Hartnup disease is caused due to the mutation of the gene SLC6A19

How often do we stress about having a balanced diet on regular basis?  Well, it turns out that it does have much more important than we have ever thought. We are being advised on having a proper amount of protein, carbs, fats, vitamins, etc. A proper diet with high protein can certainly avert disorders like hartnup disease caused due to mutated genes.

  • Hartnup disease is also popularly known as pellagra like disease and aminoaciduria.

The disease is uncommon as its name sounds. It is estimated that hartnup disease affects 1 in 30,000 individuals. Since it is an autosomal recessive disorder, the parents of an individual must carry one copy of the mutated gene. They typically do not show any symptoms of the condition. So let’s find out what are the causes of such rare disease and how it can be prevented.

 CAUSES OF HARTNUP DISEASE

Hartnup disease is caused due to the mutation of the gene SLC6A19 which is found on chromosome 5. This gene is responsible for the making of protein B0AT1 which is primarily found embedded in the membrane of intestine and kidney cells. The function of the protein is to transport certain amino acids into the cells. In the intestines, amino acids from food are transported into the intestinal cells then released into the bloodstream so the body can use them. In kidneys, amino acids are absorbed into the bloodstream rather than being removed from the body through urine. In the body, these amino acids are used in the production of many other proteins and vitamins. One particular amino acid transported by B0AT1, tryptophan is needed to produce Vitamin B3 (Niacin).

EFFECTS OF HARTNUP DISEASE

Tryptophan is essential for the production of serotonin, melatonin and niacin. Due to the mutation in the gene SLC6A19, the production of the protein B0AT1 decreases. As a result, the body can not absorb these amino acids and these are being removed without being used. This LACKING(DEFICIENT) caused in people with poor diet, illness, stress or any other symptoms or signs can lead to conditions of cerebral ataxia, erythematous skin rashes, and psychiatric symptoms. The symptoms are triggered by fever, drugs, or during situations when an affected person is under emotional or physical stress as during such illness.

SIGNS AND SYMPTOMS

The symptoms of this disease are usually asymptomatic. The symptoms are first seen in a person between the age of 3-9. It’s on the rarest occasion that it appears on an adult. The most common symptoms are red, scaly light-sensitive (photosensitive) rashes on the face, arms, extremities, and other exposed areas of the skin.

A wide variety of neurological abnormalities can be seen which includes sudden episodes of impaired muscle coordination also called ataxia, an unsteady walk (gait), impaired articulation of speech (dysarthria), occasional tremors of hands and tongue, and spasticity, a condition marked by increased muscle tone and stiffness of muscle, particularly those of legs.

There have also been some reports of delayed cognitive development and, in rare instances, mild intellectual disability in some children. It is, however, unclear whether these symptoms are related to hartnup disease or incidentally occurred in the same individual and were therefore attributed to hartnup disorder. Similarly, seizures, fainting, trembling, lack of muscle tone (hypotonia), headaches, fever, dizziness and/or vertigo, and delays in motor improvement have been observed but may be unrelated. Some affected individuals may experience rapid mood changes, depression, anxiety, delusions and/ or hallucinations.

Some children might also face

  1. Short stature
  2. Double  vision (diplopia)
  3. Involuntary eye movements (nystagmus)
  4. Droopy upper eyelids(ptosis)
  5. Diarrhoea

DIAGNOSIS

Due to the wide spectrum of its symptoms an unambiguous diagnosis can be only made through urine analysis. Paediatricians can request this analysis to be done by any pathology lab. This test uses chromatography and mass spectroscopy to detect elevated levels of amino acids in the urine. Mainly basic amino acids are detected. Molecular genetic testing can confirm Hartnup disorder. It involves the detection of the alternations in the gene SLC19A6.

TREATMENT

Individuals who are affected by the disease but does not show any symptoms will not require any treatment. A low protein diet may trigger symptomatic episodes which can be reduced or avoided by maintaining a good nutrition diet and avoiding sun exposure. One should also avoid certain dugs like sulphonamide. Supplementing the diet with nicotinamide or niacin is also of benefit.

CONCLUSION

Keeping in mind all the above points, if one is affected with hartnup disease usually the symptoms will appear in childhood. The symptoms should not be neglected. Care must be taken with the patient. And the patient must get a regular checkup done.

1 Comment

  1. Anthony Claire

    Some good stuff you’ve written there.

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