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Lysinuric protein intolerance (LPI) is a rare autosomal recessive disorder affecting the basolateral transporter for cationic amino acids in the kidney and intestine leading to deficiency of these amino acids in blood (1,2). Low levels of arginine and ornithine limit the functioning of the urea cycle resulting in high levels of ammonia accumulation affecting the brain and other organs.

A three year old child born following a consangineous relationship had presented to us with an eight month history of daily episodic irritability lasting for upto 12 hours. There was associated slow cognitive regression. The child was being treated for epilepsy with multiple anticonvulsants without benefit.

His EEG was normal and MRI had shown symmetrical periventricular T2 Hyperintensities. On clinical examination he was pale, ataxic and had hepatosplenomegaly. His plasma ammonia was significantly raised at 840 micromol/l (normal range <35) as were plasma ferritin with mild derangment of liver function. Clinically Lysinuric proteinuric intolerance was suspected.

Plasma amino acids showed low levels of lysine, arginine and ornithine while urine aminoacidogram showed elevated level of these aminoacids.Urine organic acids were analyzed by GC-MS which demonstrated elevated levels of orotic acid (around 460 fold).

The child showed dramatic improvement in his symptomatology after starting ammonia scavanging therapy ( Sodium benzoate and Citrulline) and mild protein restriction in  diet. Ammonia levels had normalised.

The clinical and biochemical investigations are consistent with the diagnosis of LPI and gene studies subsequently confirmed a homozygous c.158C>T mutation in exon 1 of the gene for LPI

lysinuric proteinuria, regression, ammonia