Hyperlysinemia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Hyperlysinemia is an inherited condition that is characterized by elevated blood levels of lysine, which is one of the building blocks (amino acids) of proteins. Amino acids are not stored in the body and must be broken down when they are no longer needed. When the body's ability to break down lysine is impaired, lysine can build up and cause hyperlysinemia. Hyperlysinemia is classified as either type I or type II, depending on which steps of lysine breakdown are interrupted.

The signs and symptoms of hyperlysinemia can vary widely, even among members of the same family. The features that have been reported in people with hyperlysinemia have included short stature, speech and language delays, intellectual disabilities, behavioral abnormalities, abnormal muscle stiffness (spasticity), and seizures. However, some researchers have suggested that as many as half of all people with hyperlysinemia are asymptomatic, which means that they do not have any signs or symptoms of the disorder. These people may not even be aware that they have the condition.

Because the signs and symptoms of hyperlysinemia can vary and because hyperlysinemia is very rare, it is difficult for researchers to determine whether these features are caused by the condition itself or by other factors.

People with a condition called 2,4-dienoyl-CoA reductase (DECR) deficiency may also have hyperlysinemia. Additional features of DECR deficiency may include an inability to grow and gain weight as expected (faltering weight), developmental delays, abnormal brain function (encephalopathy), and eye abnormalities such as degeneration of the nerves that carry information from the eyes to the brain (optic atrophy).

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in the AASS gene cause both types of hyperlysinemia. The AASS gene provides instructions for making an enzyme called alpha-aminoadipic semialdehyde synthase. This enzyme performs two functions during the breakdown of lysine. First, the enzyme converts lysine to a molecule called saccharopine. This same enzyme also converts saccharopine to a molecule called alpha-aminoadipic semialdehyde.

The variants in the AASS gene that impair both the breakdown of lysine and the breakdown of saccharopine cause hyperlysinemia type I. The AASS gene variants that mostly impair the breakdown of saccharopine cause hyperlysinemia type II. Both type I and type II result in elevated levels of lysine in the blood. People with type II may also have elevated levels of saccharopine in the urine.

Researchers are not sure why some people with hyperlysinemia have signs and symptoms, while others are asymptomatic. It is also unclear how higher levels of lysine in the blood cause the signs and symptoms seen in some people with hyperlysinemia. More research is needed to fully understand the effects of hyperlysinemia on the body.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Hyperlysinemia is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. 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

The exact incidence of hyperlysinemia is unknown. Researchers have suggested that hyperlysinemia type I affects approximately 1 in 411,000 newborns. Hyperlysinemia type II is less common than type I.

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.

Abnormal CSF ornithine concentration · Frequent (79-30%)

Any deviation from the normal concentration of ornithine in the cerebrospinal fluid.

Abnormal enzyme/coenzyme activity · Frequent (79-30%)

Concentration or activity of an enzyme is above or below the limits of normal in the blood circulation.

Argininuria · Frequent (79-30%)

A increased concentration of arginine in the urine.

Atypical behavior · Frequent (79-30%)

Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.

Cystinuria · Frequent (79-30%)

An increased concentration of cystine in the urine.

Decreased CSF arginine concentration · Frequent (79-30%)

Abnormally decreased levels of arginine in cerebrospinal fluid.

Decreased urine alpha-ketoglutarate concentration · Frequent (79-30%)

A lower than normal concentration of 2-oxoglutaric acid in the urine.

Delayed speech and language development · Frequent (79-30%)

A degree of language development that is significantly below the norm for a child of a specified age.

Other findings in the same source

From: Orphanet

Additional reported features include EEG with spike-wave complexes (Frequent (79-30%)); Floppy infant (Frequent (79-30%)); Global developmental delay (Frequent (79-30%)); Hyperammonemia (Frequent (79-30%)); Hyperlysinemia (Frequent (79-30%)); Hyperlysinuria (Frequent (79-30%)); Hypoornithinemia (Frequent (79-30%)); Increased CSF lysine concentration (Frequent (79-30%)); Intellectual disability (Frequent (79-30%)); Microcephaly (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 Hyperlysinemia 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 Hyperlysinemia. 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.