Lysinuric protein intolerance (SLC7A7 gene): symptoms, inheritance and diet

Proteins in food are broken into amino acids, which the body then absorbs and reuses. In lysinuric protein intolerance, the transport of three of them, lysine, arginine and ornithine, does not work properly. MedlinePlus, which is produced in the United States, describes the condition as a disorder caused by the body's inability to digest and use these amino acids, which are found in many protein-rich foods, so that nausea and vomiting typically follow eating protein.

The transporter that fails is found in the lining of the intestine and in the kidneys, and also in immune cells. A published research paper explains that the amino acids are poorly absorbed from the gut and lost in the urine, so blood levels are low, and that lung, liver, immune system, muscle and brain are affected to varying extents.

It is a rare condition. MedlinePlus estimates about 1 in 50,000 newborns in Finland, where it is most frequent, with cases also in Japan and Italy and less frequent elsewhere. A recent case report states that over 200 cases have been reported worldwide.

The SLC7A7 gene provides instructions for a protein called y+L amino acid transporter 1. MedlinePlus says variants in this gene disrupt the movement of lysine, arginine and ornithine, so these amino acids are not absorbed in the small intestine and are lost in urine in the kidneys.

Inheritance is autosomal recessive. Both copies of the gene in each cell carry variants, and each parent usually carries one changed copy without having signs or symptoms. Genomics England's PanelApp lists SLC7A7 as a green, or diagnostic-grade, gene on its hyperammonaemia and other panels, with a biallelic mode of inheritance.

Researchers have also found that some people have large deletions rather than single-letter changes in the gene, so laboratory testing methods need to look for both types of change.

A research paper notes that people are usually well while breastfed and that symptoms appear only after weaning. After infancy they tend to reject protein-rich food and show delayed growth, thin bones, an enlarged liver and spleen and low muscle tone. Most have normal mental development.

MedlinePlus lists short stature, muscle weakness, impaired immune function and brittle bones prone to fracture. A lung condition called pulmonary alveolar proteinosis can develop, in which protein deposits interfere with lung function, and the kidneys can be affected, with end-stage kidney disease reported in some people. Very high ammonia for too long can cause coma and intellectual disability.

Because people may unconsciously avoid protein, a case report describes that some remain symptom-free for longer and that this can delay diagnosis. The same report describes a child whose ammonia rose after his protein intake was suddenly increased to treat poor growth, which shows why the diagnosis matters.

A research paper explains that the condition is diagnosed by high urinary excretion of the dibasic amino acids, especially lysine, with low plasma levels of these amino acids. The typical amino acid profile in blood can look like a urea cycle disorder, with low citrulline and arginine, and ammonia may be raised.

Genetic testing of the SLC7A7 gene confirms the diagnosis, and a case report emphasises that testing can add information even when biochemical tests have already given the answer. In the NHS, testing for rare metabolic conditions is arranged through specialist metabolic and genetics services.

A research paper states that patients are treated with a low-protein diet and supplementation with L-citrulline, a urea cycle intermediate that is absorbed by other transporters and helps to correct the urea cycle deficiency. Low-dose oral lysine supplementation is reported as potentially beneficial when started at an early age.

A published case describes management of a high-ammonia episode in hospital with intravenous medicines that help the body clear ammonia, together with arginine and protein restriction, and long-term care using a restricted total protein intake, specialised amino acid formula and supplements, with the dose individually titrated. The case report emphasises that management needs to be individualised because the presentation is so variable.

Clinical teams also monitor for lung, kidney, bone and immune complications. A review abstract in the Journal of Human Genetics notes that treatment can prevent high-ammonia episodes to some extent but that progression of lung and kidney complications cannot be prevented, which is why regular screening matters.

No NHS patient leaflet specific to this condition was found when this guide was written, so the information above comes from United States and international clinical sources and should be treated as general background. In the UK, care is led by a specialist inherited metabolic disease service, usually with a metabolic dietitian, and the charity Metabolic Support, whose website describes support for people living with an inherited metabolic disorder, may be a useful contact.

Anyone who has recurrent vomiting after protein-rich meals, drowsiness or confusion after eating, or a child with poor growth and food aversion should see their GP. Sudden confusion, drowsiness that is hard to rouse or seizures need emergency help through 999.