Lysinuric protein intolerance

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Lysinuric protein intolerance is a disorder caused by the body's inability to digest and use certain protein building blocks (amino acids), namely lysine, arginine, and ornithine. Because the body cannot absorb these amino acids, which are found in many protein-rich foods, nausea and vomiting are typically experienced after ingesting protein.

People with lysinuric protein intolerance have a variety of features, such as an enlarged liver and spleen (hepatosplenomegaly), short stature, muscle weakness, impaired immune function, and brittle bones that are prone to fracture (osteoporosis). A lung disorder called pulmonary alveolar proteinosis may also develop. This disorder is characterized by protein deposits in the lungs, which interfere with lung function and can be life-threatening. An accumulation of amino acids in the kidneys can cause end-stage renal disease (ESRD), in which the kidneys become unable to filter fluids and waste products from the body effectively. A lack of certain amino acids can cause elevated levels of ammonia in the blood. If ammonia levels are too high for too long, they can cause coma and intellectual disability.

The signs and symptoms of lysinuric protein intolerance typically appear after infants are weaned and receive greater amounts of protein from solid foods.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in the SLC7A7 gene cause lysinuric protein intolerance. The SLC7A7 gene provides instructions for producing a protein called y+L amino acid transporter 1 (y+LAT-1), which is involved in transporting lysine, arginine, and ornithine between cells in the body. The transportation of amino acids from the small intestine and kidneys to the rest of the body is necessary for the body to be able to make and use proteins.

Variants in the y+LAT-1 protein disrupt the transportation of lysine, arginine, and ornithine. As a result, these amino acids are not absorbed by cells in the small intestine, leading to a shortage of lysine, arginine, and ornithine in the body. In the kidneys, the amino acids cannot be returned to the bloodstream (a process called reabsorption) but are instead removed from the body in urine.

This shortage of lysine, arginine, and ornithine disrupts many vital functions. Arginine and ornithine are involved in a cellular process called the urea cycle, which processes the excess nitrogen (in the form of ammonia) that is generated when protein is used by the body. The lack of arginine and ornithine in the urea cycle causes elevated levels of ammonia in the blood (hyperammonemia). Lysine is particularly abundant in collagen molecules, which give structure and strength to connective tissues such as skin, tendons, and ligaments. A deficiency of lysine may contribute to the short stature and osteoporosis seen in people with lysinuric protein intolerance. However, the cause for most of the features of lysinuric protein intolerance is unclear.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have variants. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Lysinuric protein intolerance is estimated to occur in 1 in 50,000 newborns in Finland. This condition has also been found in numerous individuals in Japan and Italy. Outside these populations, this condition occurs less frequently, but the exact incidence is unknown.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Failure to thrive · Very frequent (99-80%)

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

Abnormal bleeding · Frequent (79-30%)

An abnormal susceptibility to bleeding, often referred to as a bleeding diathesis. A bleeding diathesis may be related to vascular, platelet and coagulation defects.

Abnormal pulmonary interstitial morphology · Frequent (79-30%)

Abnormality of the lung parenchyma extending to the pulmonary interstitium and leading to diffuse pulmonary fibrosis.

Abnormal renal tubule morphology · Frequent (79-30%)

An abnormality of the renal tubules.

Abnormality of serine metabolism · Frequent (79-30%)

Any deviation from the normal concentration of serine in the blood circulation.

Anemia · Frequent (79-30%)

A reduction in erythrocytes volume or hemoglobin concentration.

Argininuria · Frequent (79-30%)

A increased concentration of arginine in the urine.

Bone marrow hypercellularity · Frequent (79-30%)

A larger than normal amount or percentage of hematopoietic cells relative to marrow fat.

Other findings in the same source

From: Orphanet

Additional reported features include Chronic kidney disease (Frequent (79-30%)); Cirrhosis (Frequent (79-30%)); Cognitive impairment (Frequent (79-30%)); Decreased HDL cholesterol concentration (Frequent (79-30%)); Decreased glomerular filtration rate (Frequent (79-30%)); Delayed skeletal maturation (Frequent (79-30%)); Diarrhea (Frequent (79-30%)); Elevated circulating hepatic transaminase concentration (Frequent (79-30%)); Elevated plasma citrulline (Frequent (79-30%)); Feeding difficulties (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Lysinuric protein intolerance is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Lysinuric protein intolerance. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.