Hartnup, disease ... (hartnup disease) - Gen SLC6A19
Hartnup's's disease is a disorder caused by the body's inability to absorb certain amino acids in the diet. As a result, affected individuals are unable to metabolize these amino acids to produce other compounds such as vitamins and proteins. Most people with Hartnup's disease are able to get the vitamins and other necessary items from a well balanced diet. Although the only symptom of those affected with Hartnup's disease usually is the aminoaciduria, some affected individuals suffer episodes that show other signs, which may include rashes; cerebellar ataxia; and psychiatric symptoms such as depression or psychosis. These episodes are usually temporary and often are induced by other diseases, stress, poor diet, or fever. These signs and symptoms occur more often in childhood.
Hartnup disease is due to mutations in the SLC6A19 gene (solute carrier family 6 member 19), located on the short arm of chromosome 5 (5p15.33) encoding the synthesis of neutral amino acid transporter B0AT1. This conveyor B0AT1 is found mainly in the membrane of intestinal cells that make up the brush border cells of the intestinal mucosa ue absorb nutrients from food. B0AT1 transports neutral amino acids food to intestinal cells; From there, the amino acids are released into the bloodstream to be used by the body. B0AT1 also found in the membrane of kidney cells, specifically in the cells of the proximal tubules, helping to absorb nutrients and other materials in the blood and excrete substances that are not required in the urine. Kidney, B0AT1 neutral amino acids reabsorbed into the bloodstream so that they are not released into the urine.
They have been described at least 23 mutations in the gene responsible for the disease SLC6A19 Hartnup. Most of these mutations change specific amino acids in the protein B0AT1, reducing its activity. A mutation has been identified in several families affected aspartic acid replaces the amino acid by amino acid asparagine at position 173 in the protein (Asp173Asn or D173N). A reduction in activity B0AT1 causes removal of large amounts of neutral amino acids in the body. As a result, affected individuals have a deficiency of certain amino acids and vitamins. Most of those affected receive the nutrients they need from a balanced diet. However, some individuals have a nutrient deficiency due to poor diet, illness, stress, or a variety of other reasons, and may develop skin rashes or movement or psychiatric problems. It is believed that many of these features are related to a deficiency of vitamin B3 (niacin) and one of its main components, the amino acid tryptophan.
This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Hartnup disease by the complete PCR amplification of the exons of the SLC6A19 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).