Lysinuric Protein Intolerance - A Rare Metabolic Disorder

Introduction

Lysinuric protein intolerance (LPI) is a rare genetic condition due to the body's inability to digest and use specific amino acids, arginine, lysine, and ornithine. Amino acids are considered the building block of proteins. Thus, the failure of the body cells to digest and use these amino acids present in protein-rich foods causes protein indigestion, and the individual may develop symptoms like nausea and vomiting. Lysinuric acid intolerance occurs approximately in 1 in 57,000 to 60,000 newborns in Finland and Japan. It occurs less frequently in other populations, and the exact incidence rate is unknown.

What Is Protein Intolerance?

Protein intolerance is a metabolic disorder caused by the inability to break down and digest amino acids in the body effectively. When protein-rich food items are not digested properly, they act as antigens and induce food protein allergies in the body. It may occur due to genetic, metabolic, immunologic, non-immunologic, and pharmacological causes. The affected individuals mainly present with gastrointestinal symptoms, including abdominal pain, vomiting, bloating, and excessive intestinal gas.

What Is Lysinuric Protein Intolerance?

Lysinuric protein intolerance (LPI) is a genetic metabolic disorder that affects amino acid metabolism. Half of the patients reported with lysinuric protein intolerance are of Finnish origin. In addition, individuals from Italy, Japan, North Africa, and Morocco have also been reported with lysinuric protein intolerance. This metabolic condition usually presents in infants after they are weaned from breast milk or formula milk.

Infants with lysinuric protein intolerance do not show symptoms during breastfeeding because of low protein concentration in breast milk. However, after weaning (starting with other food items), the infants begin developing vomiting and diarrhea. The affected individuals may initially develop gastrointestinal symptoms and produce systemic side effects such as enlarged spleen and liver, delayed bone maturation, osteoporosis, and convulsions. In addition, some patients may develop severe kidney and pulmonary complications leading to coma.

What Are the Causes of Lysinuric Protein Intolerance?

Lysinuric protein intolerance (LPI) is a genetic disease caused by mutations in the SLC7A7 gene. This gene provides instructions for protein synthesis and involves the transport of amino acids, arginine, lysine, and ornithine in the body cells. The effective transfer of amino acids from the small intestine and kidneys to other body parts is necessary to use proteins. Mutations in the SLC7A7 gene disrupt amino acid metabolism leading to a shortage of arginine, lysine, and ornithine and their abnormal levels in the urine.

Shortage of arginine, lysine, and ornithine disrupts several vital functions in the body. Ornithine and arginine are involved in many cellular processes, including the urea cycle, which involves urea production from ammonia. The disruption of the urea cycle due to a lack of ornithine and arginine causes elevated ammonia levels in the blood and health effects. Lysine is seen abundantly in collagen molecules, the vital constituent of connective tissues, tendons, and ligaments. A shortage in lysine levels causes defects in bone maturation and deformities.

How Is Lysinuric Protein Intolerance Inherited?

Lysinuric protein intolerance (LPI) is inherited in an autosomal recessive pattern. Therefore, both copies of the altered gene (disease-causing change) must be present in the individual to have the disease. The affected child's parents carry one copy of the mutated gene and transfer it to the offspring.

What Are the Symptoms of Lysinuric Protein Intolerance?

Symptoms associated with lysinuric protein intolerance may differ based on body metabolism and outcomes. Symptoms of lysinuric protein intolerance can range from mild to severe.

The common symptoms involved are the following.

• Recurrent vomiting.

• Diarrhea.

• Abnormal bleeding.

• Lethargy.

• Intellectual disability.

• Feeding difficulties.

• Delayed maturation.

• Failure to thrive.

• Cognitive impairment.

• Anemia.

• Altered heart function.

• Decreased growth hormones.

• Thrombocytopenia.

• Respiratory insufficiency.

• Recurrent infections.

• Osteoporosis.

• Pathologic fracture.

• Leukopenia.

• Liver failure.

• Renal dysfunction.

• Cirrhosis.

• Complement deficiency.

• Decreased growth hormone.

• Decreased glomerular filtration.

• Infantile muscular hypotonia.

• Pancreatitis.

• Renal fibrosis.

• Tubulointerstitial nephritis.

• Hepatosplenomegaly.

• Hypercellularity of bone marrow.

• Coma.

How Can We Diagnose Lysinuric Protein Intolerance?

Diagnosis of lysinuric protein intolerance (LPI) is based on biochemical findings. Increased concentrations of the amino acids, lysine, arginine, and ornithine in urine can be identified and used as a primary diagnostic test. Other diagnostic aids that can be used for lysinuric protein intolerance are amino acid levels in plasma, urinary orotic acid concentration, serum ferritin levels, and lactate dehydrogenase isoenzyme levels. However, genetic screening can also rule out mutations of the SLC7A7 gene from DNA samples.

What Are the Treatment Options for Lysinuric Protein Intolerance?

Treatment of lysinuric protein intolerance involves the long-term restriction of a protein-rich diet and supplemental medications to manage other complications.

The standard treatment strategies used for lysinuric protein intolerance (LPI) are the following.

• Avoid a protein-rich diet.

• Oral supplemental nitrogen scavenger drugs such as Carnitine and L-lysine-hydrochloride.

• Use of citrulline to improve protein intolerance.

• Intravenous administration of nitrogen scavenger drugs like sodium phenylacetate, sodium benzoate, and arginine chloride reduces ammonia production.

• Vaccination against influenza and varicella zoster to reduce the risk of infections.

• Lung lavage in patients with pulmonary alveolar proteinosis to improve respiratory function.

Conclusion

Lysinuric protein intolerance (LPI) is a rare genetic metabolic disease caused due to the inability of body cells to absorb and use amino acids. It occurs due to a genetic mutation in the gene SLC7A7, which encodes for the protein involved in transporting amino acids arginine, lysine, and ornithine in the body cells. Mutation in the SCL7A7 gene disrupts the normal production and transport of these three amino acids leading to their shortage and associated effects. Lack of arginine and ornithine causes altered ammonia metabolism and results in elevated levels of ammonia in the blood and health effects. In addition, lysine deficiency causes disrupted bone maturation and bone defects. However, the treatment involves dietary regulation of protein-rich foods and medications to manage associated symptoms.