X syndrome.
145
What is the inheritance pattern of Fragile X syndrome?
X-linked inheritance
146
What are the key neurodevelopmental and behavioral features in Fragile X syndrome?
• Intellectual disability
• Hyperkinetic behavior (hyperactivity)
• Autistic-like features
• Aggressive behavior
• Cluttered speech and stuttering
147
148
What are the typical physical signs that appear around puberty in Fragile X syndrome?
• Macrocephaly (large head)
• Large ears
• Macro-orchidism (enlarged testes; may be subtle early)
149
What is the genetic defect in Fragile X syndrome?
• Expansion of CGG triplet repeats (>200 repeats) on the FMR1 gene.
• Dramatic expansion seen in affected males (400–1000 repeats).
150
What is the diagnostic test for Fragile X syndrome?
• Fragile X DNA analysis (molecular genetic testing to detect CGG expansion).
151
A 14-year-old boy presents with developmental delay and learning difficulties. Examination reveals elongated face, micropenis, and large testicles. Which of the following is the most likely diagnosis?
A. Down syndrome
B. Klinefelter syndrome
C. Fragile X syndrome
D. Williams syndrome
C. Fragile X syndrome
## footnote
• Fragile X is characterized by elongated face, macro-orchidism, and intellectual disability, especially in pubertal males.
• Klinefelter syndrome typically presents with small testes and gynecomastia.
152
What is the classic karyotype in Turner syndrome?
45,X (Monosomy X — missing one X chromosome).
153
What are other possible karyotypes in Turner syndrome?
• 45,X/46,XX (mosaicism)
• 45,X/46,XY (mosaicism)
• 46,XX with structural abnormalities of the X chromosome (e.g., isochromosome).
154
What are the main physical features of Turner syndrome?
• **Short stature**
• **Webbed neck**
• Low posterior hairline
• **Shield chest with widely spaced nipples**
• High-arched palate
• Dental crowding
• **Lymphedema** (hands and feet)
• Hypoplastic or hyperconvex nails
• Short 4th and 5th metacarpals/metatarsals
• Excessive number of nevi
155
What are the key organ system anomalies in Turner syndrome?
• Gonadal dysgenesis → ovarian failure → primary amenorrhea
• **Hearing loss** 🦻
• **Horseshoe kidney**
• Cardiac anomalies 🫀: bicuspid aortic valve, **coarctation of the aorta** , risk of aortic dissection
• Endocrine issues: hypothyroidism, glucose intolerance, hyperlipidemia
• Orthopedic issues: scoliosis, Madelung deformity
## footnote
* Primary amenorrhea and lack of secondary sexual characteristics are critical red flags.
* Cardiac evaluation is crucial due to risk of aortic dissection.
156
What is the management plan for Turner syndrome?
• **Growth hormone therapy** : start as early as 2 years old if height < 5th percentile.
• **Estrogen replacement therapy** :
* Start around 12 years if height is acceptable.
* Can be delayed up to 15 years to maximize height.
• Symptomatic treatment based on specific organ involvement.
157
A 10-year-old girl presents with short stature, a webbed neck, widely spaced nipples, and primary amenorrhea. Physical exam reveals lymphedema of hands and feet and a history of congenital heart defects. Which of the following is the most likely diagnosis?
A. Turner syndrome
B. Klinefelter syndrome
C. Fragile X syndrome
D. Noonan syndrome
A. Turner syndrome
## footnote
Short stature + Webbed neck + Gonadal dysgenesis + Cardiac anomalies → strongly suggest Turner syndrome.
158
A 5-year-old boy presents with short stature, curly hair, webbed neck, small chin, and cryptorchidism. Cardiac exam reveals a systolic murmur consistent with pulmonary stenosis. His karyotype is normal. What is the most likely diagnosis?
A. Turner syndrome
B. Klinefelter syndrome
C. Noonan syndrome
D. Fragile X syndrome
C. Noonan syndrome
## footnote
• If the child has Turner-like features but normal karyotype and is male, think Noonan.
• Pulmonary valve stenosis is very characteristic.
• Cryptorchidism (undescended testes) and bleeding tendency are also supportive clues.
159
What is the genetic cause of Noonan syndrome?
• Mostly due to PTPN11 gene mutations (~50% of cases).
• Inheritance: Autosomal Dominant (can be sporadic too).
160
How does Noonan syndrome differ from Turner syndrome?
• Affects both males and females equally (unlike Turner).
• Features are Turner-like but karyotype is normal (not 45,X).
161
What are the key physical features in Noonan syndrome?
• Curly/wooly hair
• Wide forehead
• Small chin
• **Short stature**
• Cubitus valgus
• Cryptorchidism
• Small penis
• **Short webbed neck**
162
What are important systemic findings in Noonan syndrome?
• **Intellectual disability (~25%)**
• Pulmonary valve stenosis (common cardiac defect)
• Bleeding disorders (coagulation defects)
• Slight increased risk of malignancy
163
What is the pattern of inheritance of Noonan syndrome?
A) Autosomal Recessive
B) Not inherited
C) Autosomal Dominant
D) X-linked
C) Autosomal Dominant
164
True or False:
Turner syndrome affects both males and females.
False — Turner syndrome affects only females.
165
When do symptoms of metabolic disorders typically appear?
Normal at birth → symptoms develop hours to years later, depending on the disorder type.
166
Children with Williams Syndrome often have a “cocktail party” personality characterized by friendliness.
True
167
What genetic abnormality is detected in Williams Syndrome by FISH analysis?
7q11.23 deletion (elastin gene)
168
Which of the following is NOT a typical facial feature of Williams Syndrome?
A) Wide mouth
B) Wide spaced teeth
C) Depressed nasal bridge
D) Prominent forehead
D) Prominent forehead
169
True or False:
Failure to thrive and hypotonia are common early presentations in Williams Syndrome.
True
170
What test is used to monitor hypercalcemia in Williams Syndrome?
Urine spot Ca/Creatinine ratio and serum calcium.
## footnote
It causes painless hematuria
171
Which of the following eye findings is characteristic of Williams Syndrome?
A) Brushfield spots
B) Stellate iris pattern
C) Microphthalmia
D) Retinoblastoma
B) Stellate iris pattern
172
Why should blood pressure be monitored at every well-child visit in patients with Williams Syndrome?
Due to the risk of hypertension secondary to vascular abnormalities.
173
Which of the following genetic abnormalities causes WAGR Syndrome?
A) 22q11.2 deletion
B) 11p13 deletion
C) 7q11.23 deletion
D) Trisomy 18
B) 11p13 deletion
174
True or False:
Patients with WAGR Syndrome have a 50% risk of developing Wilms tumor.
True
175
What major eye anomaly is characteristic of WAGR Syndrome?
Aniridia (absence of the iris)
176
Which of the following is NOT a typical genitourinary anomaly in WAGR Syndrome?
A) Hypospadias
B) Cryptorchidism
C) Enlarged scrotum
D) Small penis
C) Enlarged scrotum
177
Intellectual disability is a common feature of WAGR Syndrome.
True
178
Name the tumor associated with WAGR Syndrome.
Wilms tumor
179
Which gene is involved in the pathogenesis of aniridia in WAGR Syndrome?
A) PAX6
B) ELN
C) PTPN11
D) FGFR3
A) PAX6
180
What is the genetic cause of Alagille Syndrome?
• Microdeletion of 20p12
• Mutation in the JAG1 gene
181
Which organs are primarily affected in Alagille Syndrome?
• Liver
• Heart
• Eyes
• Bones
182
What is the main liver manifestation in Alagille Syndrome?
Jaundice due to bile duct abnormalities
183
What are the common cardiac defects seen in Alagille Syndrome?
• Peripheral pulmonary stenosis
• Tetralogy of Fallot
184
What is the hallmark ocular finding in Alagille Syndrome?
Posterior embryotoxon
185
What is the characteristic bone abnormality in Alagille Syndrome?
Butterfly hemivertebrae
186
What is the most common congenital heart defect in DiGeorge syndrome?
Tetralogy of Fallot.
187
What is DiGeorge Syndrome also known as?
Velocardiofacial (VCF) syndrome.
22q11.2- deletion syndrome
188
What is the mnemonic for the features of DiGeorge syndrome?
CATCH 22
• C: Cardiac defects
• A: Abnormal facies
• T: Thymic aplasia (leading to immunodeficiency)
• C: Cleft palate
• H: Hypocalcemia (due to hypoparathyroidism)
## footnote
Other Clinical Features:
• Short stature
• Behavioral problems
• Immunodeficiency (due to thymic hypoplasia/aplasia)
189
What genetic test confirms DiGeorge syndrome?
• FISH (Fluorescence In Situ Hybridization)
• Array Comparative Genomic Hybridization (aCGH)
## Footnote:
• FISH can directly detect the microdeletion at 22q11.2.
• aCGH is more sensitive for detecting small deletions or duplications across the genome.
190
Which of the following is not typically associated with DiGeorge syndrome?
A) Hypocalcemia
B) Immunodeficiency
C) Hyperthyroidism
D) Tetralogy of Fallot
C) Hyperthyroidism
191
What is the genetic mutation responsible for achondroplasia?
Mutation in the FGFR3 gene on chromosome 4 (4p16.3).
## footnote
• FGFR3 mutation results in impaired cartilage growth and bone development, leading to disproportionate short stature.
192
What is the inheritance pattern of achondroplasia?
Autosomal Dominant (AD), but often due to a random new mutation.
193
Which of the following is a characteristic feature of achondroplasia?
A) Microcephaly
B) Long limbs
C) Mid-facial hypoplasia
D) Abnormal trunk proportion
C) Mid-facial hypoplasia
194
Which of the following neurological complications is associated with foramen magnum stenosis in achondroplasia?
A) Epilepsy
B) Quadriparesis
C) Ataxia
D) Bell’s palsy
B) Quadriparesis
195
At what point is motor developmental delay usually noticed in achondroplasia?
A) 0–2 months
B) 3–6 months
C) 7–12 months
D) After 1 year
B) 3–6 months
196
(True/False):
Growth hormone therapy can completely normalize adult height in achondroplasia.
False
197
Which of the following interventions is considered elective for height increase in achondroplasia?
A) Foramen magnum decompression
B) Limb lengthening
C) Ventriculoperitoneal shunt
D) Tonsillectomy
B) Limb lengthening
198
What is the genetic mutation responsible for Marfan syndrome?
A) FGFR3 mutation
B) FBN1 mutation
C) JAG1 mutation
D) PAX6 mutation
B) FBN1 mutation
199
Marfan syndrome follows which pattern of inheritance?
A) Autosomal recessive
B) Autosomal dominant
C) X-linked recessive
D) Mitochondrial
B) Autosomal dominant
200
Approximately what percentage of Marfan syndrome cases are due to a new mutation?
A) 10%
B) 25%
C) 50%
D) 75%
B) 25%
201
Which of the following is the most common cause of death in Marfan syndrome?
A) Mitral valve prolapse
B) Pneumothorax
C) Aortic dissection
D) Heart failure
C) Aortic dissection
202
(True/False):
Marfan syndrome affects boys more than girls.
False (affects both equally)
203
Which of the following clinical findings is NOT typical in Marfan syndrome?
A) Dislocated lens
B) Lax joints
C) Short stature
D) Long fingers
C) Short stature
204
What is the name of the diagnostic criteria used for Marfan syndrome?
A) Ghent criteria
B) Boston criteria
C) Philadelphia criteria
D) Chicago criteria
A) Ghent criteria
205
In the Revised Ghent criteria, diagnosis of Marfan syndrome is based on which of the following? (Select all that apply)
• Aortic root dilatation
• Ectopia lentis
• Systemic score points
• Identified FBN1 mutation
All of them are correct
206
Which of the following is part of Marfan syndrome management?
A) Beta-blockers
B) Steroids
C) Growth hormone
D) Limb lengthening
A) Beta-blockers
207
(True/False):
An echocardiogram should be done every 6 months to 1 year in Marfan syndrome.
True
208
Which genes are commonly mutated in Ehlers-Danlos syndrome?
A) FBN1
B) COL5A1 or COL5A2
C) FGFR3
D) JAG1
B) COL5A1 or COL5A2
209
What is the mode of inheritance of Ehlers-Danlos syndrome?
A) Autosomal recessive
B) Autosomal dominant
C) X-linked recessive
D) Mitochondrial
B) Autosomal dominant
210
Which of the following is a hallmark clinical feature of Ehlers-Danlos syndrome?
A) Short fingers
B) Marked skin extensibility
C) Macrocephaly
D) Supravalvular aortic stenosis
B) Marked skin extensibility
211
What is a frequent complication related to skin in patients with Ehlers-Danlos syndrome?
A) Hyperpigmentation
B) Frequent lacerations and scarring
C) Atopic dermatitis
D) Hypopigmented patches
B) Frequent lacerations and scarring
212
Which musculoskeletal feature is commonly associated with Ehlers-Danlos syndrome?
A) Joint hypermobility
B) Fixed joint contractures
C) Muscle weakness
D) Short limbs
A) Joint hypermobility
213
Which of the following spinal deformities can be seen in Ehlers-Danlos syndrome?
A) Kyphoscoliosis
B) Lumbar lordosis
C) Ankylosing spondylitis
D) Straight back syndrome
A) Kyphoscoliosis
214
Which cardiovascular complication is associated with Ehlers-Danlos syndrome?
A) Mitral valve prolapse
B) Aortic root dilatation
C) Supravalvular aortic stenosis
D) Interrupted aortic arch
B) Aortic root dilatation
215
What are the most commonly mutated genes in Osteogenesis Imperfecta?
A) FBN1
B) COL1A1 or COL1A2
C) FGFR3
D) PTPN11
B) COL1A1 or COL1A2
216
What is the inheritance pattern of Osteogenesis Imperfecta?
A) Autosomal recessive
B) Autosomal dominant
C) X-linked dominant
D) Mitochondrial inheritance
B) Autosomal dominant
217
Which clinical finding is classically associated with Osteogenesis Imperfecta?
A) Blue sclera
B) Hyperextensible skin
C) Cutis aplasia
D) Café au lait spots
A) Blue sclera
218
Which type of Osteogenesis Imperfecta is considered lethal?
A) Type I
B) Type II
C) Type III
D) Type IV
B) Type II
219
Which of the following is NOT typically seen in Osteogenesis Imperfecta?
A) Multiple fractures
B) Hearing loss
C) Dentinogenesis imperfecta
D) Hypotonia
D) Hypotonia
220
What is the diagnostic method for confirming Osteogenesis Imperfecta?
A) FISH analysis
B) Direct sequencing of COL1A1 or COL1A2 genes
C) Karyotyping
D) Serum calcium levels
B) Direct sequencing of COL1A1 or COL1A2 genes
221
What is the mainstay of treatment for Osteogenesis Imperfecta?
A) Growth hormone therapy
B) Cyclic IV bisphosphonate therapy (e.g., pamidronate)
C) Beta-blockers
D) Antiepileptic medications
B) Cyclic IV bisphosphonate therapy (e.g., pamidronate)
222
Which supplementations are recommended in the management of Osteogenesis Imperfecta?
A) Iron and folate
B) Vitamin D, calcium, and phosphorus
C) Magnesium and potassium
D) Vitamin B12 and zinc
B) Vitamin D, calcium, and phosphorus
223
A newborn presents with hypotonia, up-slanted palpebral fissures, and a single transverse palmar crease. What is the most likely diagnosis?
Down syndrome.
## Footnote:
Down = Most common cause of intellectual disability + congenital heart defects (AV canal).
224
Which syndrome is associated with rocker bottom feet, overlapping fingers, and VSD?
Edwards Syndrome
## Footnote:
Trisomy 18 = Fatal within first year + Micrognathia.
225
Microphthalmia, holoprosencephaly, and postaxial polydactyly are key features of which syndrome?
Patau Syndrome
## Footnote:
Trisomy 13 = Least common and most severe trisomy.
226
What is the diagnosis for a tall adolescent boy with gynecomastia, hypogonadism, and a 47,XXY karyotype?
Klinefelter Syndrome (47,XXY)
## Footnote:
Klinefelter = Tall stature + Infertility + Gynecomastia.
227
A teenage boy presents with intellectual disability, macroorchidism, and large ears. What is the most likely diagnosis?
Fragile X Syndrome
228
A short girl with webbed neck, lymphedema, and coarctation of the aorta. What syndrome is most likely?
Turner Syndrome
## Footnote:
Turner = 45,X karyotype + Short stature + Infertility.
229
A boy presents with short stature, webbed neck, pulmonary stenosis, and cryptorchidism. What syndrome fits best?
Noonan Syndrome
## Footnote:
Noonan = Turner-like in males and females (AD, PTPN11 mutation).
230
Friendly personality, supravalvular aortic stenosis, and hypercalcemia suggest which syndrome?
Williams Syndrome
## Footnote:
Williams = 7q11.23 deletion (Elastin gene).
231
A child with Wilms tumor, aniridia, and genitourinary abnormalities most likely has what syndrome?
WAGR Syndrome
## Footnote:
WAGR = 11p13 deletion (PAX6, WT1 genes).
232
A child with Wilms tumor, aniridia, and genitourinary abnormalities most likely has what syndrome?
WAGR Syndrome
## Footnote:
WAGR = 11p13 deletion (PAX6, WT1 genes).
233
A child with jaundice, peripheral pulmonary stenosis, posterior embryotoxon, and butterfly vertebrae. What is the diagnosis?
Alagille Syndrome
## Footnote:
Alagille = JAG1 mutation, liver/cardiac/eye/bone involvement.
234
A newborn with tetralogy of Fallot, thymic hypoplasia, cleft palate, and hypocalcemia. What syndrome?
DiGeorge Syndrome (22q11.2 deletion)
## Footnote:
DiGeorge = CATCH-22 (Cardiac, Abnormal facies, Thymic hypoplasia, Cleft, Hypocalcemia).
235
Short stature with trident hands, macrocephaly, and frontal bossing is characteristic of what genetic condition?
Achondroplasia
## Footnote:
Achondroplasia = FGFR3 mutation (AD, chromosome 4).
236
A tall patient with lens dislocation, aortic root dilatation, and scoliosis most likely has?
Marfan Syndrome
## Footnote: Marfan = FBN1 mutation (AD, connective tissue disorder).
237
Which syndrome presents with hyperextensible skin, hypermobile joints, and easy bruising?
Ehlers-Danlos Syndrome
## Footnote: Ehlers-Danlos = COL5A1/COL5A2 mutation (AD, connective tissue fragility).
238
A child with blue sclera, recurrent fractures, and dentinogenesis imperfecta likely has?
Osteogenesis Imperfecta
## Footnote:
Osteogenesis Imperfecta = COL1A1/COL1A2 mutations (Type I mild, Type II lethal).
239
Which of the following are energy source disorders?
A) Fatty acid oxidation disorders
B) Sugar metabolism disorders (glucose, galactose, fructose)
C) Protein metabolism disorders (organic acidemias, aminoacidopathies, urea cycle disorders)
D) All of the above
D) All of the above
240
Which of the following is an Organic Acidemia?
A) Maple syrup urine disease
B) Methylmalonic acidemia
C) Phenylketonuria
D) Homocystinuria
B) Methylmalonic acidemia
241
Give examples of Aminoacidopathies
• Maple syrup urine disease (MSUD)
• Phenylketonuria (PKU)
• Homocystinuria
242
Which of the following disorders is related to Urea Cycle Defects?
A) Ornithine transcarbamylase deficiency (OTC)
B) Glutaric acidemia
C) Phenylketonuria
D) Maple syrup urine disease
A) Ornithine transcarbamylase deficiency (OTC)
243
What are Inborn Errors of Metabolism (IEM)?
Genetic disorders caused by single-gene defects affecting specific enzymes.
244
Are IEM individually common?
No.
## footnote
They are individually rare but relatively common as a group.
245
What is the most common inheritance pattern for IEM?
A) Autosomal dominant
B) X-linked
C) Autosomal recessive
D) Mitochondrial inheritance
C) Autosomal recessive
246
Which of the following disorders is X-linked?
A) Phenylketonuria
B) Ornithine transcarbamylase deficiency (OTC)
C) Maple syrup urine disease
D) Homocystinuria
B) Ornithine transcarbamylase deficiency (OTC)
247
What clinical features suggest a metabolic disorder?
• Poor feeding
• Lethargy
• Vomiting
• Seizures or coma
## footnote
seizures not responsive to IV glucose or calcium.
248
What should you check immediately if you suspect a metabolic disorder?
Ammonia level
249
If a patient has high ammonia levels, what disorders should be considered?
A) Urea cycle disorders
B) Organic acidemias
C) Both A and B
D) Aminoacidopathies
C) Both A and B
250
If ammonia is normal but metabolic symptoms are present, which conditions are more likely?
A) Organic acidemias
B) Aminoacidopathies
C) Galactosemia
D) Both B and C
D) Both B and C
251
A 15-month-old girl presents with acute weakness, lethargy, low glucose (45 mg/dL), high ammonia (57), CO2 (5), and severe metabolic acidosis (pH 7.02, HCO3 4.8). What is the most likely cause?
A:
A) Urea cycle disorder
B) Organic acidemia
C) Galactosemia
D) Aminoacidopathy
B) Organic acidemia
252
What acid-base disturbance is seen in Organic Acidemias?
High anion gap metabolic acidosis with normal or high ammonia.
253
Which acid-base pattern suggests Urea Cycle Disorders?
A) High anion gap metabolic acidosis
B) Respiratory alkalosis with normal anion gap
C) Normal pH
D) Respiratory acidosis
B) Respiratory alkalosis with normal anion gap
254
What acid-base disturbance is expected in Aminoacidopathies or Galactosemia?
Normal anion gap metabolic disturbance.
255
What are key investigations for suspected Organic Acidemia?
• Urine organic acids
• Plasma amino acids
• Plasma acylcarnitines
256
Name two major types of Organic Acidemia.
• Propionic Acidemia
• Methylmalonic Acidemia
257
What are the common laboratory findings in Organic Acidemias?
• High anion gap metabolic acidosis
• High urine ketones
• Mild to moderate hyperammonemia
258
Which enzyme defect corresponds to each Organic Acidemia?
A) Propionic Acidemia → Propionyl CoA carboxylase
B) Methylmalonic Acidemia → Methylmalonyl CoA mutase
C) Both A and B are correct
D) Neither
C) Both A and B are correct
259
Both Propionic and Methylmalonic Acidemia typically present with:
A) High anion gap metabolic acidosis
B) Normal anion gap
C) Respiratory alkalosis
D) Hypernatremia
A) High anion gap metabolic acidosis
260
What are the shared laboratory features between Propionic and Methylmalonic Acidemia?
• High anion gap metabolic acidosis
• High urine ketones
• Mild to moderate hyperammonemia
261
Which of the following best differentiates Propionic from Methylmalonic Acidemia?
A) Enzyme involved: Propionyl CoA carboxylase vs Methylmalonyl CoA mutase
B) Presence of hypoglycemia only in Propionic
C) No metabolic acidosis in Methylmalonic
D) Normal ammonia in both
A) Enzyme involved: Propionyl CoA carboxylase vs Methylmalonyl CoA mutase
262
What is the general management approach for both Propionic and Methylmalonic Acidemia?
• Dextrose 10% infusion with electrolytes
• Correct metabolic acidosis
• Temporary protein restriction
• Provide IV lipid emulsion for calories
• Dialysis if critically ill
263
What are the key investigations for suspected Organic Acidemia?
• Urine organic acids
• Plasma amino acids
• Plasma acylcarnitines
264
What is Glutaric Acidemia Type I (GAI)?
A cerebral type of organic acidemia due to defect in glutaryl CoA dehydrogenase.
265
What are the clinical features of Glutaric Acidemia Type I?
• Macrocephaly
• Risk of subdural hematomas (can mimic child abuse)
• Basal ganglia injury during catabolic crisis
266
How is Glutaric Acidemia Type I diagnosed?
A) High plasma lactate
B) High urine glutaric acids
C) High plasma ammonia
D) High serum glucose
B) High urine glutaric acids
267
Why is Glutaric Acidemia Type I difficult to diagnose?
Because metabolites can be normal between metabolic crises.
268
What enzyme deficiency causes Phenylketonuria (PKU)?
A:
A) Phenylalanine hydroxylase
B) Branched-chain α-ketoacid dehydrogenase
C) Homocystine β-synthetase
D) Glutaryl CoA dehydrogenase
A) Phenylalanine hydroxylase
269
What is the typical clinical presentation of Phenylketonuria (PKU)?
• Fair skin and hair
• Eczema (including atopic dermatitis)
• Light sensitivity
• Hair loss
• Musty or mousy odor
270
What is the recommended dietary treatment for Phenylketonuria (PKU)?
A) Phenylalanine restriction
B) Tyrosine supplementation
C) Both A and B
D) High-protein diet
C) Both A and B
271
What severe condition can occur if Phenylketonuria (PKU) is left untreated?
• Intellectual disability
• Epilepsy
• Eye abnormalities (hypopigmentation)
• Permanent brain injury and cognitive dysfunction
272
Which of the following is a key clinical feature of Homocystinuria?
A:
A) Tall stature and osteoporosis
B) Light sensitivity
C) Eczema and hair loss
D) Musty or mousy odor
A) Tall stature and osteoporosis
273
What is the treatment for Homocystinuria?
• Betaine (to decrease homocystine levels)
• Aspirin (to prevent stroke)
• Dietary methionine restriction
• B12, folic acid, pyridoxine supplementation
274
Which condition is caused by a defect in cystathionine β-synthetase?
A:
A) Homocystinuria
B) Phenylketonuria
C) Maple Syrup Urine Disease
D) Methylmalonic Acidemia
A) Homocystinuria
275
Which of the following is a key feature that differentiates Homocystinuria from Marfan syndrome?
A:
A) Intellectual disability in Homocystinuria, normal intelligence in Marfan syndrome
B) Aortic dilatation in Homocystinuria, no aortic issues in Marfan syndrome
C) Dislocated lens in Marfan syndrome is upward, whereas in Homocystinuria it is downward
D) Limited joint mobility in Marfan syndrome, no joint limitations in Homocystinuria
A) Intellectual disability in Homocystinuria, normal intelligence in Marfan syndrome
276
Which of the following is common in all three of Maple Syrup Urine Disease (MSUD), Phenylketonuria (PKU), and Homocystinuria?
A:
A) Elevated amino acid levels in blood/urine
B) Intellectual disability if untreated
C) Musty or mousy odor in urine
D) All of the above
B) Intellectual disability if untreated
277
Which of the following best describes the key differences between Maple Syrup Urine Disease (MSUD), Phenylketonuria (PKU), and Homocystinuria?
A:
A) MSUD is caused by branched-chain α-ketoacid dehydrogenase deficiency, PKU by phenylalanine hydroxylase deficiency, and Homocystinuria by cystathionine β-synthetase deficiency.
B) PKU presents with musty odor, MSUD with hair loss, and Homocystinuria with light sensitivity.
C) All three diseases require the same treatment of methionine restriction.
D) All diseases result in a normal aorta.
A) MSUD is caused by branched-chain α-ketoacid dehydrogenase deficiency, PKU by phenylalanine hydroxylase deficiency, and Homocystinuria by cystathionine β-synthetase deficiency.
278
What is the **common clinical presentation** across Maple Syrup Urine Disease (MSUD), Phenylketonuria (PKU), and Homocystinuria if left untreated?
• Intellectual disability
• Cognitive dysfunction
• Seizures (in MSUD and PKU)
• Risk of thromboembolism (in Homocystinuria)
279
What is the main function of the urea cycle?
A) Convert ammonia into urea for renal excretion
B) Synthesize amino acids
C) Break down glucose into energy
D) Convert fatty acids into glucose
A) Convert ammonia into urea for renal excretion
280
What is the clinical presentation of Urea Cycle Disorders in newborns?
• Neonatal lethargy
• Vomiting
• Coma
• Death
• Hyperammonemia without acidosis
281
Which of the following is a common laboratory finding in Urea Cycle Disorders?
A) Very high ammonia levels
B) Very high blood urea nitrogen (BUN) levels
C) High plasma glucose levels
D) Low creatinine levels
A) Very high ammonia levels
282
What is the main clinical manifestation caused by hyperammonemia in Urea Cycle Disorders?
• Cerebral edema
• Altered mental status
• Lethargy
• Vomiting
• Coma and death
283
Which of the following disorders is characterized by a deficiency in Ornithine Transcarbamylase?
A) Ornithine Transcarbamylase Deficiency (OTC)
B) Citrullinemia
C) Argininosuccinic aciduria
D) Maple Syrup Urine Disease
A) Ornithine Transcarbamylase Deficiency (OTC)
284
What are the typical findings in the laboratory for Ornithine Transcarbamylase Deficiency (OTC)?
• Elevated ammonia levels
• Relatively low citrulline levels
• Elevated orotic acid levels in urine
• Low ornithine, glutamine, and alanine levels
285
Which of the following **is NOT** used for newborn screening of Ornithine Transcarbamylase Deficiency (OTC)?
A) Newborn screening is not done for OTC
B) Plasma amino acid analysis
C) Urine orotic acid test
D) Blood ammonia levels
A) Newborn screening is not done for OTC
286
What enzyme deficiency causes Citrullinemia?
A) Argininosuccinate synthetase
B) Ornithine transcarbamylase
C) Argininosuccinate lyase
D) Urease
A) Argininosuccinate synthetase
287
What are the characteristic findings in Citrullinemia?
• Elevated citrulline levels in blood
• Elevated argininosuccinic acid in blood and urine
• Hyperammonemia
288
What is the acute management for Citrullinemia?
• NPO (nothing by mouth)
• Dextrose (10% with salt)
• Early use of fluids
• Sodium benzoate/Arginine
• Dialysis
289
Which enzyme is deficient in Argininosuccinic Aciduria?
A:
A) Argininosuccinate lyase
B) Argininosuccinate synthetase
C) Ornithine transcarbamylase
D) Carbamoyl-phosphate synthetase
A) Argininosuccinate lyase
290
What are the key features of Argininosuccinic Aciduria?
• Elevated argininosuccinate acid in blood and urine
• Hyperammonemia
• Citrulline levels may be normal or elevated
291
What is the chronic management of Argininosuccinic Aciduria?
• Low-protein diet
• Supplementation with phenylbutyrate, arginine, or citrulline
• Liver transplantation
292
Which of the following is a key difference between Ornithine Transcarbamylase Deficiency (OTC), Citrullinemia, and Argininosuccinic Aciduria?
A:
A) OTC shows low citrulline, while Citrullinemia and Argininosuccinic Aciduria show high citrulline levels.
B) Citrullinemia and OTC have elevated orotic acid levels in urine, but Argininosuccinic Aciduria does not.
C) Argininosuccinic Aciduria shows high levels of ammonia but not in Citrullinemia.
D) All three disorders have normal ammonia levels.
A) OTC shows low citrulline, while Citrullinemia and Argininosuccinic Aciduria show high citrulline levels.
293
What is the main issue in Fatty Acid Oxidation Disorders (FAOD)?
A) Inability to metabolize fatty acids during prolonged fasting
B) Inability to metabolize glucose
C) Inability to produce urea
D) Inability to digest proteins
A) Inability to metabolize fatty acids during prolonged fasting
294
What is a common clinical feature in patients with Fatty Acid Oxidation Disorders (FAOD)?
• Hypoketotic hypoglycemia
• Lethargy
• Vomiting
• Sudden infant death syndrome (SIDS)
• Reye syndrome
295
Which enzyme deficiency is commonly associated with Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCAD)?
A) Medium-Chain Acyl-CoA Dehydrogenase
B) Ornithine Transcarbamylase
C) Phenylalanine Hydroxylase
D) Argininosuccinate Lyase
A) Medium-Chain Acyl-CoA Dehydrogenase
296
Enumerate a potential long-term complications of Long-chain fatty acid oxidation disorders?
• Cardiomyopathy
• Rhabdomyolysis
• Hypoglycemia
• Hepatomegaly
297
What is the recommended treatment for Fatty Acid Oxidation Disorders (FAOD) during acute episodes?
• **Avoidance of fasting**
• Supplementation with carnitine
• Administration of dextrose
• Prevention of fasting more than 4-5 hours
298
What is an essential preventive measure for Fatty Acid Oxidation Disorders (FAOD)?
A) Avoid fasting more than 4-5 hours
B) High-protein diet
C) Avoiding carbohydrates
D) Frequent water intake
A) Avoid fasting more than 4-5 hours
299
What is the most common cause of sudden death in infants with Fatty Acid Oxidation Disorders (FAOD)?
• Sudden infant death syndrome (SIDS)
300
What percentage of babies with Fatty Acid Oxidation Disorders (FAOD) die before the results of newborn screening are available?
A) 25%
B) 50%
C) 10%
D) 75%
A) 25%
301
What is the recommended dietary management for children with Fatty Acid Oxidation Disorders (FAOD)?
• Carbohydrate snacks at bedtime
• Avoidance of fasting for long periods
302
What is the role of Carnitine in the management of Fatty Acid Oxidation Disorders (FAOD)?
A:
A) It helps in the metabolism of fatty acids during acute episodes
B) It increases the breakdown of proteins
C) It regulates glucose metabolism
D) It promotes amino acid synthesis
A) It helps in the metabolism of fatty acids during acute episodes
303
Which of the following disorders is most commonly associated with a deficiency of galactokinase?
A:
A) Galactosemia
B) McArdle disease
C) Von Gierke disease
D) Fructose intolerance
A) Galactosemia
304
What is a common clinical feature of Galactosemia caused by galactokinase deficiency?
• Cataracts
• Jaundice
• Hepatomegaly
305
Von Gierke disease results from a deficiency in which enzyme?
A:
A) Glucose-6-phosphatase
B) Galactokinase
C) Fructokinase
D) Aldolase B
A) Glucose-6-phosphatase
306
What is the main characteristic of McArdle disease?
• Deficiency of muscle glycogen phosphorylase
• Muscle cramps and exercise intolerance
• Increased blood lactate after exercise
307
What is the enzyme deficiency in Galactosemia?
A) Galactose-1-phosphate uridyltransferase (GALT)
B) Galactokinase
C) Glucose-6-phosphatase
D) Fructokinase
A) Galactose-1-phosphate uridyltransferase (GALT)
308
What is the common clinical presentation of a newborn with Galactosemia?
• Hypoglycemia
• Liver dysfunction
• Jaundice
• Coagulopathy
• Escherichia coli sepsis
• Cataracts
309
How is Galactosemia diagnosed?
A:
A) Reducing substance in urine
B) High blood glucose levels
C) Elevated bilirubin in serum
D) Elevated liver enzymes
A) Reducing substance in urine
310
Which of the following is the most appropriate treatment for Galactosemia?
A:
A) Elimination of galactose from the diet for life
B) Supplementation with galactose
C) Treatment with antibiotics for E. coli
D) High-protein diet
A) Elimination of galactose from the diet for life
311
A 2-week-old neonate boy presents with bilateral cataracts, hypoglycemia, dark urine, and pale stools. Which of the following disorders is most likely?
A) Galactosemia
B) Tay-Sachs disease
C) GSD type 1
D) Canavan disease
A) Galactosemia
312
What is a complication that may arise in neonates with Galactosemia if left untreated?
• Hepatomegaly
• Kidney damage
• Brain damage
• Cataracts
• Seizures
313
What substance accumulates in Galactosemia due to the deficiency of GALT enzyme?
• Galactose-1-phosphate (G1P)
• Galactose
• Glucose-6-phosphate
• Fructose-1,6-bisphosphate
314
Which of the following is the predisposing factor for E. coli sepsis in Galactosemia patients?
A:
A) Deficiency of GALT enzyme
B) High galactose levels
C) Hypoglycemia
D) Liver dysfunction
A) Deficiency of GALT enzyme
315
Which of the following enzymes is deficient in Von Gierke disease (Type I)?
A:
A) Glucose-6-phosphatase
B) Lysosomal α-glucosidase
C) Amylo-1,6-glucosidase
D) Phosphorylase
A) Glucose-6-phosphatase
316
Which of the following is associated with liver enlargement, hypoglycemia, and growth failure?
A) Von Gierke disease
B) Pompe disease
C) McArdle disease
A) Von Gierke disease
317
Which disease involves cardiomegaly and muscle hypotonia?
A) Cori disease
B) Pompe disease
C) McArdle disease
B) Pompe disease
318
Which disease presents with muscle weakness and cramps after exercise?
A) Von Gierke disease
B) Pompe disease
C) McArdle disease
D) Cori disease
C) McArdle disease
319
What is the main treatment for Von Gierke disease?
A) Protein restriction and glucose supplementation
B) Muscle strengthening
C) Low-fat diet and carnitine
D) High-protein diet and exercise
A) Protein restriction and glucose supplementation
320
Which disease is associated with hypoglycemia, liver enlargement, and cataracts in newborns?
A) Cori disease
B) Von Gierke disease
C) McArdle disease
D) Galactosemia
B) Von Gierke disease
321
Which of the following is **milder** and affects both muscles and liver?
A) Pompe disease
B) McArdle disease
C) Cori disease
D) Von Gierke disease
C) Cori disease
322
Pompe disease affects which organ primarily?
A) Liver
B) Muscles
C) Kidneys
D) Heart
D) Heart
323
What is the main treatment for Von Gierke disease?
A) Cornstarch supplementation
B) Muscle strengthening
C) Liver transplantation
D) Dietary restriction of proteins
A) Cornstarch supplementation
324
Which of the following MPS disorders is X-linked?
A) MPS I (Hurler)
B) MPS II (Hunter)
C) MPS III (Sanfilippo)
D) MPS IV (Morquio)
B) MPS II (Hunter)
325
In which MPS type is corneal clouding present?
A) MPS II (Hunter)
B) MPS IV (Morquio)
C) MPS I (Hurler)
D) MPS III (Sanfilippo)
C) MPS I (Hurler)
326
Which MPS disorder is associated with skeletal abnormalities like kyphosis, lordosis, and claw hands?
A) MPS II (Hunter)
B) MPS III (Sanfilippo)
C) MPS VI (Maroteaux-Lamy)
D) MPS IV (Morquio)
D) MPS IV (Morquio)
327
Developmental delay and mental retardation are features of which MPS disorders?
A) MPS II (Hunter)
B) MPS III (Sanfilippo)
C) MPS IV (Morquio)
D) MPS I (Hurler)
B) MPS III (Sanfilippo) and D) MPS I (Hurler)
328
Which of the following MPS disorders does not show heart valvular lesions?
A) MPS I (Hurler)
B) MPS II (Hunter)
C) MPS III (Sanfilippo)
D) MPS IV (Morquio)
C) MPS III (Sanfilippo)
328
Which of the following diseases is caused by a deficiency of alpha-galactosidase A?
A) Niemann-Pick disease
B) Fabry disease
C) Tay-Sachs disease
D) Gaucher disease
B) Fabry disease
329
A 5-year-old child presents with hepatosplenomegaly, progressive neurodegeneration, and cherry-red spots on the retina. What is the most likely diagnosis?
A) Gaucher disease
B) Tay-Sachs disease
C) Niemann-Pick disease
D) Fabry disease
B) Tay-Sachs disease
330
Which of the following diseases presents with acroparesthesia, angiokeratomas, and corneal opacity?
A) Niemann-Pick disease
B) Gaucher disease
C) Fabry disease
D) Metachromatic leukodystrophy
C) Fabry disease
331
Which enzyme is deficient in Gaucher disease?
A) Sphingomyelinase
B) Hexosaminidase A
C) Alpha-galactosidase A
D) Beta-glucosidase
D) Beta-glucosidase
332
In which disease is enzyme replacement therapy available as a treatment?
A) Tay-Sachs disease
B) Gaucher disease
C) Niemann-Pick disease
D) Metachromatic leukodystrophy
B) Gaucher disease
333
Which of the following diseases presents with progressive neurodegeneration and spasticity, with death occurring by the age of 7 years?
A) Gaucher disease
B) Niemann-Pick disease
C) Tay-Sachs disease
D) Fabry disease
B) Niemann-Pick disease
334
Which sphingolipidosis is associated with a deficiency of sphingomyelinase?
A) Tay-Sachs disease
B) Niemann-Pick disease
C) Gaucher disease
D) Metachromatic leukodystrophy
B) Niemann-Pick disease
335
A child with hepatosplenomegaly, pancytopenia, and bone pain is most likely suffering from:
A) Tay-Sachs disease
B) Niemann-Pick disease
C) Gaucher disease
D) Fabry disease
C) Gaucher disease
336
Which of the following is the most likely diagnosis for a child with dysmorphic facial features, seizures, liver disease, and profound hypotonia, with a characteristic abnormality in myelination on brain MRI?
A) Zellweger syndrome
B) Adrenoleukodystrophy
C) Gaucher disease
D) Niemann-Pick disease
A) Zellweger syndrome
337
A patient presents with developmental regression, spasticity, and new-onset adrenal failure. Initial screening reveals a defect in the peroxisomal oxidation of very long-chain fatty acids (VLCFAs). What is the most likely diagnosis?
A) Zellweger syndrome
B) Adrenoleukodystrophy
C) Tay-Sachs disease
D) Fabry disease
B) Adrenoleukodystrophy
338
Which of the following features is characteristic of Zellweger syndrome?
A) Adrenal failure and spasticity
B) Seizures, hearing and vision deficits, and leukodystrophy on MRI
C) Cherry-red spots on the retina
D) Bone deformities and hepatosplenomegaly
B) Seizures, hearing and vision deficits, and leukodystrophy on MRI
339
Which screening test is typically used to diagnose Zellweger syndrome and Adrenoleukodystrophy?
A) Blood ammonia levels
B) Plasma VLCFA analysis
C) Brain MRI
D) Enzyme activity assay
B) Plasma VLCFA analysis
340
In which disorder is adrenal failure a hallmark feature, typically seen in school-age boys?
A) Zellweger syndrome
B) Adrenoleukodystrophy
C) Tay-Sachs disease
D) Gaucher disease
B) Adrenoleukodystrophy
341
Which of the following is a treatment option that may prevent progression in some cases of Adrenoleukodystrophy?
A) Liver transplant
B) Enzyme replacement therapy
C) Hematopoietic stem cell transplantation (HSCT)
D) Gene therapy
C) Hematopoietic stem cell transplantation (HSCT)
