Amino acidopathies

Question 1

Presentation of PKU

Answer 1

1 yo child of normal pregnancy and delivery shows developmental delay, light hair, eczema, UNFAMILIAR ODOR, seizures

Question 2

Diagnosis of PKU

Answer 2

urine ferric chloride spot test

Question 3

Cause of PKU

Answer 3

autosomal recessive deficiency of hepatic phenylalanine hydroxylase –> hyperphenylalaninemia

Question 4

Newborn screening of PKU

Answer 4

bacterial inhibition assay using dried blood spots

Question 5

PKU phenotype

Answer 5

hyperphenylalaninemia, MR and autistic behaviors, white matter hyperintensities (pseudoleukodystrophy), seizures

Question 6

Therapies for PKU

Answer 6

restrict Phe intake (do not eliminate)

biopterin, large neutral amino acid supplement, phenylalanine ammonia lyase

Question 7

Maternal PKU syndrome

Answer 7

microcephaly, low birth weight, mental retardation, and malformations in infants of mothers with poorly controlled PKU

Question 8

what amino acids are elevated in Maple Syrup Urine Disease?

Answer 8

Branched-chain amino acids (leucine, valine, isoleucine)

leucine&raquo_space;> valine and isoleucine

Due to branched chain ketoacid dehydrogenase deficiency

Question 9

What amino acid is responsible for the unique smell in MSUD?

Answer 9

2-hydroxyisoleucine

Question 10

MSUD inheritance

Answer 10

autosomal recessive

Question 11

A mutation in which subunit of BCKD is likely to be responsive to thiamine (vitamin B1)?

Answer 11

E2 subunit

Question 12

3 presentations of MSUD

Answer 12

severe neonatal form (less than 1% residual enzyme) = few abnormal routine labs, maple syrup odor in urine (2-hydroxyisoleucine)

acute intermittent form (with residual enzyme activity) = late onset, ataxia, ketoacidotic coma c hypoglycemia, amino acids and keto acids can be normal between attacks

subacute chronic form (with residual enzyme activity) = hypotonia and developmental delay, failure to thrive, spastic paraplegia

Question 13

Acute treatment of MSUD

Answer 13

eliminate dietary BCAA protein, supplement valine and isoleucine

avoid hypotonic fluids, treat cerebral edema, hemodialysis?

Question 14

Tyrosinemia type 1

Answer 14

autosomal recessive fumarylacetoacetate hydrolase (FAH) deficiency

Question 15

Tyrosinemia type 1 presenting forms

Answer 15

Early infancy: 1-6 months. hepatic failure or cholestatic jaundice or cirrhosis with renal tubulopathy

Late infancy: rickets due to renal tubulopathy (Fanconi syndrome) with no obvious liver failure

Porphyria-like attack at any age (CAN BE PRESENTING SIGN)

Question 16

Tyrosinemia type 1 urine organic acid elevations

Answer 16

succinylacetone and d-ALA

Question 17

Treatment of tyrosinemia type 1

Answer 17

Phe and Tyr restiction + NBTC.

liver transplant if HCC develops

Question 18

Clinical features of tyrosine disorders

Answer 18

cirrhosis –> abd enlargement and ascites

“rachitic rosary” along costochondral joints

palmoplantar keratosis

corneal lesions

Question 19

Homocystinuria

Answer 19

autosomal recessive cystathione B-synthase deficiency

50% are pyridoxine (B6) responsive

Question 20

Diagnostic eval of homocystinuria

Answer 20

plasma amino acids –> high methionine, homocysteine and total homocysteine

urine amino acids –> high homocysteine (normally undetectable)

Urine organic acids: normal

Question 21

Treatment of homocystinuria

Answer 21

Pyridoxine (B6) challenge: 750mg PO per day for one week, while monitoring plasma methionine and total homocysteine

restict dietary protein, supplement with Met-free foods, oral betaine