Hartnup disease

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Hartnup disease is a condition caused by the body's inability to absorb certain protein building blocks (amino acids) from the diet. As a result, affected individuals are not able to use these amino acids to produce other substances, such as vitamins and proteins. Most people with Hartnup disease are able to get the vitamins and other substances they need with a well-balanced diet.

People with Hartnup disease have high levels of various amino acids in their urine (aminoaciduria). For most affected individuals, this is the only sign of the condition. However, some people with Hartnup disease have episodes during which they exhibit other signs, which can include skin rashes; difficulty coordinating movements (cerebellar ataxia); and psychiatric symptoms, such as depression or psychosis. These episodes are typically temporary and are often triggered by illness, stress, nutrient-poor diet, or fever. These features tend to go away once the trigger is remedied, although the aminoaciduria remains. In affected individuals, signs and symptoms most commonly occur in childhood.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Hartnup disease is caused by mutations in the SLC6A19 gene. This gene provides instructions for making a protein called B0AT1, which is primarily found embedded in the membrane of intestine and kidney cells. The function of this protein is to transport certain amino acids into cells. In the intestines, amino acids from food are transported into intestinal cells then released into the bloodstream so the body can use them. In the kidneys, amino acids are reabsorbed into the bloodstream instead of being removed from the body in urine. In the body, these amino acids are used in the production of many other substances, including vitamins and proteins. One particular amino acid transported by B0AT1, tryptophan, is needed to produce vitamin B3 (also known as niacin).

SLC6A19 gene mutations result in the production of a B0AT1 protein with reduced activity. As a result, specific amino acids cannot be taken in by cells and are instead removed from the body as waste. Because these amino acids are removed from the body without being used, people with this condition may be lacking (deficient) in certain amino acids and vitamins. However, individuals who are nutrient-deficient due to their diet, illness, stress, or a variety of other reasons, can develop serious signs and symptoms of this condition including rashes, cerebellar ataxia, and psychiatric symptoms. Researchers believe that many of these features are related to a deficiency of tryptophan and niacin, specifically.

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 mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Hartnup disease is estimated to affect 1 in 30,000 individuals.

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 urinary color · Very frequent (99-80%)

An abnormal color of the urine, that is, the color of the urine appears different from the usual straw-yellow color.

Anxiety · Very frequent (99-80%)

Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.

Ataxia · Very frequent (99-80%)

Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).

Cutaneous photosensitivity · Very frequent (99-80%)

An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.

EEG abnormality · Very frequent (99-80%)

Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.

Emotional lability · Very frequent (99-80%)

Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances.

Hallucinations · Very frequent (99-80%)

Perceptions in a conscious and awake state that, in the absence of external stimuli, have qualities of real perception. These perceptions are vivid, substantial, and located in external objective space.

Hyperreflexia · Very frequent (99-80%)

Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.

Other findings in the same source

From: Orphanet

Additional reported features include Hypotonia (Very frequent (99-80%)); Migraine (Very frequent (99-80%)); Neutral hyperaminoaciduria (Very frequent (99-80%)); Abnormality of vision (Frequent (79-30%)); Elevated urinary indican level (Frequent (79-30%)); Malabsorption (Frequent (79-30%)); Nystagmus (Frequent (79-30%)); Photophobia (Frequent (79-30%)); Skin rash (Frequent (79-30%)); Strabismus (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 Hartnup disease 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 Hartnup disease. 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.