Inborn Errors Metabolism

Question 1

At presentation, general way to distinguish between
metabolic disorders with intoxication affects vs
metabolic disorders with energy deficiencies

Answer 1

metabolic disorders with intoxication effects initially asymptomatic

metabolic deficiencies with energy deficiencies usually symptomatic at birth

Question 2

Why might you see transient neonatal hyperammonemia in preterm infants?

Answer 2

immature N-acetylglutamate synthase activity.

Question 3

If there is hyperammonemia, what do you assess for?

Answer 3

Acidosis and ketonuria

Question 4

If acidosis and Ketonuria possible causes?

Answer 4

can be various acidemias, Pyruvate carboxylase deficiency, or B-methlcrtonyl glycinuria

Question 5

If elevated ammonia with no acidosis, no ketonuria, what do you assess for next?

Answer 5

Plasma citrulline levels
(urea cycle defect?)

Question 6

If elevated ammonia, with acidosis and ketonuria, what is it?

Answer 6

Fatty acid oxidation abnormality.

Question 7

In unexplained hypoglycemia what’s next laboratory assessment

Answer 7

Assess for non-gluose reducing substances

Question 8

If non-glucose reducing substances are absent in hypoglycemia, what is next lab assessment?

Answer 8

check for urine ketones

Question 9

What lab abnormality will you see in Fatty acid oxidation defect?

Answer 9

increased free fatty acids
(there will be no acidosis)
hypoketotic, hypoglycemia

Question 10

Galactose-1-phosphate-uridyl transferase (GALT) absent what is disorder?

Answer 10

Classic Galactosemia

Question 11

Why are there cataracts in galactosemia?

Answer 11

fetal exposure to galactose, excess galacititol in eyes

Question 12

Laboratory findings in galactosemia?

Answer 12

elevated LFTS, low glucose, decrease coagulation factors, hyperchloremic metabolic acidosis

Question 13

Two types of Neonatal Glycogen Storage Diseases?

Answer 13

Type 1 (Von Gierke)
Type II (Pompe)

Question 14

What are organs are effected in Glucose 6-phosphatase deficiency?
(von Gierke)

Answer 14

Liver, Kidney GI
(you will see lactic acidosis)

Question 15

What are organs are effected in lysosomal glucosidase deficiency?
(Pompe)

Answer 15

All organs, especially muscles and nerves
also see cardiomegaly and CHF

Question 16

Laboratory findings urea cycle defects?

Answer 16

hyperammonia, respiratory alkalosis, normal glucose

Question 17

What is most common urea cycle defect?

Answer 17

Ornithine carbamyl transferase

Question 18

Laboratory abnormalities seen in OCT defiency?

Answer 18

Hyperammonemia, elevated urine orotic acid, decreased citrulline, decreased arginine.

Question 19

All urea cycle defects have what laboratory abnormalities in common?

Answer 19

high glutamine and alanine.

Question 20

Which urea cycle defect presents with spastic diplegia?

Answer 20

arginase deficiency

Question 21

Why would you consider lactulose diet in urea cycle defect?

Answer 21

intestinal bacteria changes lactulose to lactic acid and low ph inhibits absoprtion of ammonia

Question 22

Treatment of urea cycle defects and hyperammonemia

Answer 22

goal to remove nitrogen via medications
sodium benzoate, sodium phenylacetate

these meds create pathways to excrete nitrogen precursors

Question 23

In urea cycle disorders supplent with what amino acid?

Answer 23

Arginine
(with lone exception of arginase deficiency) as arginine will become essential amino acid in these disorders

Question 24

How do organic acidemias present? How does that differ than urea cycle defects?

Answer 24

ogranic acidimeas:
hypoglycemia, severe acidosis, ketosis

urea cycle
normal or slightly increased glycemia, mild acidosis (lactate), absent ketonuria

Question 25

What are symptoms of Galctosemia Type II (galactokinase deficiency)

Answer 25

bilateral cataracts, developmental disability, pseudotumor cerebri

Question 26

How do sodium benzoate and phenylbutarate work?

Answer 26

combine with glycine and glutamate respectively which leads to excretion of amino acids (involved in urea cycle) and allows for nitrogen excretion

Question 27

when do you see elevated succinylacetone?

Answer 27

seen in transient tyrosinemia
or Hereditary Tyrosenimia type 1

Question 28

what causes PKU

Answer 28

defect in enzyme phenylane hydroxylase leading to accumulation of phenylanaline derivatives.

Question 29

Signs of PKU

Answer 29

delayed milestones, microcephaly, hypopigemntation, hyperactivity, seizrues, and musty order to skin

Question 30

How does Nitisinone work?

Answer 30

works by inhibiting enzyme 4-hydroxyphenylpyruvate dioxygenase.

This enzyme is involved in degrading tyrosine to other toxic metabolites, which are responsible for disease-related symptoms.

Question 31

Features of OTCD deficiency

Answer 31

elevated plasma alanine and glutamine levels
elevated urine orotic acid levels

plasma citrulline, arginine, and BUN levels decreased

Question 32

The presence of lactic acidosis distinguishes these disorders from the organic acidemias?

Answer 32

Disorders of pyruvate metabolism
(carboxylase or dehydrogenase deficiency)

Question 33

how do urea cycle defects present?

Answer 33

hyperammonia without acidosis

Question 34

How/why is carnitine used?

Answer 34

fatty acid oxidation defects
not urea cycle disorders

Question 35

how quickly do urea cycle defects present

Answer 35

24 hours

Question 36

Where does metabolism of branch chain amino acids occur?

Answer 36

in the muscle

Question 37

If there is hyperammonia and no acidosis, what is likely disorder?

Answer 37

probably urea cycle defect/ specific amino acid disorder

Question 38

Important clues for fatty oxidation disorders in infancy?

Answer 38

elevated CPK and uric acid
with hypoketotic hypoglycemia

Question 39

Other than diet restriction what can be helpful supplement in non-classical PKU?

Answer 39

5-Hydroxytryptophan
(bypasses block in serotonin synthesis)
serotonin requires tetrahydrobiopetrin

Question 40

What is defect in branched chain amino acid disease (MSUD)?

Answer 40

BCKAD responsible for decarboxylation of respective alpha ketoacids, in MSUD their is defect in this and abnormal accumulation of alpha ketoacids, leading to symptoms