Biochem Flashcards
(319 cards)
1
Q
Lactic acidosis
A
Galactosemias
2
Q
Avoid legumes
A
GALT/Gal-1-P Deficiency
3
Q
Only symptom is cataracts
A
GALK Deficiency
4
Q
Dietary lactose and galactose restriction
A
GALE Deficiency
5
Q
Galactosemias
A
GALT/Gal-1-P Deficiency
GALK deficiency
GALE deficiency
6
Q
Liver dysfunction Renal dysfunction Hypoglycemia Cataracts Dairy intolerance Lactic acidosis Hyperuricemia
A
General features of Galactosemias
7
Q
Glycogen storage diseases
A
Von-Gierke Disease
Pompe Disease
McArdle Disease
8
Q
Cornstarch between meals
Nighttime glucose infusions
A
Von-Gierke disease (GSD type 1)
9
Q
Cardiomegaly, hypotonia, cardiomyopathy, respiratory distress, recurrent respiratory infections, enlarged tongue
A
Pompe - infantile type
10
Q
Sucrose supplementation before exercise
Vitamin B6 supplementation
High protein/fat diet
A
McArdle Disease (GSD V)
11
Q
Myoglobinuria, myopathy, skeletal muscle weakness, exercise intolerance, rhabdomyolysis
A
McArdle disease (GSD V)
12
Q
Hypoglycemia, hyperlipidemia, Hyperuricemia, lactic acidosis, liver dysfunction/hepatomegaly, DD, seizures, GI problems, growth retardation, renal problems/kidney stones
A
Von gierke (GSD 1)
13
Q
X-Linked LSDs
A
Fabry
Danon disease
Hunter syndrome (MPS II)
14
Q
Neurodegeneration Vision problems Seizures Personality and behavioral changes Echolalia Clumsiness Poor growth Poor circulation to lower extremities Decreased body mass Breath holding spells Bruxism Neuro degeneration leading to death between 6 yrs and teenage years
A
Batten disease (LSD)
15
Q
Hypertrophic cardiomyopathy Wolff Parkinson White conduction abnormality Skeletal muscle myopathy Visual/retinal pigment disturbances ID (usually absent in females)
A
Danon disease (LSD - X-linked dominant) gene - LAMP2
16
Q
Pain and tingling in limbs, pain crises, angiokeratomas, anhidrosis/hypohidrosis, corneal whorl, left ventricular hypertophy, GI problems, renal insufficiency (protein urea), depression secondary to chronic pain
A
Fabry disease (X-linked)
17
Q
Corneal whorls
A
Fabry
18
Q
Erlenmeyer flask deformity
A
Gaucher disease
19
Q
Splenomegaly, thrombocytopenia, pulmonary hypertension, bone crises, Erlenmeyer flask deformity, no cns involvement
A
Gaucher type 1
20
Q
Bulbar and pyramidal signs, ID, convulsions, hypertonic, apnea, no bone disease/crises, hepatosplenomegaly, thrombocytopenia, pulmonary hypertension, dermatological abnormalities
A
Gaucher type 2 (most severe)
Lifespan: 2-4 years
21
Q
Progressive myoclonus epilepsy, oculomotor apraxia, hepatosplenomegaly, thrombocytopenia,
Pulmonary hypertension, bone crises, Erlenmeyer flask deformities, chronic neuropathies
A
Gaucher type 3
22
Q
What type of gaucher is ERT not effective for?
A
Type 2
23
Q
Irritability, fevers, stiffening of limbs, seizures, feeding difficulties/vomiting, mental and motor delay, muscle weakness, spasticity, deafness, optic atrophy and blindness, paralysis
A
Krabbe - death by age 2 :(
24
Q
DD, ID, regression, hepatosplenomegaly, skeletal anomalies, short stature, cardiac anomalies, corneal clouding, hearing loss
A
Hurler-scheie (MPS I)
25
DD, ID, regression, skeletal anomalies, short stature, cardiac anomalies, clear corneas, hearing loss
Hunter syndrome (MPS II - X-linked)
26
Milder skeletal phenotype, coarse facies, progressive sleep and behavior problems, no cardiac anomalies, clear corneas
San-Filippo Syndrome (MPS III)
27
Severe skeletal phenotype (short trunked dwarfism), normal intellect, chest deformities, cardiac anomalies, bone malformation, macrocephaly
Mosquito syndrome (MPS IV)
28
Skeletal anomalies, short stature, cardiac anomalies, corneal clouding, normal intellect
Maroteaux-Lamy (MPS VI)
29
DD, regression, cardiac anomalies, hepatosplenomegaly, recurrent ENT problems
Sly syndrome (MPS VII)
30
Mildest type of Niemann Pick
Type B
31
```
Hepatosplenomegaly
Failure to thrive
Progressive nervous system deterioration
Profound brain damage
Development stops at 1 year and regresses
Pulmonary insufficiency
Recurrent lung infections
Cherry red spot
Death by 3 years
```
Niemann pick type A
32
Form of Niemann Pick where cognitive function may be spared
Type B
33
```
Hepatosplenomegaly
Dystonia
Dysphasia
Progressive neurological deterioration
Cerebellum ataxia
Dysarthria
Vertical supranuclear gaze palsy
Psychosis
Progressive HL
```
Niemann pick type C
34
Hyperammonemia
Urea cycle disorders
35
Severe acidosis
Organic acidemias
36
Lethargy and seizures
MSUD
37
Jaundice, hypoglycemia, liver failure
Galactosemias
38
Hypoglycemia, weakness, cardiac
FAOD
39
Hypoglycemia, circulatory collapse
CAH
40
Transient Hyperammonemia is associated with _
Asphyxia (low APGARs)
41
Rapid and shallow breathing
Hyperammonemia
42
Deep breathing
Acidosis
43
Propionic, methylmalonic, isovaleric
Organic acidemias
44
Primary lactic acidosis
Mito (ETC) defects
| Pyruvate dehydrogenase deficiency
45
Hyperpnea - rapid breathing
Urea cycle defects
46
Kussmaul - deep breathing
Organic acidemias
47
Respiratory depression
MSUD
48
Hiccuping and apnea
Nonketotic hyperglycinemia
49
Hypoglycemia in newborns differential
```
Normal
CAH
FAOD
Galactosemias
Propionic acidemia
Gluconeogenic defects
```
50
Hepatomegaly in newborn
Galactosemias
Tyrosinemia (usually later)
FAOD
LSD (usually later)
51
Seizures in newborn
```
Nonketotic hyperglycinemia
Urea cycle defects (Hyperammonemia)
Organic acidemias (Hyperammonemia, hypoglycemia)
Gluconeogenic defects (hypoglycemia)
LSDs (usually later)
```
52
Amino acids disorders
Urea cycle, organic acidemias, MSUD, nonketotic hyperglycinemia
53
Carbohydrate disorders
Galactosemias, gluconeogenic defects, electron transport chain defects
54
Female heterozygote may be protein intolerant
OTC
55
Vomiting, hyperpnea, lethargy
Organic acidemias
56
Vitamin B12 enzyme
Methylmalonic acidemia
57
Elevated C3 acylcarnitine
Methylmalonic acidemia
58
Sweaty feet
Isovaleric acidemia
59
Riboflavin (vitamin B2)
Isovaleric acidemia
60
Elevated C5 acylcarnitine
Isovaleric acidemia
61
Branched chain ketoacid dehydrogenase
MSUD
62
Elevated leucine in NBS
MSUD
63
Lethargy, hypotonia, respiratory depression, seizures.
| Progresses to vomiting, ketoacidosis
MSUD
64
Liver failure, E. Coli sepsis
Galactosemia
65
Jaundice, hepatomegaly, vomiting
Galactosemia
66
Improve on IV fluids and then get worse when fed
Galactosemia
67
Fasting hypoglycemia, liver disease, myopathy
FAOD
68
C8 acylcarnitine
MCAD
69
C14:1 acylcarnitine
VLCAD
70
Long chain defects can cause
Progressive liver/muscle disease
71
Prenatal virilization in females
CAH and antley bixler
72
Salt wasting
21-OH deficiency
73
Defects in what also cause elevated phenylalanine?
tetrahydrobiopterin (BH4 needed in other reactions and does not respond to PKU diet alone)
74
Teratogen that causes microcephaly and heart malformations
Maternal PKU
75
What does Galactose-I-phosphate do?
Converts galactose (in milk) to glucose (blood sugar)
76
Feeding intolerant, vomiting, liver failure (jaundice liver enlargement, blood clotting abnormalities), predisposition to infections
Galactosemia
77
Resolves when milk is removed from the diet
Galactosemia
78
Duarte variant
N314D - common variant sometimes picked up by galactosemia screening (low activity, 5% population frequency, does not require treatment)
79
False positives in summer
NBS that tests for enzyme levels of galactosemias (GalPUT, GALT)
80
Hypoglycemia, coma, "SIDS"
MCAD
81
A985G
Common MCAD mutation (>90% of Caucasian MCAD mutations)
82
Hexanoylglycine
MCAD - Acylglycine analysis
83
Most frequent condition in NBS
Hypothyroidism (1/3000)
84
Lethargy, sleepiness, poor feeding and growth, hoarse cry, DD
Hypothyroidism (treated with oral thyroid hormone replacement)
85
Start T4 replacement as soon as possible
Hypothyroidism NBS
86
Poor feeding, lethargy, virilization of females, salt wasting
Congenital Adrenal Hyperplasia (CAH)
87
Cortisol and Florinef (mineralocorticoid) + NaCl = treatment
CAH
88
Methionine increased on PAA
homocystinuria
89
Citrulline increased on PAA
Urea cycle disorders
90
Leucine increased on PAA
MSUD
91
Fasting or feeding specimens for PAA?
Fasting preferred
92
C3 on Acylcarnitine
Propionylcarnitine (propionic or methylmalonic acidemia)
93
B12 defects
Methylmalonic aciduria and homocystinuria
94
Skeletal dysplasia, joint stiffness, organomegaly, intellectual deterioration, excretion of "glycosaminoglycans" in urine
General features of MPS
95
Glycosaminoglycans
Mucopolysaccharides (other name)
96
Acute acidosis in neonatal period
Methylmalonyl-CoA mutase deficiency or Propionic acidemia
97
Defect in methionine metabolism
Homocystinuria
98
Folate defect
Homocystinuria - associated with thrombosis and neural tube defects
99
Multiple carboxylase deficiency
Biotin defects
100
_ granules in liver cells
Glycogen
101
_ cells in bone marrow
"Gaucher"
102
Categories of Lysosomal Storage Diseases
Glycolipidoses, Mucopolysaccharidoses, Oligosaccharidoses
103
Glycolipidoses
Gangliosides, cerebrosides, etc.
| Gaucher, Niemann-Pick, Tay-Sachs, Krabbe, Fabry, etc.
104
MPS
Glycosaminoglycans
105
Oligosaccharidoses
Glycoproteins
| Similar to MPS
106
Sphingolipids
Think LSDs
107
Glycogen accumulation in tissues
Liver, Heart, Skeletal muscle (Glycogen Storage Diseases)
108
Fasting hypoglycemia
Glycogen Storage Diseases
109
Muscle weakness, pain on exercise
Glycogen Storage Diseases
110
Enlarged spleen, anemia, low platelet count (thrombocytopenia), Interstitial lung disease, Bony involvement (pathologic fractures)
Gaucher Disease - "Erlenmeyer Flask" on X-ray
111
Low platelet count
thrombocytopenia
112
N370S
Common AJ mutation in Gaucher type I
113
L444P
Common Swedish mutation in Type 3 Gaucher
114
Neuronopathic type of Gaucher
Type 3, slowly progressive neurologic disease
Distubance of upward gaze
Common mutation in Swedish population
115
Sphingomyelinase deficiency
Causes Types A and B of Niemann Pick
116
Cholesterol trafficking defect
Niemann-Pick type C
117
Hepatosplenomegaly, hypotonia, neurologic deterioration, poor growth
Niemann-Pick Disease
118
Palsy of upward gaze
Type C Niemann-Pick
119
Dysostosis multiplex on X-ray
MPS (and other LSD's)
120
Hepatosplenomegaly, corneal clouding, bony involvement - dysostosis multiplex, +/- progressive neurologic impairment, obstructive/restrictive pulmonary disease, cardiac valve dysfunction, hearing loss
MPS in general
121
Defects in glycogen breakdown lead to
fasting hypoglycemia
122
"fast twitch" muscles use
glucose as preferred energy source
123
Defects in glycogen breakdown lead to energy deficit
Weakness, pain, cramping, muscle breakdown after exercise
124
Hepatosplenomegaly, FTT, progressive cirrhosis, liver failure, myopathy/cardiomyopathy
GSD IV
125
Spectrum of severity for GSDs
GSD1 is most severe, GSD VI is least severe
126
Leukodystrophy
Brain white matter changes on MRI
127
CK or CPK
Muscle enzyme, elevation indication of muscle breakdown
128
Infantile presentation: loss of skills, seizures, swallowing difficulties, no organomegaly (Loss of ALL skills at 12 months, unresponsive and seizures)
Tay-Sachs
129
Cause of death in Tay-Sachs
Respiratory deficiency by 2 - 4 years
130
Infantile onset (weakness, stiffness, scissoring of legs, opisthotonic posturing (head back, back arched), irritability, excessive startle to loud noise, no organomegaly, normal eye findings
Krabbe disease
131
galactocerebrosidase deficiency
Krabbe
132
Treatment by hemapoietic stem cell transplant
(bone marrow transplant) - Krabbe disease
133
Weakness, floppiness, heart enlargement (cardiomegaly), CK elevated, Abnormal EKG (short PR interval), no hypoglycemia or liver enlargement, progressive heart and respiratory failure
Pompe disease (infantile - death in first year)
134
High carb diet may help
Muscle GSDs
135
Weaknes, cardiomeagly, fasting intolerance, lipid myopathy, abnormalities on acylcarnitine profile
VLCAD or other long chain FAOD
136
Supplementation with medium chain triglycerides may help
VLCAD
137
Hepatomegaly, myopathy, lactic acidemia, Short Fasting period (<6 hours)
Glycogen Storage Disorders
138
Lethargy, vomiting, transient hepatomegaly/liver failure, may have cardiomyopathy, no lactic acidosis, sudden death
FAOD
139
Produces ATP, not glucose directly
Fatty acid oxidation
140
_ do not require carnitine for oxidation
Medium chain fatty acids
141
Produce glucose from carbon skeletons of amino acids, lactic acidemia, +/- hepatomegaly, normal organic acids
Disorders of gluconeogenesis
142
Permanent hepatomegaly, uncommon muscle weakness, severe hypoglycemia after short fast, lactic acidema (may be severe), hyperlipidemia, hyperuricemia
Von Gierke's disease (GSD Type I)
143
Management: frequent feedings, cornstarch q6h, nighttime NG or G-tube drip feeds
GSD type I (von Gierke's)
144
Hepatomegaly, +/- myopathy (cardiac involvement in some), severe hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, liver symptoms may resolve by adulthood, progressive hypertrophic cardiomyopathy
GSD Type III (Cori or Forbes disease)
145
Inheritance pattern of phosphorylase kinase
X-Linked (GSD)
146
Hepatomegaly, fasting hypoglycemia, mild lactic acidemia, mild hyperlipidemia
Types VI and up of GSD's (Hers disease, unnamed)
147
Dicarboxylic aciduria with acyl-glycines on UOA
FAOD
148
Hydroxydicarboxylic aciduria on UOA
FAOD
149
What do you order for a suspected FAOD?
UOA, carnitine level, acyl-carnitine profile
150
Female heterozygotes at higher risk for HELLP (Hypertension, Elevated Liver enzymes, Low Platelets) during pregnancy - acute fatty liver of pregnancy
LCHAD
151
Trifunctional enzyme deficiency, Hypoketotic hypoglycemia, cardiomyopathy, some with retinopathy
LCHAD
152
Disorders of gluconeogenesis
Pyruvate Carboxylase Deficiency
Fructose-1,6-bisphosphatase deficiency
153
Fasting hypoglycemia associated with lactic acidemia, +/- hepatomegaly, organic acids normal (except lactate)
Disorders of gluconeogenesis
154
Hypoglycemia, lethargy after more prolonged fasting, poor response to metabolic stress, salt wasting (low blood sodium)
CAH
155
_ increases positive predictive value
Disease frequency
156
Recommended Core Panel for NBS
34 conditions: 9 organic acidemias, 5 FAOD, 6 amino acidopathies, 2 endocrine, 3 hemoglobinopathies, 9 others
157
Elevated 17-OHP
CAH testing
158
Arginine supplementation
Urea cycle defects
159
Citrulline supplementation
CPS or OTC
160
Thiamin supplementation
MSUD
161
Tetrahydrobiopterin supplementation
PKU
162
B6 supplementation
Homocystinuria
163
B12 supplementation
Methylmalonic aciduria
164
Liver transplant helpful in
Urea cycle defects, Tyrosinemia (liver failure), Methylmalonic acidemia (WITH a kidney transplant)
165
Hematopoietic stem cells (bone marrow) helpful in
LSD's (specifically MPS and Krabbe), Hemoglobinopathies
166
ERT helpful in
LSDs
167
Cabbage smell
Tyrosinemia
168
Onset between 4 - 8 years of age, progressive neurodegenerative decline, behavioral and learning deficits, seizures, adrenocortical dysfunction, total disability and early death 6 months to 2 years after onset
X-linked Adrenoleukodystrophy: childhood cerebral form
169
Progressive stiffness and weakness in the legs, abnormal sphincter control, sexual dysfunction, adrenocortical dysfunction, neuropathy, 40-50% with leukodystrophy, onset in 20s
Adrenomyeloneuropathy (form of X-linked Adrenoleukodystrophy)
170
Adrenal insufficiency in the absence of MRI/brain anomalies, increased skin pigmentation from excess ACTH
Addison's disease (isolated)
171
Corticosteroid replacement therapy
X-linked Adrenoleukodystrophy
172
Alpha-glucosidase deficient
Pompe Disease
173
Myophosphorylase deficient
McArdle Disease
174
Galactosylceramidase deficient
Krabbe Disease
175
Slowly progressive neurodegeneration, progressive muscle wasting, dysarthria, fasciculations, cognitive dysfunction, dementia, psychiatric problems, psychosis, can be indistinguishable from progressive adolescent-onset SMA or ALS
Adult-Onset Tay Sachs
176
Sweaty Feet
Isovaleric Acidemia (can also be glutaric acidemia)
177
Metabolic acidosis, protein aversion, thrombocytopenia, vomiting, poor feeding, coma, seizures, DD, 50% severe acute neonatal with rapid death, 50% chronic and episodic with asymptomatic intervals
Isovaleric Acidemia (Biotin deficiency can mimic this)
178
Dietary leucine restriction and glycine supplementation during acute episodes
Isovaleric Acidemia
179
ID, DD, growth retardation, opisthotonic posturing, dysphagia, self-injuring behavior, hyperuricemia, renal failure
Lesch-Nyhan Syndrome (X-LINKED)
180
Affected females typically only present with hyperuricemia
Lesch-Nyhan
181
Respiratory alkalosis, hyperammonemia, vomiting, lethargy, seizures, coma, untreated = ID/DD
General symptoms of Urea cycle disorders
182
Proximal Urea cycle disorders
CSP1, NAGS, OTC (NO A's)
183
Distal Urea Cycle Disorders
ASS, ASL, ARG (ALL A's)
184
Absent or low citrulline (plasma concentration)
Proximal disorders of urea cycle (CSP1, NAGS, OTC)
185
Elevated Citrulline (plasma concentration)
Distal urea cycle disorders (ASS, ASL, ARG)
186
Dietary protein restriction
Urea cycle disorders
187
Medications that provide alternate pathways for ammonia removal
Urea cycle disorders
188
Nitrogen scavenger therapy
Proximal Urea cycle disorders (CSP1, NAGS, OTC)
189
Function within the mitochondria
Proximal Urea Cycle Disorders (CSP1, NAGS, OTC)
190
Elevated ammonia levels, severe lethal neonatal onset or less severe later onset later
CPS1 (Carbamoyl phosphate synthetase 1)
191
Elevated ammonia levels, N-acetylglutamate synthetase
NAGS
192
Most common urea cycle disorder
OTC
193
Elevated ornithine, uracil, and orotic acid. May present neonatally or in childhood after illness or high protein intake
OTC
194
Elevated citrulline
ASS (Arginosuccinic acid synthetase)
195
Elevated citrulline and argininosuccinic acid
ASL (arginosuccinic acid lyase)
196
Elevated arginine, hyperammonemia is rarely present, slower onset and muscle weakness is often present
ARG (Arginase)
197
COPD with otherwise unknown etiology, liver disease at any age, C-ANCA Positive vasculitis, necrotizing panniculitis (inflammation of the fatty fibrous tissue directly beneath the skin)
Alpha-1-Antitrypsin Deficiency
198
Classic triad of hypotonia, head lag, and macrocephaly
Canavan disease
199
Leukodystrophy, hypo or hypertonia, ID, motor skill regression, feeding difficulties, poor head control, macrocephaly, paralysis, blindness, seizures, shortened lifespan (teens)
Canavan disease
200
Most common human enzymatic disorder
Glucose-6-phospate Dehydrogenase Deficiency (G6PD)
201
Inheritance of G6PD
X-linked
202
Prolonged neonatal jaundice (can lead to kernicterus if untreated), hemolytic crisis (rupturing of RBC's) in response to triggers (illness, antimalarial drugs, analgesics, sulfonamides, certain foods (FAVA BEANS), certain chemicalse), diabetic ketoacidosis, a severe crisis can lead to kidney failure, presentation is USUALLY mild
G6PD
203
G6PD may confer some protection against
Malaria
204
Avoid Fava beans
G6PD
205
Common in African, MIddle-Eastern, and Southeast Asian descent
G6PD
206
Elevated serum ferritin
Hemochromatosis
207
Hepatomegaly, cirrhosis, hepatocellular carcinoma, diabetes, cardiomyopathy, hypogonadis, arthritis, progressive increase in skin pigmentation
Hemochromatosis
208
Treatment:
| Low iron diet, therapeutic phelebotamy, liver transplant may be required if substantial damage
Hemochromatosis
209
Elevated serum 7DHC
Smith Lemli Optiz
210
moderate to severe ID, microcephaly, behavior (aggression, self-injury, autism), sensory hypersensitivity, strabismus, cataracts, CHD, Gi issues, pyloric stenosis, feeding difficulties, renal anomalies
SLO
211
2,3-syndactyly of toes
SLO
212
Postaxial polydactyly of hands/feet, ambiguous genitalia, hypospadias, bitemporal narrowing, short and upturned nose, ptosis, micrognathia, epicanthal folds, capillary hemangioma of the nose
SLO
213
Kayser-Fleischer rings
Wilson Disease (copper rings on irises)
214
Liver disease (recurrent jaundice, hepatitis, fatty liver, hemolytic anemia), neurologic disease (tremors, poor coordination, loss of fine motor control, chorea, spastic dystonia), Psychiatric manifestations (depression, aggression, phobias, antisocial behavior, poor memory, shortened attention span)
Wilson disease
215
Minor features: renal problems, arthritis, pancreatitis, cardiomyopathy, sunflower cataracts
Wilson disease
216
Leukodystrophies
Krabbe, Metachromatic leukodystrophy, X-Linked Adrenoleukodystrophy, Canavan disease, Mito disease. ALL ARE PROGRESSIVE AND NEURODEGENERATIVE.
217
Globoid cell leukodystrophy
Early irritability (Krabbe)
218
Metachromatic Leukodystrophy
Vision loss
219
X-linked leukodystrophy
Behavioral changes
220
Leukodystrophy with macrocephaly
Canavan disease
221
Fasting intolerance, liver enlargement/dysfunction, recurrent vomiting/lethargy/coma, cardiomyopathy
FAOD
222
Hypoketotic hypoglycemia, low carnitine, abnormal organic acids, abnormal acylcarnitines and acylglycines, +/- hyperammonemia, +/- hyperuricemia
FAOD
223
Adult onset cases may present with muscle cramping and myoglobinuria
FAOD
224
Low ketone production
MCAD, LCHAD, VLCAD, and carnitine transport disorders
225
Significant ketosis
SCAD
226
Most common cause of CAH
21-OH deficiency, increased 17-OH progesterone which causes increased androgens - salt wasting and virilization of pregnant moms
227
At risk areas of brain scans in metabolic disease
Basal ganglia (stroke-like episodes), White matter, Infarction (stroke like episodes)
228
Basal ganglia (stroke like episodes) metabolic disorders
organic acidemias (glutaric acidemia type I, propionic and methylmalonic acidema)
229
White matter changes
Leukodystrophies
230
Can see _ on brain MRI from hyperammonemia
Infarction
231
Glutacylcarnitine suggests a possible diagnosis of
Glutaric acidemia types I or II
232
Acylcarnitine specimens obtained when the patient is _ may be the most informative, although specimens when the patient is _ may also be diagnostic
Sick, healthy
233
Aclyglycines are ordered to
diagnose FAOD and organic acidemias
234
Phenylketones are or are not usually seen in healthy people
ARE NOT (indicates problems with PAH)
235
Archibald Garrod
Father of Biochem Geneics. Seminal paper written on alkaptonuria in 1902. Coined "IE of M"
236
IE of M symptoms are due to
small molecules accumulation of substrates or deficiency of products; generally recessive (consequence of kinetic properties of enzymes)
237
A liver transplant may be effective in treating
Severe FH, Alpha-1 Antitrypsin deficiency, OTC deficiency
238
crm + or - (which one is more difficult to treat)
crm-
239
crm
cross reacting material. reflect amount of protein, not how active the enzyme is
240
fibroblast studies require a
skin biopsy and culture
241
Acylcarnitine profile
Blood is preferred. Tandem mass spec. Acylcarnitines reflect intracellular acyl-CoA's. CoA species themselves are only intracellular.
242
Urea cycle disorders
CPS, Citrullinemia, NAGS, Argininosuccinic aciduria, Arginase deficiency, OTC deficiency
243
Organic acids
Uses GC/MS. Usually urine. Methylmalonic acid, propionic acid, isovaleric acid, branched chain ketones in MSUD. Generally derivatives of AA's.
244
Irritable, refused to feed DOL4, lethargy, pale, hypotonic, poorly responsive, primary respiratory alkalosis, very high ammonia, apneic requiring intubation an dventilation, generalized seizure, hemodialysis, IV = sodium benzoate, sodium phenylacetate, and L-arginine
OTC presentation
245
Primary respiratory alkalosis
OTC
246
Urinalysis
Can identify renal tubular disease (e.g. in tyrosinemia I, galactosemia, mito disease). The kidney has trouble absorbing glucose, bicarbonate, and other analytes.
247
Oozing from phlebotomy sites
Tyrosinemia type I
248
Rickets
Tyrosinemia type I
249
Increased ph and glucose on urinalysis
Tyrosinemia type I
250
Urine ketones
Helpful in detecting and monitoring organic acidemias or in distinguishing ketotic (normal) from hypoketotic hypoglycemia (abnormal in fatty acid oxidation defects and glycogen storage disease I)
251
Urine reducing substances
If positive, indicates a reducing substance (e.g. glucose, galactose, fructose). Glucose is most common reducing substance.
252
Worry if the diagnostic urine specimen is _ but _. Could mean galactosemia or fructose intolerance.
Negative for glucose, but positive for reducing substances.
253
Acute metabolic liver disease
Tyrosinemia type I and galactosemia (liver: liver failure, cirrhosis, ascites, coagulopathy, fasting intolerance)
254
Acute fatty liver
- "Reye syndrome-like disease"
- FAOD.
- Urea cycle defects.
255
GAA gene
Pompe
256
DD, LD, Insensitivity to pain; self-injurious behavior, renal stones (uric acid), hyperuricemia
Lesch-Nyhan (X-linked)
257
Gram negative sepsis
Galactosemia
258
Neutropenia
Propionic acidemia, methylmalonic acidemia, GSD type 1B
259
Pancytopenia
Pearson syndrome (mito)
260
Neutropenia and splenomegaly
Gaucher
261
Otitis media, respiratory infections, splenomegaly
LSDs
262
Metabolic acidosis
When HCO3 is low
263
Secondary respiratory alkalosis
Organic acidemias, when both pH and pCO2 is low
264
The body does not store amino acids or protein. Whatever is not used is _
degraded, producing waste nitrogen (ammonia).
265
Arginase deficiency
- Urea cycle defect
- usually presents with chronic neurologic presentation (e.g. DD and spastic diplegia)
- Acute hyperammonemic crises are uncommon
266
- Often associated with chronic liver enlargement/dysfunction
- May be associated wtih trichorrhexis nodosa (kinky hair)
Argininosuccinic Aciduria
267
Kinky hair
Menkes (X-linked recessive, affects copper levels) or Argininosuccinic aciduria (urea cycle disorder)
268
Macrocephaly, unusual fluid collections (pre-frontal and temporal lobes), "metabolic stroke-like features" causing severe dystonia and motor impairment.
Glutaric acidemia type I
269
Motor delays, seizures, hyperactivity, inattentiveness, ID, dry and scaly skin, psych disturbances, hypopigmentation, eczema
PKU
270
What is salt wasting?
Low sodium, high potassium due to aldosterone deficiency
271
Metabolic disorders that present prenatally
- Zellweger syndrome
- Glutaric acidemia type II
- Pyruvate dehydrogenase complex deficiency
- Carbohydrate-deficient glycoprotein syndromes
- Smith-Lemli-Opitz syndrome
272
MPS with hydrops fetalis
Sly syndrome
273
MPS with most severe skeletal disease, normal intelligence
Morquio
274
MPS with mildest somatic symptoms, frequently have behavioral problems with progression to severe neruologic disease
Sanfilippo
275
Normal intelligence MPS
Morquio and Maroteaux-Lamy
276
Earliest onset and most severe MPS
Hurler syndrome
277
MPS with X-linked inheritance
Hunter syndrome
278
Alpha-L-iduronidase
MPS 1 (Hurler)
279
Iduronate 2-sulfatase
MPS 2 (Hunter)
280
Arylsulfatase B
MPS VI (Maroteaux-Lamy)
281
Beta-glucuronidase
MPS VII (Sly)
282
Increased Keratan Sulfate (Glycosaminoglycans - GAGs)
MPS IV (Morquio)
283
Increased Dermatan Sulfate and Heparan Sulfate (Glycosaminoglycans - GAGs)
MPS I, MPS II, MPS VII
284
Increased Heparin Sulfate
MPS III
285
Increased Dermatan Sulfate
MPS VI
286
Increased pH, decreased pCO2 and HCO3
Urea cycle disorders - primary respiratory alkalosis and secondary metabolic acidosis
287
Primary respiratory alkalosis and secondary metabolic acidosis
Urea cycle disorders (increased pH, decreased pCO2 and HCO3)
288
In urea cycle disorders, _ acts as a central respiratory stimulant causing _
NH3 (ammonia), causing hyperventilation and a decreased in CO2.
289
How to distinguish CPS from OTC
orotic acid is significantly elevated in OTC and low to low-normal in CPS
290
Urea cycle defects that do NOT exhibit high orotic acid excretion in the urine
NAGS and CPS deficiencies (OTC has significantly elevated)
291
Clinical phenotype of OTC deficiency in females
Can be symptomatic later in life in times of metabolic stress. This can happen as a result of anorexia, starvation, malnutrition, pregnancy or even as a result of gastric bypass surgery. Approximately 15% of females develop hyperammonemia during their lifetime and may require chronic medical managemetn for hyperammonemia.
292
Primary metabolic acidosis and secondary respiratory alkalosis
Organic acidemias - TOO MUCH ACID, the body does not want to be acidotic so rapid breathing and excess releas of CO2 generates a respiratory alkalosis.
293
Low pH, pCO2, HCO3
Primary metabolic acidosis and secondary respiratory alkalosis (TOO MUCH ACID) - organic acidemias
294
Increased incidence in Mennonite population
MSUD
295
Urea cycle disorders - Plasma arginine levels
Low in everything EXCEPT Arginase deficiency, in which it is increased 5 - 7 fold.
296
Dietary therapies in metabolic disorders
Substrate restriction, altering feeding regimens, supplementation of the dietary product
297
Chelating agents as therapy
Wilson disease
298
Citrulline levels in Urea cycle defects
Decreased in NAGS, CPS, and OTC; increased in Citrullinemia type I, Argininosuccinic aciduria, and Arginase deficiency
299
Citrulline is a product of _ and _ but a substrate for _
CPS I and OTC but a substrate for the distal enzymes
300
Fair complexion in PKU is due to
tryosine deficiency
301
"doll-like facies"
von Gierke disease
302
Aversion to sweets over time
Hereditary fructose intolerance
303
ASS is also known as
Citrullinemia
304
Prenatal onset, dysmorphic, hypotonia, seizures, liver disease, death within months
Zellweger disease (leukodystrophies - peroxisomal disorder)
305
Neurologic phenotypes
- Zellweger (peroxisoma)
- Pompe
- Lesch-Nyhan
- Menkes
- PKU
306
Hypotonia, seizures, eczema, alopecia, hearing loss, retinal disease
Biotinidase Deficiency
307
Bilateral infarcts of the thalamus
Methylmalonic acidemia
308
Neonatal onset, profound DD, pili torti (kinky hair), hypopigmentation, hypotonia, Wormian bones, bladder diverticuli, death within first year
Menkes disease
309
Measure _ in any patient with unexplained lethargy or altered sensorium
Ammonia
310
Peroxisomal disorders
Zellweger, infantile Refsum, and X-linked Adrenoleukodystrophy
311
ID, painful palmoplantar hyperkeratosis, keratits (inflammation of cornea), excessive tearing, photophobia
Tyrosinemia type II
312
Normal at birth, followed by mild motor weakness, myoclonic jerks, increased startle response, decreased visual attentiveness, cherry-red spot, death by age 4
HEXB gene - Sandhoff disease, LSD
313
Severe metabolic liver disease is often associated with _
Kidney disease (renal tubular disease to renal Fanconi syndrome)
314
Orthopedic anomalies, thoracic deformity, club feet, kyphoscoliosis, thickening of mitral and aortic valves, ventricular hypertrophy. Poor eaters, respiratory difficulties, slight corneal clouding, DD, cognitive delay, happy disposition
Mucolipidosis type II (LSD)
315
How is arginase deficiency different from the other urea cycle defects?
- Neurocognitive abnormalities such as ADHD, DD/MR, and seizures
- Hepatitis and cirrhosis
- Trichorrhexis nodosa
- Systemic hypertension
316
Anorexia
UREA CYCLE
317
Frequently elevated PAA in urea cycle disorders
Glutamine, alanine and asparagine
318
Cystine precipitates and forms calculi (kidney stones) in urinary tract, renal obstruction and infection, renal insufficiency
Cystinuria
319
Abdominal pain, vomiting, dehydration, constipation, diarrhea, limb pain, peripheral neuropathy with weakness, seizures, fever, tachycardia, hypertension, fainting, sweating, depression hysteria, anxiety, paranoia.
Acute intermittent porphyria
