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Alternative Names
Pellagra-like dermatosis, Hartnup Syndrome, Hartnup disorder, Tryptophan Pyrrolase Deficiency | |
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Causes
Hartnup disease is inherited (present at birth) as an autosomal recessive trait, meaning that a child must inherit two copies of the defective gene, one from each parent in order to be affected by the disorder. The gene responsible for the disease is SLC6A19, located on chromosome 5.
The symptoms usually start in childhood, between 3-9 years of age.
Symptoms of the disease occur because of defective amino acid transport proteins in the walls of intestines and renal tubules that transport amino acids across intestinal and renal tubular cells. Due to these defective transport proteins, tryptophan (an essential amino acid) and other neutral amino acids are not absorbed in the small intestine and are converted by bacteria in the intestinal lumen to indolic compounds that are toxic to the brain. Also, there is decreased absorption of amino acids in the kidneys resulting in aminoaciduria. Deficiency of tryptophan leads to niacin deficiency (tryptophan is converted in the liver to niacin), which is responsible for most of the symptoms. | |
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Definition of Disease
Hartnup disease is a rare inherited disorder that decreases the absorption of certain amino acids (especially tryptophan) in the small intestine and kidneys. It is characterized primarily by aminoaciduria (excess amount of amino acids excretion in urine), cerebellar ataxia (muscular incoordination), and a pellagra-like rash. | |
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Classification
No further subtypes of the disease. | |
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Signs and Symptoms
Most patients with the disease do not have any symptoms. Symptoms may be precipitated by exposure to sunlight, fever, poor nutrition, drugs (sulphonamides), emotional or physical stress. Symptoms most commonly involve the skin and brain and include:
- Skin sensitivity to light (photosensitivity).
- The skin becomes dry, red and scaly on exposure to sunlight (Pellegra-like Rash).
- Skin changes leave long-lasting patches of very light (hypopigmented) or very dark (hyperpigmented) areas.
- Muscle weakness
- Unsteady gait or Uncoordinated movements (cerebellar ataxia)
- Vision problems include double vision, nystagmus, photophobia, and strabismus.
- Diarrhea
- Short stature
- Headache
- Collapsing or fainting
- Gingivitis, stomatitis, and glossitis suggest niacin deficiency.
- Psychiatric symptoms such as anxiety, emotional instability, mood swings, fear and even psychoses may also be seen.
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Diagnosis of Hartnup Diseases
- Urine Chromatography: High levels of neutral amino acids (up to 5-10 times normal) and normal levels of other amino acids are diagnostic of the disorder.
- Jejunal Biopsy - transport defect may be identified in vitro.
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Representative Case Study
A 7 year old girl belonging to a poor family presented with complaint of skin eruptions, ataxia, diarrhea and mental changes, suggestive of niacin deficiency. On examination the patient had areas of hypopigmentation and hyperpigmentation on the skin. Urine examination showed neutral aminoaciduria which indicated Hartnup disease. | |
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Treatment of Hartnup Disease
- High-protein diet.
- Protection from sunlight by wearing protective clothing, sunglasses, and sunscreen.
- If skin symptoms appear, consult a dermatologist (skin specialist).
- Nicotinic acid or nicotinamide supplements daily.
- Psychiatric treatment, if mood swings or psychiatric problems.
Spontaneous remission normally occurs in 1-4 weeks. | |
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Prevention
In individuals with family history of hartnup disease, go for genetic counseling if planning for pregnancy. | |
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Complications Of Hartnup Disease
- Mild mental retardation
- Changes in skin pigment that are permanent
- Psychiatric problems
- Rarely, severe CNS involvement may lead to death.
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Prognosis of Hurtnup Disease
Most of the people with this disorder can lead a normal life with no disability; even in patients with symptoms it may rarely result in death. Frequency of attacks usually decreases with age. | |
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