Inborn Errors of Metabolism Flashcards
Respiratory alkalosis is typical of what kind of disorders?
Urea cycle defect
Send ammonia, stat on ice (avoid falsely elevated levels)
Findings of primary urea cycle defect
Respiratory alkalosis, low BUN
Findings of secondary urea cycle defect
Metabolic acidosis, high anion gap, normal/high BUN
What is most prognostic in hyperammonemic babies?
DURATION of hyperammonemia matters more for prognosis than the peak level
What is KEY in the management of hyperammonemia?
Energy (key to switching from catabolic to anabolic state). High dextrose +/- insulin, intralipids
Hydration and ammonia scavengers are also important, but they clean up the ammonia- they don’t switch to anabolic state
Findings of organic acidemias
Primary metabolic acidosis, high anion gap
Findings in mitochondrial disorder
Metabolic and lactic acidosis, elevated alanine
Which test has the highest likelihood of diagnosing a mitochondrial disorder?
Nuclear mitochondrial gene panel. Also whole exome or genome sequencing
Serum diagnostic marker for maple syrup urine disorder?
Alloisoleucine.
Goal of management is to control leucine levels, reverse catabolism
Which disorder is alopecia seen with?
Biotinidase deficiency
Which disorders are cataracts seen with?
Galactosemia, galactokinase deficiency, mevalonic aciduria
Sweaty feet odor?
Isovaleric aciduria
Glutaric aciduria type 2
Metabolic disease associated with thromboemboli?
Homocystinuria
Transient neonatal hyperammonemia in preterms infants is usually due to immaturity of which enzyme?
Immature N-acetylglutamate synthetase activity
Causes of normal anion gap metabolic acidosis?
Bicarb loss Tyrosinemia Galactosemia Carbonic anhydrase deficiency Some mitochondrial disorders of resp chain Malnutrition
Increased anion gap metabolic acidosis with normal lactate- next test and likely diagnosis?
Check urine organic acids. If abnormal then likely organic acidemia
Increased anion gap metabolic acidosis with high lactate and abnormal urine organic acids- likely diagnosis?
Check urine organic acids
Abnormal: Organic acidemia or fatty acid oxidation defect
Metabolic disorder with neutropenia and thrombocytopenia?
Organic acidemia
Glycogen storage disease type 1b
Metabolic disorder with ketotic hyperglycinemia?
Propionate pathway abnormalities
Urine with male cat odor?
3-methylcrotonyl glycinuria
Multiple carboxylase deficiency
Odor is due to 3-hydroxyisovaleric acid
Urine with musty odor?
PKU because of phenylacetate
Nitroprusside urine test
Homocystinuria
Nitroanilline urine test
Methylmalonic aciduria
Enzyme deficient in Type 1 glycogen storage disorder
Glucose 6 phosphatase
AKA von Gierke disease
Enzyme deficient in Type 2 glycogen storage disorder
Lysosomal alpha-glucosidase
aka Pompe’s disease
Only X-linked recessive urea cycle defect?
Ornithine carbamyl transferase
Urea cycle defect with brittle hair?
Argininosuccinic lyase and acid synthetase
Urea cycle defect with spastic diplegia
Arginase
Most common urea cycle defect?
Ornithine carbamyl transferase
What do cognitive outcomes in MSUD depend on?
Plasma leucine concentrations
Treatment of choice for tyrosinemia?
Nitisinone
Treatment for transient tyrosinemia of the newborn>
Ascorbic acid
Most common etiology of homocystinuria?
Enzyme deficiency in the step converting homocyteine to cystathionine (cystathionine beta-synthase). Required B6.
Increased homocysteine and methionine
Increased homocysteine, low methionine cause?
Deficiency of cobalamin *B12)
Clinical symptoms of homocysteinuria?
Downward dislocation of lens (upward in Marfans)
Decreased joint mobility (laxity w Marfan)
Increased risk of fractures
Increased risk of large thromboses
Findings in nonketotic hyperglycinemia
Agenesis of corpus callosum Respiratory depression Hiccups Elevated glycine EEG with burst suppression
Acute management of isovaleric aciduria
L-carnitine and glycine administration
PKU embryopathy is most commonly associated with?
Congenital heart disease: aortic coartc and HLHS
Severe cognitive impairment happens if maternal control doesnt happen till 2nd-3rd trimester
Which glycogen storage disease presents with lactic acidosis?
Type 1, von Gierke’s
Also with hepatomegaly, FTT, diarrhea, bleeding issues because of liver failure
Presentation of type 2 GSD
Pompe’s
Deficiency of lysosomal alpha glucosidase
Cardiomegaly
Which urea cycle defect has low urine orotic acid?
Carbamyl phosphate synthetase
N-acetylglutamate synthetase
Most common PKU finding at birth?
Microcephaly
