Hartnup Disease - A Genetic Disorder

Introduction

Proteins are the building blocks of the human body. Proteins are made up of amino acids, which include acidic, essential, and neutral amino acids. Decreased absorption of neutral types of amino acids in the gut and kidney leads to the nutritional disorder called Hartnup disease. The etiology of Hartnup disease is genetic. The missense, frameshift, splice site, and nonsense mutations of the SLC6A19 gene cause Hartnup disease. Hartnup disease has various clinical features, and specific triggers aggravate the symptoms. Some preventive measures are taken to avoid the triggers of Hartnup disease.

What Is Hartnup Disease?

Hartnup disease was first described in 1956 by Boren et al., and it was first presented in a boy from the Hartnup family. Hartnup disease is an autosomal recessive genetic disorder characterized due to the decreased absorption of neutral amino acids in the gut and kidney. Hartnup disease is mainly caused by the mutation of the SLC6A19 gene, which encodes the B0AT1, protein transport in the gut and kidney. Hartnup disease has no age or gender preferences. Various skin conditions arise due to the deficiency of neutral amino acids like niacin. Hartnup disease occurs with an early onset, and specific triggers aggravate the clinical symptoms. The triggers of Hartnup disease are given below.

• Increased sunlight.

• Hot weather, like summer.

• Nutrition deficiency.

What Causes Hartnup Disease?

Hartnup disease is an autosomal recessive disorder caused due to the missense, frameshift, splice site, or nonsense mutations of the SLC6A19 gene. Mutation of the SLC6A19 gene affects the activation of B0AT1, causing malabsorption of the neutral amino acid in the gut and kidney. The pathophysiology of Hartnup disease is mentioned below.

• Mutation of SLC6A19.

• Defect in B0AT1 protein.

• Increased excretion of neutral amino acids via urine and feces.

• Colonic bacteria convert the excessive tryptophan into indoles.

• Conjugation of indolic components forms indican.

• Indican is excreted in the urine.

• The precursor of niacin is tryptophan, and tryptophan deficiency causes niacin deficiency.

• Niacin deficiency causes pellagra.

• Skin lesions and some other neurological problems arise in Hartnup disease.

What Are the Symptoms of Hartnup Disease?

Hartnup disease has several symptoms, which include skin eruptions and neurological disorders. In addition, some of the triggers will aggravate the symptoms. Some of the symptoms of Hartnup disease are mentioned below.

Skin problems during Hartnup disease are given below.

• Pellagra.

• Skin is red or erythematous.

• Sun-exposed areas show scaly patches.

• Skin rashes present.

Neurological symptoms of Hartnup disease are given below.

1. Tremors.

2. Mood disorders.

3. Depression.

4. Anxiety.

5. Ataxia.

6. Convulsions.

7. Hallucinations.

8. Psychosis.

9. Disorientation.

Other symptoms include short stature and a slight delay in developmental milestones.

How Is Hartnup Disease Diagnosed?

The diagnosis of Hartnup disease is made by urine analysis. Excessive neutral amino acids are excreted via urine in Hartnup conditions. Therefore, urine analysis is done to evaluate neutral aminoaciduria. Proline, an amino acid, is absent in urine. The diagnosis of Hartnup disease is given below.

1. Family history of the patient.

2. Physical examination.

3. Urine analysis.

4. Paper chromatography of urine which includes the evaluation of neutral amino acids.

5. The neutral amino acids to be evaluated in urine in diagnoses of Hartnup disease are given below.

• Valine.

• Serine.

• Phenylalanine.

• Histidine.

• Glutamine.

• Leucine.

• Asparagine.

• Citrulline.

• Isoleucine.

• Threonine.

• Alanine.

• Tyrosine.

• Tryptophan.

• Indican, a by-product of degraded tryptophan, is excreted in the urine.

What Is the Differential Diagnosis of Hartnup Disease?

The signs and symptoms of Hartnup disease are early in onset and show similar symptoms to other conditions. Therefore, comparison of symptoms will help in differential diagnosis and avoid misdiagnosis. Some of the differential diagnoses of Hartnup disease are given below.

• Pellagra.

• Systemic lupus erythematosus.

• Congenital poikiloderma.

• Seborrheic dermatitis or seborrheic eczema.

• Carcinoid syndrome.

What Are the Complications of Hartnup Disease?

Sometimes, Hartnup disease causes many complications. Some of the complications of Hartnup disease are given below:

• Skin hyperpigmentation.

• Skin xerosis.

• Retardation of growth.

• Poor academic performance.

• Severe neurodegenerative problems.

• Seizures.

• Delirium.

• Psychosis.

What Is the Treatment of Hartnup Disease?

The treatment of Hartnup disease is done by providing nutritional supplements and neurological workups in severe neurodegenerative conditions. Aggravated symptoms are avoided by avoiding the triggers. The different modes of treatment done for treating Hartnup disease are given below.

• Avoiding the triggers.

• High protein diet.

• Nicotinamide supplements.

• Neurologic workup.

• Psychiatric treatment.

• Neurological treatment.

• Well-balanced diet.

How to Prevent Hartnup Disease?

Some preventive measures can be followed to avoid the aggravation of symptoms. Patient education is mandatory about preventative measures. The preventive measure for Hartnup disease is given below.

• Avoiding excess sunlight exposure.

• Wearing sun-protective clothes.

• Application of sunscreen products containing sun protection factor (SPF) during outdoor activities.

• The photosensitive rash is avoided by avoiding drugs like sulfonamides, NSAIDs (nonsteroidal anti-inflammatory drugs), and tetracyclines.

• Oral contraceptives can also be avoided.

What Is the Recommended Diet for Hartnup Disease?

Niacin deficiency occurs in Hartnup disease. The clinical symptoms are resolved with a proper protein-rich, stable diet. Niacin, also called vitamin B3, is present in various foods. Therefore, some protein-rich and niacin-rich foods are taken to reduce the symptoms of Hartnup disease. Some of the food tips for Hartnup disease are given below.

• Red meat like beef, liver of beef, and pork meat.

• Poultry.

• Chicken liver is the best source of niacin.

• Chicken breast is a source of niacin and lean protein.

• Tuna fish are high in vitamins B3, B6, omega-three fatty acids, and protein.

• Turkey contains tryptophan.

• Salmon is a good niacin source.

• Anchovies.

• Pork meat includes tenderloin and pork chops.

• Ground beef.

• Peanuts.

• Avocado.

• Bananas.

• Brown rice.

• Whole wheat.

• Mushrooms.

• Green peas.

• Potatoes.

• White bread.

• Pasta.

• Fortified foods.

Conclusion

Hartnup disease is an autosomal recessive genetic disorder; decreased absorption of neutral amino acids results in the gut and kidney causing excessive excretion of neutral aminoaciduria. Excessive loss of tryptophan causes niacin deficiency. The pellagra-like skin symptoms and neurological symptoms occur due to niacin deficiency. Diagnosis of Hartnup disease is made by urine analysis, and treatment is done to avoid the triggers and complications. Preventive measures are followed, and proper awareness and patient education about the preventive measures are done to prevent the risk of Hartnup disease. However, the recurrence and the symptoms of Hartnup disease will be resolved with niacin supplements, and the prognosis of Hartnup disease is good.