Lysinuric Protein Intolerance

Clinical Definition

The disease was first described in 1965. By far the highest incidence (1/60,000) is found among the Laplander descent of Finland.

Clinical Course

Because of the increased urinary excretion and decreased intestinal absorption of cationic amino acids in general and of the essential amino acid lysine in particular, the bodies of patients with lysinuric protein intolerance are progressively depleted of these amino acids.

Deficiency of ornithine subsequently leads to an impairment of the urea cycle. Affected patients experience episodes of hyperammonanemia and accordingly develop nausea and vomiting and avoid protein-rich foods.

Newborns and infants after the breast-feeding period fail to thrive, and symptoms of protein malnutrition are further aggravated by lysine deficiency.

Subsequently, patients develop hepatosplenomegaly, osteoporosis Opens in new window and bone fractures, sparse hair, muscle hypotonia, anemia Opens in new window and coagulopathies and pulmonary, renal and sometimes central nervous system disorders.

Gene Involvement

Lysinuric protein intolerance has been found to be caused by mutations in the amino acid transporter gene SLC7A7, located on chromosome 14q.

In patients with lysinuric protein intolerance, the plasma concentration of cationic amino acids in plasma is low and the concentrations of glutamine, alanine, serine, proline, citrulline and glycine may be elevated.

The urinary excretion of lysine is excessive and that of arginine and ornithine is also elevated. Serum ammonia increases after protein-containing meals but is normal under fasting conditions.

Several cases of pancreatitis have been reported in patients with lysinuric protein intolerance, and the morphologic alterations in the pancreas can include inflammatory changes, necrosis, intraductal protein plugs, atrophy and fibrosis.

The underlying defect is thought to be the severe protein deficiency, because similar pancreatic changes have been found in patients with kwashiorkor.

In at least one kindred that was previously classified as having familial pancreatitis, the underlying cause may have been either primary lysinuric protein intolerance or co-inheritance of lysinuric protein intolerance together with one of other gene mutations that predispose to familial pancreatitis.

Therapeutics

Patients with lysinuric protein intolerance are treated with a proten-restricted and citrulline-supplemented diet and usually respond with an improvement of symptoms, although the aversion to dietary proteins remains.

Patients with lysinuric protein intolerance-associated pulmonary disease, but not with renal complications, have been reported to respond to steroids.