Inborn Errors of Metabolism

Question 1

Respiratory alkalosis is typical of what kind of disorders?

Answer 1

Urea cycle defect

Send ammonia, stat on ice (avoid falsely elevated levels)

Question 2

Findings of primary urea cycle defect

Answer 2

Respiratory alkalosis, low BUN

Question 3

Findings of secondary urea cycle defect

Answer 3

Metabolic acidosis, high anion gap, normal/high BUN

Question 4

What is most prognostic in hyperammonemic babies?

Answer 4

DURATION of hyperammonemia matters more for prognosis than the peak level

Question 5

What is KEY in the management of hyperammonemia?

Answer 5

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

Question 6

Findings of organic acidemias

Answer 6

Primary metabolic acidosis, high anion gap

Question 7

Findings in mitochondrial disorder

Answer 7

Metabolic and lactic acidosis, elevated alanine

Question 8

Which test has the highest likelihood of diagnosing a mitochondrial disorder?

Answer 8

Nuclear mitochondrial gene panel. Also whole exome or genome sequencing

Question 9

Serum diagnostic marker for maple syrup urine disorder?

Answer 9

Alloisoleucine.

Goal of management is to control leucine levels, reverse catabolism

Question 10

Which disorder is alopecia seen with?

Answer 10

Biotinidase deficiency

Question 11

Which disorders are cataracts seen with?

Answer 11

Galactosemia, galactokinase deficiency, mevalonic aciduria

Question 12

Sweaty feet odor?

Answer 12

Isovaleric aciduria

Glutaric aciduria type 2

Question 13

Metabolic disease associated with thromboemboli?

Answer 13

Homocystinuria

Question 14

Transient neonatal hyperammonemia in preterms infants is usually due to immaturity of which enzyme?

Answer 14

Immature N-acetylglutamate synthetase activity

Question 15

Causes of normal anion gap metabolic acidosis?

Answer 15

Bicarb loss
Tyrosinemia
Galactosemia
Carbonic anhydrase deficiency
Some mitochondrial disorders of resp chain
Malnutrition

Question 16

Increased anion gap metabolic acidosis with normal lactate- next test and likely diagnosis?

Answer 16

Check urine organic acids. If abnormal then likely organic acidemia

Question 17

Increased anion gap metabolic acidosis with high lactate and abnormal urine organic acids- likely diagnosis?

Answer 17

Check urine organic acids

Abnormal: Organic acidemia or fatty acid oxidation defect

Question 18

Metabolic disorder with neutropenia and thrombocytopenia?

Answer 18

Organic acidemia

Glycogen storage disease type 1b

Question 19

Metabolic disorder with ketotic hyperglycinemia?

Answer 19

Propionate pathway abnormalities

Question 20

Urine with male cat odor?

Answer 20

3-methylcrotonyl glycinuria
Multiple carboxylase deficiency
Odor is due to 3-hydroxyisovaleric acid

Question 21

Urine with musty odor?

Answer 21

PKU because of phenylacetate

Question 22

Nitroprusside urine test

Answer 22

Homocystinuria

Question 23

Nitroanilline urine test

Answer 23

Methylmalonic aciduria

Question 24

Enzyme deficient in Type 1 glycogen storage disorder

Answer 24

Glucose 6 phosphatase

AKA von Gierke disease

Question 25

Enzyme deficient in Type 2 glycogen storage disorder

Answer 25

Lysosomal alpha-glucosidase

aka Pompe’s disease

Question 26

Only X-linked recessive urea cycle defect?

Answer 26

Ornithine carbamyl transferase

Question 27

Urea cycle defect with brittle hair?

Answer 27

Argininosuccinic lyase and acid synthetase

Question 28

Urea cycle defect with spastic diplegia

Answer 28

Arginase

Question 29

Most common urea cycle defect?

Answer 29

Ornithine carbamyl transferase

Question 30

What do cognitive outcomes in MSUD depend on?

Answer 30

Plasma leucine concentrations

Question 31

Treatment of choice for tyrosinemia?

Answer 31

Nitisinone

Question 32

Treatment for transient tyrosinemia of the newborn>

Answer 32

Ascorbic acid

Question 33

Most common etiology of homocystinuria?

Answer 33

Enzyme deficiency in the step converting homocyteine to cystathionine (cystathionine beta-synthase). Required B6.
Increased homocysteine and methionine

Question 34

Increased homocysteine, low methionine cause?

Answer 34

Deficiency of cobalamin *B12)

Question 35

Clinical symptoms of homocysteinuria?

Answer 35

Downward dislocation of lens (upward in Marfans)
Decreased joint mobility (laxity w Marfan)
Increased risk of fractures
Increased risk of large thromboses

Question 36

Findings in nonketotic hyperglycinemia

Answer 36

Agenesis of corpus callosum
Respiratory depression
Hiccups
Elevated glycine
EEG with burst suppression

Question 37

Acute management of isovaleric aciduria

Answer 37

L-carnitine and glycine administration

Question 38

PKU embryopathy is most commonly associated with?

Answer 38

Congenital heart disease: aortic coartc and HLHS

Severe cognitive impairment happens if maternal control doesnt happen till 2nd-3rd trimester

Question 39

Which glycogen storage disease presents with lactic acidosis?

Answer 39

Type 1, von Gierke’s

Also with hepatomegaly, FTT, diarrhea, bleeding issues because of liver failure

Question 40

Presentation of type 2 GSD

Answer 40

Pompe’s
Deficiency of lysosomal alpha glucosidase
Cardiomegaly

Question 41

Which urea cycle defect has low urine orotic acid?

Answer 41

Carbamyl phosphate synthetase

N-acetylglutamate synthetase

Question 42

Most common PKU finding at birth?

Answer 42

Microcephaly