Lysinuric protein intolerance


Lysinuric protein intolerance is an autosomal recessive metabolic disorder affecting amino acid transport.
About 140 patients have been reported, almost half of them of Finnish origin. Individuals from Japan, Italy, Morocco and North Africa have also been reported.

Signs and symptoms

s with LPI are usually symptom-free when breastfed because of the low protein concentration in human milk, but develop vomiting and diarrhea after weaning. The patients show failure to thrive, poor appetite, growth retardation, enlarged liver and spleen, prominent osteoporosis and osteopenia, delayed bone age and spontaneous protein aversion. Forced feeding of protein may lead to convulsions and coma. Mental development is normal if prolonged episode of hyperammonemia can be avoided. Some patients develop severe pulmonary and kidney complications. High levels of plasma glutamine and glycine are observed.

Causes

It has been associated with SLC7A7.

Mechanism

In LPI, urinary excretion of cationic amino acids is increased and these amino acids are poorly absorbed from the intestine. Therefore, their plasma concentrations are low and their body pools become depleted. Deficiency of arginine and ornithine restricts the function of the urea cycle and leads to hyperammonemia after protein-rich meals. Deficiency of lysine may play a major role in the skeletal and immunological abnormalities observed in LPI patients.

Diagnosis

The diagnosis is based on the biochemical findings and the screening of known mutations of the causative gene from a DNA sample.

Treatment

Treatment of LPI consists of protein-restricted diet and supplementation with oral citrulline. Citrulline is a neutral amino acid that improves the function of the urea cycle and allows sufficient protein intake without hyperammonemia.

Prognosis

Under proper dietary control and supplementation, the majority of the LPI patients are able to have a nearly normal life. However, severe complications including pulmonary alveolar proteinosis and chronic kidney disease may develop even with proper treatment.
Fertility appears to be normal in women, but mothers with LPI have an increased risk for complications during pregnancy and delivery.