Lysinuric protein intolerance: Unusual clinical manifestations in a compound heterozygote with a novel pathogenic variant

TL;DR

A 10-year-old boy with lysinuric protein intolerance showed unusual symptoms and a new genetic mutation, highlighting the need for personalized treatment.

Contribution

A novel pathogenic variant in SLC7A7 is identified in a patient with lysinuric protein intolerance.

Findings

The patient exhibited severe failure to thrive and hyperammonemia with unique clinical features.

Molecular testing confirmed two pathogenic variants in SLC7A7, including a novel frameshift mutation.

Effective management involved ammonia scavengers and dietary adjustments.

Abstract

Lysinuric protein intolerance is an amino acid transport disorder that leads to episodic hyperammonemia especially in times of protein loading. We report a 10-year-old male with severe failure to thrive who presented to the hospital due to somnolence. The patient's overall appearance suggested that he was younger than his chronological age. He was admitted due to an ammonia level of 250 μmol/L that rose to 374 μmol/L on repeat testing. Mild transaminitis with AST and ALT in the 100–200 mg/dL range was noted. Plasma amino acids showed elevated glutamine, alanine, and ornithine, with diminished arginine. Urine organic acids were remarkable for elevated orotic acid. He was treated initially with D10 containing IV fluids, intralipids, and IV sodium benzoate/sodium phenylacetate and l-arginine. Once stable, he was converted to an oral ammonia scavenger-currently well controlled on sodium benzoate alone after not tolerating sodium phenyl glycerate. His diet was titrated to his meet his caloric and protein needs (with restriction) and supplementation with l-arginine, l-citrulline and l-lysine. The patient's hyperammonemia has since resolved and his glutamine has normalized. Molecular testing revealed two pathogenic variants in SLC7A7, confirming his diagnosis of lysinuric protein intolerance.

•Clinical variability underscores the need for individualized management.•c.1383_1384del (p.Ile461Metfs6): novel frameshift variant not previously reported.•c.726G > A (p.Trp242): known missense variant associated with severe LPI phenotypes.•Emphasizes the importance of characterizing novel variants.

Clinical variability underscores the need for individualized management.

c.1383_1384del (p.Ile461Metfs6): novel frameshift variant not previously reported.

c.726G > A (p.Trp242): known missense variant associated with severe LPI phenotypes.

Emphasizes the importance of characterizing novel variants.

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