Lysinuric Protein Intolerance

This is a relatively rare autosomal recessive disease¹ causing a defect in diamino acid transport. There have beem approximately 100 reported cases, mainly in Finland. Defective ornithine, lysine, and arginine transport affect the renal tubule and intestine with only minor defects of cystine transport.

There is evidence of amino acid deficiency. It is characterised chemically by renal hyperdiaminoaciduria, and by impaired formation of urea with hyperammonaemia after protein ingestion.²

• Patients thrive during breast-feeding, but ingestion of cow's milk causes diarrhoea and vomiting.
• Failure to thrive and poor appetite are common with poor growth.
• Stones do not form.
• Occasional intermittent hyperammonaemic encephalopathy occurs.
• Osteoporosis is an important part of the clinical picture, with vertebral collapse.

Diagnosis depends upon the demonstration of a failure to increase plasma lysine levels after oral lysine loads, or the ingestion of lysyl peptides.

• Symptoms can be largely prevented by a low protein diet; however, adequate calorie intake is difficult to sustain in infancy and appetite often remains poor.
• Protein restriction does not correct lysine deficiency. Long-term, low dose oral lysine supplementation has recently been found to be beneficial and well tolerated.³
• Most patients can lead a normal life with dietary restriction alone.
• Oral citrulline (2.5 to 8.5 g/day), absorbed via a different transport system, corrects ornithine and arginine deficiency and lowers plasma ammonia by priming the urea cycle. ⁴
• Acute hyperammonaemic crises are managed with intravenous (IV) glucose and intravenous or oral sodium benzoate or phenylbutyrate.
• Citrulline treatment should be maintained but intravenous citrulline is not readily available.