Clinical scenario: hypotonia | failure to thrive | macroglossia | cardiomyopathy
A 4-month-old boy is brought with progressive hypotonia, poor feeding, and failure to thrive. Examination reveals marked macroglossia, generalized muscle weakness, and hepatomegaly. Echocardiography shows hypertrophic cardiomyopathy. Plasma ammonia, blood glucose, and lactate are normal. Plasma amino acid analysis demonstrates markedly elevated lysine.
Which aminoacidopathy is the most likely diagnosis?
A. Glutaric acidemia type I
B. Hyperlysinemia
C. Maple syrup urine disease
D. Non-ketotic hyperglycinemia
E. Tyrosinemia type I
Correct answer & Explanation:
Correct Answer: B. Hyperlysinemia
Explanation
Hyperlysinemia is a rare aminoacidopathy caused by deficiency of α-aminoadipic semialdehyde synthase (AASS), resulting in impaired lysine degradation. Patients may present with hypotonia, developmental delay, seizures, and elevated plasma lysine. Although many individuals are asymptomatic, some develop cardiomyopathy and muscle weakness.
Why the other options are incorrect
- A. Glutaric acidemia type I – Caused by glutaryl-CoA dehydrogenase deficiency; presents with macrocephaly and acute dystonic crises after illness.
- C. Maple syrup urine disease – Characterized by elevated branched-chain amino acids, encephalopathy, ketosis, and maple syrup odor.
- D. Non-ketotic hyperglycinemia – Presents in the neonatal period with intractable seizures, apnea, and markedly elevated CSF glycine.
- E. Tyrosinemia type I – Causes liver failure, renal Fanconi syndrome, and elevated succinylacetone.
High-Yield Pearl
Elevated plasma lysine + hypotonia ± hypertrophic cardiomyopathy → Think Hyperlysinemia (AASS deficiency).
