Metabolics - NBS (TRANSFERRED)

Question 1

Reference: Genetics residents in-training examination – Fall 2020

You receive a referral to follow up on an abnormal newborn screening result – an infant with elevated succinylacetone in a dried bloodspot. This finding has been confirmed on a second blood sample.

a) Identify the most likely diagnosis, and name the enzyme involved.
b) Describe the typical plasma amino acid profile and urine organic acid profile of a patient affected by this disorder.
c) Suggest ‘routine’ lab tests which you would expect to give abnormal results in an acutely ill patient with this disorder.
d) What are the two currently accepted treatments for this condition?

Answer 1

a) Tyrosinemia type 1; fumarylacetoacetate hydrolase

b)
PAA: most commonly elevated tyrosine, methionine, possibly phenylalanine
UOA: elevated excretion of 4-hydroxyphenyllactate, 4-hydroxyphenylpyruvate, 4- hydroxyphenylacetate, and succinylacetone

c)
AFP, PT/PTT/INR, liver enzymes, bilirubin

d)
Dietary tyrosine restriction and NTBC (inhibits 4-HPPD, an enzyme higher up in the tyrosine metabolic pathway).