What else is it called?
- Hartnup disorder
- Hartnup’s disease
- Neutral amino acid transport defect
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What causes it?
Hartnup disease is a rare inherited metabolic disorder caused a defect in the SLC6A19 gene. The gene provides instructions to the BOAT1 protein. This protein is found in the cells in your kidneys and intestines. It is needed to transport specific amino acids into cells so your body can absorb them and use them to produce other substances such as proteins and vitamins. One of the amino acids that BOAT1 transports is called tryptophan which your body uses to produce vitamin B3 (niacin)
This means that if you have Hartnup disease, your body removes specific amino acids as a waste product rather than absorbing them. Therefore your body is not able to use the amino acids to produce the vitamins and proteins needed. Most people with Hartnup disease can still get these through a balanced diet but others may have a deficiency (a lack) of those amino acids which could not be absorbed and the vitamins and minerals they would normally help to produce. For these people, severe symptoms can present with the cause thought likely to be tryptophan and niacin deficiencies.
How common is it?
Hartnup disease is estimated to affect 1 in 30,000 individuals. However, a more recent study (2019) suggests this may be closer to 1 in 15,000.
What are the signs and symptoms?
Symptoms vary from case to case. For most people with Hartnup disease, the only symptom is high levels of amino acids in the urine (amino aciduria).
For others, symptoms appear in acute episodes which may be triggered by the following:
- Exposure to sunlight
- Certain medications
- Poor diet
- Low protein or vegan diets
- Hot weather
Symptoms most commonly occur in childhood with the first episode starting typically between the ages of three and nine years of age, although they can occur as early as 10 days of age. The frequency of episodes generally reduces with age. Diarrhoea may occur before or after an episode occurs. Episodes generally progress over several days, lasting for 1-4 weeks before spontaneously improving.
Rarely, the first episode may occur in early adulthood. In these cases, seizures have commonly been reported as being the first symptom. Heartburn may also be a symptom in adulthood.
Symptoms of these episodes may include distinctive skin rashes which are be described as red, scaly, and sensitive to light. They occur on the face, arms, hands, and other exposed areas of skin.
In some cases there may be neurological symptoms which similarly occur in episodes with a rapid onset, these include:
- Difficulty coordinating movements (ataxia)
- Speech difficulties
- Tremor of the hands and tongue
- High muscle tone and tightness of the muscles leading to rigid movements
- Sight problems
- Emotional instability
Additional symptoms include:
- Delays in reaching growth milestones
- Short stature
- Low muscle tone (hypotonia)
- Double vision (diplopia)
- Involuntary eye movements (nystagmus)
- Drooping of the eyelids (ptosis)
- Eye discomfort in bright light
- Misalignment of the eyes; the eyes point in different directions particularly when focusing on an object (strabismus)
Other associated symptoms have been described but there is some uncertainty about whether they are linked directly with Hartnup disease or are incidental.
- Cognitive delays
- Mild learning difficulties
Symptoms usually go away after the trigger has been removed; i.e. fever has dropped or following recovery from illness. However, high levels of amino acid in the urine still remains.
How is it diagnosed?
Diagnosis can only be made via specialised analysis of the urine. Genetic testing may, in some cases, be used to confirm diagnosis. In the US, often people may only discover they have the condition through routine screening.
Can it be treated?
Those who do not have symptoms often do not require treatment.
The main treatment is maintaining a well-controlled and balanced diet which is high in protein and avoiding triggers which can precipitate an episode. This includes avoiding direct sunlight and wearing sunblock or protective clothes. Medications that should be avoided include sulfonamides, nonsteroidal anti-inflammatory drugs (NSAIDs), tetracyclines, and oral contraceptives which increase sensitivity to light (cause photosensitivity).
Dietary supplements of nicotinamide or niacin can be beneficial in the prevention of episodes. In some cases, nicotinamide may be recommended for use during an acute episode to improve skin rashes and neurological symptoms. Those with severe neurological involvement may require neurologic and psychiatric treatment.
Some reports suggest that L-tryptophan ethyl ester may be a beneficial treatment which improves symptoms by restoring tryptophan levels in the serum and fluid surrounding the brain and spinal cord (cerebrospinal fluid).
All other treatment is based on managing individual symptoms and providing support and care for the individual.
With adequate diet most cases will remain asymptomatic (not show any symptoms). With good management, the prognosis is good and life expectancy normal.
Do my family need to be tested?
Humans have chromosomes composed of DNA. Genes are pieces of DNA that carry the genetic instruction. Each chromosome may have several thousand genes.
The word mutation means a change or error in the genetic instruction. We inherit particular chromosomes from the egg of the mother and sperm of the father.
The genes on those chromosomes carry the instruction that determines characteristics, which are a combination of the parents. Hartnup disease is an inherited condition. There is nothing that could have been done to prevent your baby from having Hartnup disease.
Everyone has a pair of genes that code for the BOAT1 protein. In children with Hartnup disease, neither of these genes works correctly. These children inherit one non-working Hartnup disease gene from each parent.
Parents of children with Hartnup disease are carriers of the condition. Carriers do not have Hartnup disease because the other gene of this pair is working correctly.
When both parents are carriers, in each pregnancy the risk to the baby is as follows:
- 25% chance (1 in 4) of developing Hartnup disease
- 50% chance (1 in 2) for the baby to be a carrier
- 25% chance (1 in 4) for the baby to have two working genes and neither have the disorder nor be a carrier