IEM Flashcards
1
Q
Examples of organic acidemias
A
Methylmalonic acidemia
Propionic acidemia
Isovaleric acidemia
2
Q
Presentation of organic acidemias
A
First 2 days of life (after getting protein) with “drunk-like” intoxicated picture
3
Q
Labs of organic acidemias
A
Metabolic acidosis, high anion gap
High ammonia
Ketonuria
4
Q
Most important lab to diagnose organic acidemias
A
Urine organic acid levels
5
Q
MC fatty acid oxidation defect
A
Medium chain acyl-CoA dehydrogenase deficiency (MCAD deficiency)
6
Q
Presentation of MCAD deficiency
A
Within first 2y after period of decrease PO intake (viral gastro) – hypoglycemia, hepatomegaly, seizures
7
Q
Labs of MCAD deficiency
A
Hypoglycemia NAGMA High ammonia High LFTs NO ketones in urine NO reducing substances in urine
8
Q
Definitive diagnosis of MCAD deficiency
A
Plasma acylcarnitine profile (in NBS)
9
Q
Treatment of MCAD deficiency
A
IV 10% glucose, oral L-carnitine; avoid fasting
10
Q
Galactosemia presentation
A
First week of life: Poor feeding, FTT Hepatomegaly Hypoglycemia Lethargy Hypotonia Jaundice
11
Q
Galactosemia labs
A
Hypoglycemia
Reducing substances in urine
Urine ketones
Hyperbili
12
Q
Galactosemia enzyme deficiency
A
Galactose-1-phosphate uridyltransferase (GALT)
13
Q
Galactosemia toxic substrate
A
Deficiency in GALT –> build up of Galactose 1-P
14
Q
Diagnose galactosemia
A
Measuring GALT in RBCs
15
Q
Infection risk in galactosemia
A
Gram negative organisms (E Coli sepsis)
16
Q
Metabolic disorder with risk of Gram negative sepsis
A
Galactosemia
17
Q
Treatment of galactosemia
A
Galactose-free diet (soy formula)
NO BREASTFEEDING
18
Q
Metabolic disorder that is a contraindication to breastfeeding
A
Galactosemia
19
Q
Risk of not treating galactosemia
A
Cataracts
ID
Liver disease
20
Q
Hypoglycemia, hepatomegaly, and positive reducing substances in urine
A
Galactosemia
21
Q
Other name for glycogen storage disease type 1
A
Von Gierke Disease
22
Q
Other name for glycogen storage disease type 2
A
Pompe Disease
23
Q
Presentation of Von Gierke
A
Infant starts sleeping through the night (prolonged fasting):
Hypoglycemia (+/- seizures)
Distended abdomen, hepatomegaly
Doll-like or cherubic face
24
Q
Von Gierke labs
A
Hypoglycemia Lactic acidosis \+ Urine ketones Negative urine reducing substances Elevated TGs and cholesterol
25
Von Gierke treatment
Frequent meals/snacks, continuous NG feeds at night, cornstarch after age 2y
26
Cause of Von Gierke
Deficiency of hepatic glucose-6-phosphatase
27
Cause of Pompe
Deficiency of lysosomal breakdown of glycogen
| Deficient activity of alpha-glucosidase
28
Presentation of Pompe
Normal at birth
| One month: Floppy, FTT, HM, cardiomegaly, macroglossia, respiratory failure
29
One month old with hypotonia, hepatomegaly, cardiomegaly, macroglossia
Pompe (glycogen storage disease type II)
30
Cause of death in Pompe
Respiratory failure
31
Urea cycle defects examples and how to differentiate
1. ornithine transcarbamylase (OTC) deficiency - HIGH urine orotic acid
2. carbamoyl phosphate synthetase (CPS) deficiency - Low/Normal urine orotic acid
32
Urea cycle defects presentation
```
Hyperammonemia (encephalopathy, vomiting, lethargy, coma)
Hypotonia
Coma
No acidosis (later: resp alkalosis)
No ketosis
```
33
Urea cycle defects labs
High ammonia
No acidosis (normal pH, bicarb)
No ketosis
34
Presentation of maple syrup urine disease (MSUD)
```
Onset first week of life
Maple syrup smelling urine, ear wax
Tachypnea, shallow breathing
Lethargy, encephalopathy
Irritability
Poor feeding
Hypertonicity
Loss of Moro reflex
Seizures
Opisthotonos
```
35
MSUD labs
HAGMA
| Ketonuria
36
MSUD: elevated plasma AAs
Valine
Isoleucine
Alloisoleucine
Leucine
37
Which AA would be diagnostic of MSUD (always abnormal)
Alloisoleucine
38
Treatment of MSUD
Branched chain AA restriction:
Valine
Isoleucine
Leucine
39
Inheritance pattern of MSUD
AR
40
Inheritance pattern of homocystinuria
AR
41
Metabolic syndrome with Marfanoid-like appearance
Homocystinuria
42
Defect in homocysinuria
Cystathionine synthase deficiency
Error in methionine metabolism
Elevated serum homocysteine and methionine
Elevated urine homocystine
43
Metabolic disorder with increase risk of vascular thrombi (CVA, MI, PE)
Homocystinuria
44
Diagnose homocystinuria
Homocystine in the urine
45
Presentation of homocystinuria
```
Mild ID
Aggressive
Marfanoid appearance
DOWNward displacement of lens
Fair complexion/hair/eyes
Pectus excavatum
Limited joint mobility
```
46
Treatment of homocystinuria
Vitamin B6 (pyridoxine)
Diet low in methionine and protein
+/- Folate, B12 supplements
47
Marfan vs homocystinuria
Marfan: ANTERIOR lens displacement, normal IQ
Homocystinuria: POSTERIOR/DOWN lens displacement, mild ID
48
Inheritance pattern of PKU
AR
49
Defect in PKU
Deficiency of phenylalanine hydroxylase
Buildup of phenylalanine
Low tyrosine
50
Presentation of PKU
```
Musty/mousy odor
Light hair/skin/eyes
Eczema
Vomiting, irritability
ID
Seizures
Microcephaly
FTT
Dev delay
```
51
PKU treatment
Diet low in phenylalanine and aspartame
52
Complication of PKU treatment
You need some phenylalanine
| Over treatment is a potential problem and you can get phenylalanine deficiency (lethargy, rash, diarrhea)
53
Which AA becomes essential in PKU
tyrosine
54
Lysosomal storage disorders
Mucopolysaccharidoses: Hurler, Hunter
Sphingolipidoses: Gaucher, Tay Sachs, Niemann-Pick
55
MPS type I
Hurler
56
MPS type II
Hunter
57
Coarse facies with corneal clouding, severe ID
Hurler
58
Inheritance of Hurler
AR
59
Inheritance of Hunter
XLR
60
Features of Hurler
```
Progressive facial coarsening
Hirsutism
Corneal clouding
Severe ID
Dystosis multiplex (bone, cartilage defects)
Progressive hearing loss
Thick skin
Congenital dermal melanocytosis
Symmetric, white papules/nodules
Enlarged T/As--> obstruction--> cor pulmonale
Frequent URIs, thick secretions
Macrocephaly, thick skull
Hernias
Thickened heart valves
```
61
Lab finding in Hurler
Reduced alpha-L-iduronidase activity in WBCs
62
Lab finding in Hunter
Reduced iduronate sulfates enzyme activity in WBCs
63
Features of Hunter
```
Coarse facial features
Hepatosplenomegaly
Hearing deficits
Organomegaly
Joint contractures
"Pebbly" skin over upper back
Short stature
Cardiac: Valve dysfunction, myocardial hypertrophy
NO corneal clouding
```
64
Gaucher Disease inheritance
AR
65
Gaucher features
```
HSM
Bone pain
Easy bruisability, nosebleeds
Short stature
Myoclonic seizures
Osteosclerosis, lytic bone lesions, "erlenmeyer flask"
```
66
Gaucher labs
Thrombocytopenia
| Can be pancytopenic
67
Gaucher lab
Glucocerebrosidase activity in peripheral leukocytes
68
Tay Sachs inheritance
AR
69
Tay Sachs cause
Deficiency of hexosaminidase A activity (lysosomal enzyme)
70
Tay Sachs presentation
```
Normal until 9mo
Lethargy, hypotonia
Exaggerated startle (does not diminish with repeated stimuli)
Cherry red spot on retina
Macrocephaly
Progressive neuro deterioration
Blindness
Seizures
Death by 5yo
```
71
Populations Tay Sachs is common
Ashkenazi Jews
French Canadians
Cajuns
72
Niemann-Pick presentation
```
Hypotonia
V/d, FTT
CNS deterioration
Cherry red spot
HSM
Cause of death: respiratory failure by 2-3yo
```
73
Tay Sachs v Niemann-Pick: similarities and differences
Both:
Cherry red spot
CNS deterioration
Niemann Pick: hepatosplenomegaly
Tay Sachs: NO HSM
74
Adrenoleukodystrophy inheritance
XLR
75
Adrenoleukodystrophy presentation
```
Academic difficulty
Impulsivity
Behavioral difficulties
Gait abnormalities
Slurred speech
Hyperpigmentation
Seizures
```
76
Cause of adrenoleukodystrophy
Disorder of peroxisomal degradation of fatty acids --> accumulation of VLCFA in nervous system and adrenal glands
77
Features of glutamic academia type 1 (GA1)
AR
Macrocephaly at birth
Nml dev until stressor (fever) --> hypotonia
Subdural hematoma
Retinal hemorrhages
CT/MRI: Frontal, cortical atrophy; increased extraaxial space; degeneration of caudate nucleus and putamen
78
Menkes disease features
```
Kinky hair disease
XLR
Impaired copper absorption and transport
Marked ID
Skeletal, vascular abnormalities
Decreased copper levels
```
79
Smith-Lemli-Opitz syndrome (SLOS) features
```
AR
Disorder of cholesterol metabolism
Accumulation of 7-dehydrocholesterol
Decreased total plasma cholesterol
Microcephaly with narrow bifrontal diameter
Hypertelorism, ptosis, epicanthal folds
Cleft palate
Micrognathia
Low ears
2/3 toe syndactyly
Hypospadias, ambiguous genitalia
SGA
Strabismus, cataracts
Single transverse palmar crease
Hypoplastic L heart
```
80
Tyrosinemia type 1 features
```
Hepatorenal tyrosinemia
AR
FTT
Hepatomegaly, hepatoblastoma, liver failure
Renal dysfunction, RTA
XR findings of rickets
Increased plasma tyrosine
Increased urine succinylacetone (toxic compound)
Tx: NTBC / nitisinone
```
81
Lesch-Nyhan syndrome features
XLR (Males)
Deficiency of hypoxanthine guanine phosphoribzosyltransferase (HGPRT)
Nml at birth
By 3-6mo: FTT, hypotonia, irritable, abnormal posturing, self mutilation, dev delay
Renal stones, gout (excess uric acid)
