IEM Flashcards
Zellweger spectrum disorder
hepatocerebrorenal syndrome
neonatal adrenoleukodystrophy
decreased peroxisomal function leading to limited oxidation of long chain FA
prominent forehead, wide open fontanel, epicanthal folds, hypertelorism, broad and flat nasal bridge, micrognathia
hypotonia, poor feeding, cataracts, chondrodysplasia punctate, renal cortical microcysts
Labs:
absent/decreased peroxisomes
increasee VLC FA (C22, C24, C26) NBS
supportive treatment geared towards symptoms
death usually by 1 year of age
Urea cycle
infants with galactosemia are at risk for infections with ___
E.Coli!
what to do if you have hyperammonemia
pathway for hypoglycemia workup
Maple syrup urine disease
MSUD
AR
branched chain amino acids (leucine, isoleucine, valine) cannot be broken down beyond the alpha-ketoacids
normal at birth, symptoms within first few days to weeks
poor feeding, vomiting, lethargy tachypnea
by 4 days: alternating lethargy/irritability, hypotonia/hypertonia, dystonia, apnea, seizures, signs of cerebral edema
Labs:
- KETONURIA
- MAPLE SYRUP SMELL IN URINE = ketoacids
- METBOLIC ACIDOSIS
- hypoglycemia
Tests:
- urine dinitrophenylhydrazine test: + white precipitates
if breastfeeding, may delay symptoms until 4-10 days of age
Methylmalonic aciduria
MMA
deficiency of methylmalonyl-CoA isomerase
required cobalamin/Vit B12
increased risk of bacterial infections, FTT
dyspmorphic features (some): high forehead, broad nasal bridge, epicantahl folds, smooth philtrum, triangular mouth
vomiting, dehydration, lethargy, hepatomegaly
labs: metabolic acidosis (incr anion gap), ketonuria, hypocalcemia, increased lactate
NEUTROPENIA/THROMBOCYTOPENIA
normal to low glutamine
HYPERAMMONEMIA- can have resp alkalosis–> mistake for UCD
this has more severe neurologic outcomes
likely renal transplant
PKU
Phenylketonuria
typical insidious onset in early infancy
MUSTY OR MOUSY URINE ODOR
diagnosis: urine detection of phenylpyruvic acid = +blue-green color
low phe diet
liver transplant leads to complete correction
outcome depenent on age of diagnosis/management
- BEST OUTOME if control by 2 weeks of age
classic: if initiate low phe diet within 1st 3 weeks, may have close to normal intelligence
affects of maternal PKU on infant
IUGR
brain growth
myelination
neutrotransmitter synthesis
increased risk fo CHD
what direction of lens subluxation in homocystinuria
DOWNWARD
upward= Marfan’s
what cofactor helps in pyruvate carboxylase deficiency
biotin
glycogen storage disease presenting with lactic acidosis, hypoglycemia, hepatomegaly
von Gierke
GLUCOSE-6-PHOSPHATASE
possible bleeding diathesis secondary to liver failure
increased risk for infection
poor prognosis
mode of inheritance for OTC deficiency
x-linked recessive
Niemann-Pick disease type A
lysosomal storage disease
first month of life with HSM, nervous system deterioration
macular cherry red spot, clear cornea, foam cells on bone marrow biopsy
A+B due to sphingomyelinase defect
type B = no eye or CNS involvement
Gaucher disease type I/II
Ashkenazi Jewish descent
defects in enzyme glucocerebrosidase
HSM and neurologic manifestations
NO EYE INVOLVEMENT
bone marrow biopsy = Gaucher cells
pyruvate dehydrogenase deficiency
mitochondrial disorder
presents in childhood with developmental delays, poor muscle tone/weakness, seizures, ataxia or choreoathetosis, GLOBAL CEREBRAL ATROPHY
ABSENT CORPUS CALLOSUM
labs:
anion-gap metabolic acidosis
elevated lactate and pyruvate
assessing abnormal enzyme activity in white blood cells or skin fibroblasts
no treatment, uniformly fatal
triad for urea cycle defect presentation
hyperammonemia
primary respiratory alkalosis
normal serum glucose
non-ketotic hyperglycinemia
lethargy
hypo or hypertonia
seizures
obtundation
respiratory failure
HICCUPS
absent corpus callosum
EEG with burst suppression –> hypsarrhythmia
elevated urin, blood, CSF glycine
no reliably effective treatment, poor prognosis
ketotic hyperglycinemia
aka propionic aciduria
AR
deficiency of propionyl-CoA carboxylase deficiency
similar presentation to non-ketotic hyperglycinemia but NO ketones in urine/blood
homocystinuria
AR
DOWNWARD dislocated lens
risk for osteoporosis, seizures, thrombosis
elevated methionine and homocystinuria
deficiency in either vitamin 12 dependent factors or cystathionine synthetase
treat by supplementing with pyridoxine, cysteine, folate
limiting dietary methionine
Boy with golden-brown granular pigementations on his cornea, difficulty speaking, abnormal jerky movements of his extremities. Also has liver disease
Dx: Wilson’s disease- inability to transport copper to the liver = copper deposition in liver, cornea, basal ganglia, renal tubules
Tx: D-penicillamine- chelates copper to reduce serum levels
brittle, kinky, steely hair
Menke’s disease
defect in the membrane copper transport channel leading to poor absorption and cellular distribution of copper
Tx: copper injections
Defect in Gaucher I/II
Glucocerebrosidase
Defect in Niemann Pick A/B
sphingomyelinase
Defect in Tay Sachs
Hexosaminidase-A
Defect in Fabry disease
alpha- galactosidase
Defect in Krabbe disease
Beta-galactosidase
exclusively breastfed baby just introduced to formula now with new onset seizure, vomiting, poor PO
had been normal prior
labs: hypoglycemia, elevated LFTs, +urine reducing substances
fructosemia!
deficiency in fructose-1-phosphate aldolas = cant breakdown fructose
BM= lactose = galactose + glucose
Cow’s milkd formula= sucrose = fructose +glucose
galactosemia- presents after ANY feeding introduced
where does the metabolic acidosis come from in galactosemia?
results from renal tubular dysfunction NOT from excessive lactate concentrations
infant with poor feeding, vomiting in first 2-3 days, lethargy, jaundice, hepatomegaly, liver failure, renal tubular dysfunction
galactosemia
absence of galactose-1-phosphate-uridyltransferase
cant break down galactose into glucose
NON-GLUCOSE reducing substances in urine
occurs in both formula and BM fed babies
cataracts occur after 2 weeks of age due to excess galactilol but regress with good dietary control of lactose
increased risk of E.coli sepsis
liver issues can progress to cause coagulopathy and hypoalbuminemia
infant with symmetric muscle weakness, cardiomegaly, congestive heart failure (big heart on CXR). Poor prognosis with death typically at < 1 year
Pompe’s Disease
glycogen storage disease due to deficiency of lysosomal alpha-glucosidase
infant with glycogen storage disease. Affects liver, kidney, GI track
spares muscle and brain
von Gierke disease
deficiency in glucose-6-phosphatase
