Syndromes, Genetics/Metabolism, "Other" Flashcards
(126 cards)
1
Q
Pustular melanosis and erythema toxicum microscopic findings
A
- PMNs
- Eosinophils
2
Q
Port wine stain treatment
A
Pulsed dye laser (recommended to start treatment within first year)
3
Q
Infantile hemangioma treatment
A
Often none as they involute in first few years
Treat if blocking vision or disfiguring: systemic glucocorticoid, beta blockers, laser
4
Q
PHACES syndrome clinical findings
A
Posterior fossa malformation
Hemangiomas (facial or neck)
Arterial lesions (absent MCA, persistent trigeminal artery)
Cardiac lesions (abnormal aortic arch, septal defects)
Eye (retina)
Sternal defects
5
Q
What is the difference in detection of hearing loss between OAE and ABR?
A
ABR tests for sensorineural hearing loss (OAE can’t test transmission from CN VIII to brainstem)
6
Q
Recommended time frame for a repeat hearing screen in at-risk infants
A
24-30 months (sooner if very high-risk e.g. CMV, ECMO, bad infections)
7
Q
CHARGE syndrome clinical findings
A
Coloboma
Heart defect
Atresia choanae
Restricted growth
Genital (hypoplasia)
Ear defect/deafness
Can be associated with TEF
8
Q
VACTERL syndrome clinical findings
A
Vertebral
Anorectal
Cardiac
Tracheoesophageal
Renal/GU
Limb
9
Q
Both maternal and neonatal exposure to erythromycin increases risk of _____
A
Pyloric stenosis
10
Q
Beckwith-Wiedemann syndrome clinical findings
A
- Hypoglycemia*
- Macrosomia*/hemihypertrophy (overgrowth syndrome)
- Macroglossia*
Visceromegaly (overgrowth syndrome)
Hydronephrosis/renal issues
Predisposition to infantile tumors
11
Q
Schwachman-Diamond syndrome triad
A
Failure to thrive Pancreatic insufficiency Bone marrow failure (most notably neutropenia but can be all three)
12
Q
Schwachman-Diamond mutation
A
7q11
13
Q
Cystic fibrosis clinical manifestations
A
Meconium ileus (worst cases have a pseudocyst or peritonitis)
Failure to thrive
Pancreatic insufficiency
Later severe respiratory infections/insufficiency
14
Q
OEIS complex/syndrome clinical findings
A
All related to failure to ventral walls to fuse Omphalocele Exstrophy (cloaca or variant where bladder and rectum are exposed and not fully formed) Imperforate anus Spinal defects (e.g. spina bifida)
15
Q
EEC syndrome clinical findings
A
Ectodermal dysplasia (skin, hair, teeth, nails)
Ectrodactyly (“split hand” where central digits are missing)
Cleft palate
When you have EEC it’s EASY to C, it’s on your face and hands
16
Q
Pentalogy of Cantrell physical findings
A
Sternal defect
Diaphragmatic defect (anterior)
Absent lower pericardium
Cardiac defect (usually VSD; can involve ectopia cordis –wrongly placed and partially/completely exposed heart)
Abdominal wall defect (hernia, omphalocele)
17
Q
The primary finding in former premature infants who received high doses of morphine
A
Smaller cerebellums (in animal models, induces cerebellar apoptosis) Worse neurodevelopmental outcomes (NDO) is NOT definitively proven
18
Q
Name three endocrine or metabolic disorders that present with cholestasis
A
Gaucher disease
Niemann-Pick type C
Wolman disease
Tyrisonemia
Galactosemia
Lysosomal acid lipase (LAL) deficiency
19
Q
Hallmarks of glycogen storage diseases
A
Skeletal and cardiac muscle dysfunction due to glycogen accumulation
(Will have elevated creatine kinase, systolic dysfunction)
20
Q
Cause of Pompeii disease
A
Acid alpha-glucosidase deficiency (GAA deficiency 2-2 mutation on 17q25)
i.e. Glycogen storage disease (type II)
Treatment is every-other-week GAA enzyme replacement therapy
21
Q
_______ has similar manifestations to Turners Syndrome but a normal karyotype/microarray
A
Noonan Syndrome
Findings include: nuchal translucency/redundancy, low-set ears, lymphedema, pulmonary stenosis
Later have: hypotonia/delayed motor, mild intellectual disability (especially speech), occasionally poor growth
22
Q
Most common cause of Noonan Syndrome
A
Usually due to gain of function mutation in the RAS-mitogen–activated protein kinase (MAPK) signal transduction pathway
AKA “RASopathies”, requires specific panel (not detected on conventional CMA)
23
Q
Gene associated with CHARGE syndrome
A
CHD7 (chromodomain helicase DNA-binding protein)
Therefore, single gene sequencing is best test
24
Q
Synonym for chromosomal microarray
A
Comparative genomic hybridization (CGH)
Good for mutations down to 50kb, but smaller deletions or single-point mutations not detected
25
What are variant-specific assays good for?
Diseases where a known of set of mutations are most commonly associated with the disease
e.g. cystic fibrosis
26
What are next-generation sequencing (multigene) panel tests good for?
Broad phenotypic diseases that have multiple genetic causes, so multiple genes are simultaneously sequenced off of one sample
e.g. cholestasis panel, epilepsy panel
27
Most common type of heat loss immediately after birth
Evaporative--reason drying is critical first step in resuscitation
(Others are conductive, convective and radiant--extrapolate from cooking terminology)
28
Most common form of heat loss (after birth/resuscitation)
Radiant--heat following gradiant, radiates from warm infant to cooler surroundings
(Others are convective, conductive, evaporative--think of them like cooking terminology)
29
Most common type of epidermolysis bullosa and the layer of skin it involves
Epidermolysis bullosa simplex--epidermis (other phrasings: "intraepidermal", dermoepidermal layer--AKA most shallow of types)
(No scarring, rarely mucosal involvement)
(aad.org)
30
What's the level of skin where shearing occurs in junctional epidermolysis bullosa? What other problems typically occur?
Lamina lucida, between epidermis and dermis (AKA the _junction_ between layers)
Dystrophic/absent nails, involvement of other systems with mucosa (eyes, GI, GU, respiratory), IF severe form then high mortality rate
31
The most classic "severe" form of epidermolysis bullosa and the layer of skin involved
**_D_**ystrophic epidermolysis bullosa, **_D_**eep in **_D_**ermis
(collagen VII issues, which would normally form the anchoring fibrils extending from dermis into the basement membrane zone)
32
If blistering i.e. bullae are present after 1-2 weeks of life, what other finding might help determine if the cause is genetic or infectious?
Dystrophic/absent nails, involvement of mucosa--point toward epidermolysis bullosa (either JEB or DEB)
Staphylococcal scalded skin--the main infectious differential--does not include either of these
33
Name three genetic disorders that demonstrate "anticipation" (AKA repeat disorders)
1. Huntington's
2. Myotonic dystrophy (worst if from maternal)
3. Fragile X
34
Three classic autosomal dominant Mendelian trait disorders
1. Achondroplasia (FGFR3, most de novo)
2. Neurofibromatosis
3. Tuberous sclerosis
To be Mendelian need to be single-gene
35
All inborn errors of metabolism are autosomal recessive except _______ (two), which follow _________ inheritance pattern
1. OTCD (a urea cycle defect)
2. Hunter syndrome (glycogen storage; remember Hunter like a *male*)
3. X-linked recessive
(Adrenoleukodystrophy is also X-linked recessive)
36
Three groups of protein metabolic disorders and their causes
1. Organic acidemias: inability to completely breakdown branched AAs, causing accumulation of byproducts
2. Amino acidopathies: deficient enzyme causes accumulation of INTACT amino acids
3. Urea cycle disorders: inability to make urea from nitrogen, causes accumulation of ammonia
* Because of these, OAs and UCDs cause hyperammonemia but OAs have acidosis and UCDs do not*
37
Hallmark findings of organic acidemias
1. Anion-gap metabolic acidosis
2. Hyperammonemia
3. High urine organic acids
e. g. methylmalonic acidemia, propionic acidemia
38
Hallmark findings of urea cycle disorders
1. Respiratory ALKAlosis
2. Hyperammonemia
e. g. OTCD, citrullinemia, argininemia
39
Hallmark findings of aminoacidopathies
1. normal pH
2. normal ammonia
3. elevated SPECIFIC plasma amino acid
e. g. MSUD, PKU, Tyrosinemia, Nonketotic Hyperglycinemia
40
Hallmark findings of fatty acid oxidation disorders
1. Metabolic acidosis with HIGH lactate
2. Low glucose
3. Inappropriately low ketones (despite hypoglycemia)
3. High creatine phosphokinase (CPK) and uric acid
e. g. MCAD, VLCAD, Smith-Lemli-Opitz
41
What are the clinically important essential amino acids
1. phenylalanine--even with PKU need *some* in diet
2. branched: isoleucine, leucine, valine--organic acidemias are results of inability to break these down (as is maple syrup urine disease)
(full list: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine)
42
Main IEM group with respiratory alkalosis
Urea cycle disorders
Their hyperammonemia tends to be more impressive with an absent or very mild metabolic acidosis and respiratory alkalosis
43
Two IEM groups that can have abnormal urine organic acids
Organic acidemias and fatty acid oxidation defects
44
Genetic mutation and inheritance for incontinentia pigmenti
NEMO, X-linked *dominant*
If you're a male fetus with incontinentia pigmenti, you're *sleeping with the fishes like NEMO*
(lethal in males)
45
Genetic mutation and inheritance for achondroplasia
FGFR3, autosomal dominant
Almost all are de novo thus does not "appear" AD
46
All IEM are autosomal _______ except \_\_\_\_\_, \_\_\_\_\_\_\_, and \_\_\_\_\_, which are X-linked.
1. Recessive
2. OTCD (ornithine transcarbomylase deficiency)
3. Hunter's syndrome (glycogen storage disorder)
4. X-linked adrenoleukodystrophy
47
Name five commonly tested amino acidopathies and how they generally present
1. PKU (phenylketonuria)
2. MSUD (maple syrupe urine disease)
3. Transient tyrosinemia
4. Nonketotic hyperglycinemia
5. Homocystinuria
Neurologic manifestations (lethargy, apnea, seizures, or just disability) without much acidosis
48
What is the most common organ system affected by amino acidopathies
Nervous system (many of the metabolites built up can cross blood-brain barrier and are toxic)
49
Facts for Phenylketonuria (PKU)
1. Asymptomatic in newborn period
2. Elevated phenylalinine (and Phe/Tyr ratio)
3. Phenylalanine is an essential AA so can't completely eliminate
4. Poor control in PKU mom causes microcephaly/cognitive impairment and CHD
* Amino Acidopathy*
50
Facts for Transient Tyrosinemia of the Newborn (another TTN!)
1. Most common amino acid "disorder" in preemies
2. Inadequate maturation of 4-hydroxyphenylpyruvate dioxygenase
3. Tyrosine can be *crazy* high, just protein restrict x4-6 weeks
* Amino Acidopathy*
51
How can you distinguish between Transient Tyrosinemia and Tyrosinemia Type 1
TT1 has elevated urine succinylacetone
*It SUCKS ASS to have real Tyrosinemia because it affects so many organs*
(TT1 is symptomatic and TTN is not--hepatic failure, Fanconi syndrome, nerve disease, hepatocarcinoma)
52
Facts for Maple Syrup Urine Disease (MSUD)
1. Can't fully breakdown branched amino acids: leucine, isoleucine, valine
2. See horrible cerebral edema (2-2 leucine), sudden lethargy and apnea
3. Remember isoleucine and valine are essentials so *must give at least some*
4. Need special diet and then liver transplant
* Amino Acidopathy*
53
Facts for Nonketotic Hyperglycinemia
1. Glycine is an excitatory neurotransmitter, so see seizures and myoclonus
2. Elevated glycine in CSF\>\>serum
3. Hemodialysis and benzoate
* Amino Acidopathy*
54
Name three commonly tested organic acidemias and their common signs
1. Methylmalonic **acidemia**
2. Propionic **acidemia**
3. Isovaleric **acidemia**
Anion-gap metabolic acidosis, *hyperammonemia*, hyperglycinemia, neutropenia/thrombocytopenia, and some elevated urine organic acid, abnormal acylcarnitine profile
(Both OA and UCD have hyperammonemia, main way to tell difference: acidosis vs UCD has alkalosis)
55
Facts for Propionic acidemia
1. Elevated propionyl carnitine *on acylcarnitine profile (deficiency is Propionyl CoA Carboxylase)*
2. Lots of overlap with some other IEM: present w/ lethargy, coma, hyperglycinemia
3. Metabolic acidosis and hyperammonemia--not present in nonketotic hyperglycinemia
4. Treat with carnitine and diet
* Organic Acidemia*
56
Facts for Methylmalonic Acidemia
1. Elevated C3 on acylcarnitine profile
2. Urine organic acid: methylmalonic acid, plasma amino acid: glycine
3. B12 deficiency can cause elevated MMA and cause false-positive on NBS
4. Treat with diet, carnitine, B12 supplement
57
What two types of IEM are diagnosed in-part with an acylcarnitine profile
Organic acidemias and fatty acid oxidation disorders
Also helps you remember which ones need carnitine supplementation
*Carnitine shuttles FAs and binds to OAs to help excretion; in OAs certain types are **low** and in FAODs certain types are **high** but in **BOTH total carnitine is low***
58
Name three commonly tested urea cycle defects and their general presenting signs
1. Ornithine transcarbamylase deficiency--X-linked
2. Citrullinemia
3. Argininemia
Respiratory alkalosis, HIGH hyperammonemia (because can't break down to urea), encephalopathy
59
Facts for OTCD (Ornithine Transcarbamylase Deficiency)
1. X-linked: think newborn male with lethargy, **hyperammonemia**
2. Urine **orotic acid**
2. Give ammonia scavenger: phenylbutyrate, benzoate (will need liver transplant)
3. Supplement arginine (becomes essential, can't get to that step in urea cycle)
* Urea Cycle Defect*
60
Key thing to think of while awaiting metabolic studies when a lethargic neonate has hyperammonemia
1. Stop protein-containing feeds/fluids
2. Studies to send: ABG, lactate, plasma amino acids, urine organic acids, CSF amino acids, acylcarnitine profile
61
Two big types of carbohydrate-related IEMs
1. Mono/Disaccharide metabolic disorders (can't break them down)
2. Glycogen storage disorders
62
Facts for Galactosemia
1. Deficient **GALT** (galactose-1-phosphate uridyltransferase)
2. **Jaundice** with direct component, **cataracts**, coagulopathy, **E. Coli sepsis**
3. Elevated galactose-1-phosphate
4. Fanconi syndrome can be part in addition to liver failure
63
Three Inborn Errors of Metabolism that present with liver failure
1. Tyrosinemia Type 1 (amino acidopathy)
2. Galactosemia (carbohydrate disorder)
3. Hereditary Fructose Intolerance (carbohydrate disorder)
***_T_**hese **_G_**uys **_H_**ate the Liver because they can't handle sugar*
64
Diagnosis: Lethargy and liver failure from starting formula
Hereditary Fructose Intolerance--some contain sucrose (glucose+fructose)
65
Name two commonly tested lysosomal storage disorders and their common signs
1. Hurler's: Mucopolysaccharidosis type I
2. Hunter's: MPS type II (X-linked)
Accumulation of glycosaminoglycans (GAGs) in lots of tissues--liver, corneas, bone (dystosis multiplex); see high urine [GAG]
66
Name the two most important subgroups of lysosomal storage disorders
1. Mucopolysaccharidoses (both lipid and glygocen buildup): Hurler's and Hunter's
2. Lipid storage: Gaucher, Niemann-Pick, Tay-Sachs (cherry-red macula)
67
Name two examples of glycogen storage diseases and their presenting signs
GSD Type 1a (Von Gierke)
GSD Type 2 (Pompe)
Hepatomegaly, cardiomyopathy, glycogen in these tissues
68
Name three commonly tested fatty acid oxidation defects and their common signs
1. MCAD
2. VLCAD
3. Smith-Lemli-Opitz
* Nonketotic hypoglycemia*, lactic acidosis, elevated creatine phosphokinase (CPK)
Hypoglycemic episodes usually in setting of illness or fasting
69
Facts for MCAD
1. Most common fatty acid oxidation defect
2. Hypoketotic hypoglycemia, abnormal acylcarnitine profile (high C10 and C8)
70
Facts for Smith-Lemli-Opitz
1. 7-dehydrocholesterol reductase mutation (7-dehydrocholesterol accumulates)
2. SEVERE intellectual disability, undeveloped male, 2-3 toe syndactyly and extra digits (CHD, down-slanting eyes
* Disorder of Cholesterol Synthesis (cholesterol needed for steroids, myelin, many other things)*
(healthjade. net)
71
Name two peroxisome disorders and their signs
Zellweger (most severe) (AKA cerebro-hepato-renal syndrome)
X-linked adrenoleukodystrophy
**High VLCFA** (C26), Intellectual disability/seizures/hypotonia, large fontanelle, hepatomegaly
*Severe forms lethal in first year*
72
Diagnosis: Ammonia 1500, high glutamine and alanin, low arginine and citrulline
Carbamyl phosphate synthetase deficiency
*Urea Cycle Defect*
Think of UCDs whenever the ammonia is **very** elevated and you see arginine decreased
73
The only urea cycle defect with elevated citrulline
Citrullinemia--arginosuccinic acid synthetase deficiency
## Footnote
*All UCDs have a low arginine, all others also have low citrulline*
74
The X-linked lysosomal storage disorder
Hunter's syndrome (Mucopolysaccharodosis type II)
## Footnote
*Hunters tend to be men*
75
Cat-eye syndrome clinical findings
Coloboma, anal atresia, hearing loss
Aneuploidy, partial 22
*Cat eye is from the coloboma*
76
Meckel gruber triad
Encephalocele
Dysplastic cystic kidneys
Postaxial polydactyly
(Lethal)
77
The "revolutionary" treatment for Tyrosinemia Type 1
NTBC: nitrotrifluoromethylbenzoyl
Inhibitor of the tyrosine catabolic pathway
(NTBC helps decrease liver failure, Fanconi syndrome and peripheral neuropathy, but many patients still get liver cancer)
78
Facts for Thrombocytopenia-Absent Radii (TAR)
1) 25% mortality 2-2 intracranial hemorrhage in first year
2) Often have congenital heart defects (ASD or TOF)
3) Absent radii but normal thumbs (unlike Fanconi anemia)
79
What is something to consider in all patients with VACTERL association
There are \>20 genetic syndrmes that overlap with it, so if ANY findings remind you of anything else or could fit another pattern, they may actually be testing you on that "overlap" syndrome
80
Which two IEMs are best distinguished by urine orotic acid
Carbamylase phosphate synthetase deficiency: LOW
Ornithine transcarbamylase deficiency: HIGH
* In **_O_**TCD, **_o_**rotic acid is **_O_**VER the top*
* Organic Acidemias*
81
Hypoglycemia when fasting/stressed is one of the hallmark features of which IEM group
Fatty acid oxidation defects
(Also think of glycogen storage defects and gluconeogenesis defects)
82
What IEM can be seen at birth and often has a h/o "hiccups" in utero
Nonketotic hyperglycinemia AKA glycine encephalopathy
(80% caused by GLDC mutations)
83
Genetic cause of Noonan Syndrome
Ras/mitogen-activated protein kinase (MAPK) signaling
(Most mutations in this pathway are gain-of-function--*thus why Noonan is autosomal dominant*)
84
Diagnosis: Low-set ears, hypertelorism, a murmur with ECG abnormalities and thrombocytopenia
Noonan Syndrome
*Classically causes pulmonic stenosis and/or hypertrophic cardiomyopathy as CHD*
(Causes are Ras-MAPK signaling mutations)
85
Identify the part of the limb(s) associated with:
Acromelia
Mesomelia
Micromelia
Rhizomelia
Acro: distal
Meso: middle
Rhizo: proximal
Micro: entire
*Recommend rearranging them this way to facilitate memorizing, start with acro as reference (acrocyanosis)*
86
Most common mechanism for aneuploidy
Meiotic nondisjunction
87
Definition of a Robertsonian translocation
Fusion of q (long) arms of two acrocentromeric chromosomes, so loss of p arms is less relevant Causes about 4% of Trisomy 21s
88
Organ systems most affected in mitochondrial disorders
Those high-energy consumers: brain, heart, kidneys, muscle
89
Maternal uniparental disomy of chromosome 15 can cause \_\_\_\_\_\_\_\_\_\_
Prader-Willi (it’s inheritance of 2 copies of maternally imprinted 15q11-13, with loss AKA “functional deletion” of any paternal 15q copy)
90
Infants with neural tube defects (NTDs) have mothers with a higher rate of _____ gene mutation
5,10-methylenetetrahydrofolate reductase (MTHFR) Having a baby with spina bifida is a MTHerF\*\*eR
91
Syndromes associated with HLHS (hypoplastic left heart syndrome)
Trisomies 13 and 18
Turner Syndrome
Jacobsen (*11q terminal deletion that mainly comes w/ neurobehavioral problems, lowset ears and hypertelorism)*
Holt-Oram (*It's hard to HOLD On with radial and cardiac defects, especially since it's auto dominant!)*
*Genes (not syndromes) also assoc. w/ HLHS: GJA1, NKX2-5, NOTCH1, HAND1*
92
Two classic trinucleotide repeat genetic disorders that can present in infancy
Fragile X and congenital myotonic dystrophy
## Footnote
*FMR1 and DMPK genes; congenital MD is autosomal dominant*
93
The leading hereditary cause of cognitive impairment
Fragile X
## Footnote
*FMR1 gene, where trinucleotide repeat \>200 confers worst phenotype AKA "true" mutation*
94
Findings associated with Neurofibromatosis-1 (AKA von Recklinghausen)
Cafe au lait macules (#1 finding in infants)
Axillary freckling
Lisch nodules *i.e. iris hamartomas*
Neurofibromas
Optic glioma
*Skeletal dysplasia (not commonly thought of)*
95
Name the IEM known for: cataracts
Galactosemia
## Footnote
* E. Coli sepsis, cataracts, (less specific: vomiting, lethargy, liver failure)*
* Enzyme: Galactose-1-phosphate-uridyltransferase (the longest named of all IEM deficiencies)*
96
Name the IEM known for: starting once FORMULA is introduced
Hereditary fructose intolerance
## Footnote
* (less specific: vomiting, lethargy, liver dysfunction)*
* Enzyme: Fructose-1-phosphate aldolase*
97
Name the IEM known for: cardiomegaly/CHF
Pompe, i.e. glycogen storage disease type II
## Footnote
* Hypoglycemia, severe weakness*
* Enzyme: lysosomal alpha-glucosidase (enzyme name's misleading, it's a GSD!)*
98
Name the IEM known for: hyperammonemia, LOW orotic acid (urine)
Carbamyl phosphate synthetase deficiency
(Technically N-acetylglutamate synthetase too but doesn't seem tested as much)
*Urea cycle defect*
99
Name the IEM known for: hyperammonemia, HIGH orotic acid (urine), LOW citrulline
Ornithine transcarbamylase deficiency
*Urea cycle defect*, ***X-linked***
100
Name the IEM(s) known for: hyperammonemia, HIGH orotic acid (urine), HIGH citrulline
Argininosuccinic ...\_\_\_\_ (i.e. argininosuccinic acid synthetase deficiency and argininosuccinic lyase deficiency)
## Footnote
*Arginino**_S_**u_CC_inic urea cycle defects have high **_CIT_**rillune*
101
Name the IEM known for: sweet urine
Maple syrup urine disease
## Footnote
* Lethargy, ALTERNATING hypo/hyper-tonia, seizures*
* Enzyme: branched alpha-ketoacid dehydrogenase*
102
Name the IEM known for: mousy urine
Phenylketonuria
## Footnote
*Enzyme: Phenylalanine hydroxylase (classic)*
103
Name the IEM known for: downward dislocated lenses
Homocystinuria (aminoacidopathy)
## Footnote
* Tall stature (only one, most are FTT), arachnodactyly, seizures, thromboses (vascular disease)*
* Enzyme: Cystathione synthetase (most commonly)*
104
Name the IEM**s** known for: absent corpus callosum
**_Hy_**perglycinemia (**_HI_**ccups when you're **_HI_**gh up [in utero])
Mitochondrial disorders: Pyruvate carboxylase and pyruvate dehydrogenase
105
Name the IEM known for: Fanconi syndrome (i.e. Type II RTA)
Tyrosinemia (aminoacidopathy)
## Footnote
* FTT, hepatomegaly, liver dysfunction, **albinism***
* Enzyme: **_F_**umarylacetoacetate hydrolase causes **_F_**anconi renal problems*
106
Name the IEM known for: sweaty feet ODOR
Isovaleric acidemia (organic acidemia)
* If present in neonatal period, have 50% chance of death*
* Enzyme: Isovaleryl-CoA dehydrogenase*
107
Diagnosis: camptodactyly, cupped ears, cognitive impairment
Trisomy 8
## Footnote
***_C_**upped ears and **_c_**urved fingers*
108
Diagnosis: cleft lip/palate, cutis aplasia, VSD, narrow hyperconvex fingernails, hypsarrythmia/seizures
Trisomy 13
## Footnote
*Higher mortality than Trisomy 18*
109
Diagnosis: small factial features, clinodactyly (overlapping fingers), rocker bottom feet, VSD or coarctation
Trisomy 18
## Footnote
*On quad screen will have low AFP, bHCG, and estradiol*
110
Diagnosis: upslanting palpebral fissures, clinodactyly, VSD (or other endocardial cushion defect), hypotonia
Trisomy 21
*Increased risk: duodenal atresia, Hirschsprung's, hypothyroidism, transient myeloproliferative disorder (TMD/TMPD), AML (or any leukemia)*
111
Diagnosis: downslanting palpebral fissures, transverse palmar crease, VSD, hypotonia, cat-like cry
Cri du chat
## Footnote
*Chromosome 5**_p_** deletion, usually **_p_**aternal origin*
112
Diagnosis: large mouth, seizures, jerky movements
Angelman syndrome\*
* 15q11-13 deletion of MATERNAL copy (either by microdeletion but inherit maternal chr15, or by paternal uniparental disomy)*
* \*Rare for genetic d/o to have no cardiac assocations, but it doesn't!*
113
Diagnosis: short digits, hypotonia, cryptorchidism, poor PO, breech presentation
**_P_**rader-Willi\*
* 15q11-13 deletion of **_P_**ATERNAL copy (either inherit paternal chr15 but microdeletion, or get maternal uniparental disomy)*
* \*Rare for genetic d/o's to not have cardiac anomalies, but does not!*
114
What branchial arch does not develop properly in 22q11, i.e. CATH 22?
Fourth arch (third/fourth pharyngeal pouches which is where thymic hypoplasia comes from)
## Footnote
*ARCH has 4 letters and it's the one that's messed up with aortic ARCH problems*
115
Diagnosis: beaked nose, maxillary hypoplasia, downslanting palpebral fissures, PDA, broad thumbs
Rubinstein-Taybi
## Footnote
* VSD or ASD seem equally common (25-35% have some cardiac defect); speech difficulties, increased malignancies*
* 16p13.3 deletion of CREB (cAMP-regulated enhancer binding)*
116
Diagnosis: aniridia, cryptorchidism, cognitive impairment, Wilm's
WAGR (Wilm's, aniridia, GU abnormalities [less apparent in females], retardation)\*
## Footnote
* 11p13 deletion (other syndrome from chr11 deletion is Beckwith-Wiedemann)*
* \*No cardiac malformations associated*
117
Diagnosis: elfin-like facies (thin upper lip), supravalvar aortic stenosis, hypocalcemia
William's syndrome
* Hypocalcemia's transient; pulmonic stenosis/peripheral pulmonic stenosis are also common*
* 7q11.23 deletion, elastin gene (**_E_**lfin facies from **_e_**lastin gene)*
(https://www.physio-pedia.com/William%27s_Syndrome)
118
119
What to supplement with in: FAOD (fatty acid oxidation defects)
Carnitine True for MCHAD (most common FAOD) and carnitine deficiency (but definitely won’t hurt anything in LCHAD)
120
How to manage: Maple Syrup Urine Disease (MSUD)
Restrict branched AA (isoleucine, leucine, valine) Supplement with thiamine (B1 for BRANCHED enzyme defect)
121
How to manage: Phenylketonuria
Restrict phenylalanine (essential AA so can’t cut out!) May need tetrahydropterin (BH4) supplementation
122
How to manage: Tyrosinemia
Restrict phenylalanine, tyrosine, methionine (most are essential AA) Nitisinone (decreases toxic metabolites)
123
What is nitisinone for?
Tyrosinemia Inhibits phenylpyruvate metabolism so decreases toxic metabolites (e.g. fumarylacetate)
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What is the diagnosis: Elevated succinylacetate (serum and urine)
Tyrosinemia Will also see elevated serum tyrosine and methionine with NORMAL phenylalanine
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What is the diagnosis: Elevated methionine, excess homocysteine
Homocystinuria
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How to manage: Homocystinuria
High pyridoxine Decrease methionine (remember it’s an essential AA!) Supplement cysteine and folate
