Inborn Errors of Metabolism

Question 1

PKU

Answer 1

• Phenylketonuria
• AR on newborn screening
• No/defective/little of PAH enzyme (phenylalanine hydroxylase) which turns phenylalanine into TYROSINE
• Presentation: intellectual disability, stunted growth, SZ, fair skin, musty body odor, hard to manage eczema
• Tx: dietary restrictions (avoid aspartame artificial sweetener), and add Tyrosine
• Can also be caused by decreased necessary tetrahydrobiopterin cofactor (BH4) –> tx with more BH4
• Maternal PKU –> unk PKU in mom –> microcephaly, ID, CHDefects, stunted growth
• Permenant if not tx quickly

Question 2

MSUD

Answer 2

-Maple Syrup Urine Dz
-AR on newborn screening
-increase in Alpha ketoacids = Leucine&raquo_space; isoleucine and valine
-Severe CNS defects, ID, death
-Tx: dietary restrictions of alpha-ketoacids (limit protein intake) + thiamine supplement. Liver transplant if need
-Classic presentation = newborn vomiting, poor feeding, irritable, with sweet smelling urine
I Love Vermont maple syrup = Isoleucine, Leucine, and Valine

Question 3

Tryosinemia T1

Answer 3

• Hepatorenal tyrosinemia
• due to decreased FAH enzyme
• Presentation: acute liver failure in infant, hyperbilirubinemia, jaundice, ascites, hepatomegaly, Rickets, hepatocellular carcinoma in infant
• Tx: NTBC
• Dx: succinylacetone in urine

Question 4

Homocystinuria

Answer 4

-AR
Multiple causes
1)Defect in cystathionine synthase enzyme
2) less active cystathionine synthase –> tx with B6 (is a cofactor)
-Get elevated Homocysteine –> MARFANOID HABITUS, intellectual disability, osteoporosis, myopia, and THROMBOEMBOLISM (stroke and MI)
-Dx homocysteine in blood and urine

Question 5

Hyperammonemia

Answer 5

Acute: encephalopathy, SZ, ataxia, hallucinations, vomiting, decreased appetite
-neonates = temp instability, hyperventilation

Chronic: mild developmental delay, FTT, protein avoidance, anxiety, depression, liver damage, migraines

Question 6

OTC Deficiency

Answer 6

-XLR
-Ornithine Transcarbamylase enzyme converts Ornitine + carbamoyl phosphate into Citruline
-Most common urea cycle defect
-OTC gene only expressed in liver
-Often lethal to neonates –> need dialysis and liver transplant
Tx: ammonia scavengers, dietary restrictions (lowest of all low protein diets), supplemental: citruline or arginine, essential AA, dialysis and liver transplant if need