Hartnup disease is a rare metabolic disorder inherited as an autosomal recessive trait. It involves an inborn error of amino acid metabolism as well as niacin deficiency. Factors that may precipitate acute attacks of this disorder may include poor nutrition, exposure to sunlight, sulphonamide medications and/or psychological stress. Hartnup disease may be marked by skin problems, coordination impairment, vision problems, mild mental retardation, gastrointestinal problems, and central nervous system abnormalities. Frequency of attacks usually diminishes with age.
The symptoms of Hartnup disease vary from case to case. Many individuals do not have any apparent symptoms (asymptomatic). When symptoms occur the most common are red, scaly light-sensitive (photosensitive) rashes on the face, arms, extremities, and other exposed areas of skin. Other symptoms include sudden attacks of impaired muscle coordination (ataxia), unsteady walk (gait), impaired articulation of speech (dysarthia), spasticity, and occasional tremors of the hands and tongue. Some affected individuals may also experience double vision (diplopia), involuntary rhythmic movements of the eyes (nystagmus), droopy upper eyelids (ptosis), and/or dizziness (vertigo). Abnormally high levels of amino acids may be present in urine (aminoaciduria). Diarrhea and fainting may occur with this disorder.
Mental retardation has been seen in some cases of Hartnup disease. Short stature, emotional instability, seizures, and a reduction of intellectual abilities (dementia) may also be symptomatic of untreated Hartnup disease. In addition, some affected individuals may experience depression, delusions, and/or hallucinations. Mild heart irregularities (arrhythmias) may also occur but are extremely rare.
Hartnup disease is inherited as an autosomal recessive trait. It is an inborn error of amino acid metabolism including tryptophan, and the decomposition of these amino acids in the intestines. Precipitating factors that may cause acute attacks may include poor nutrition, fever, exposure to sunlight, sulphonamide medications and/or psychological stress.
Genetic diseases are determined by two genes, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.
A defective gene responsible for Hartnup disease is believed to be located on the long arm of chromosome 11 (11q13). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11q13” refers to band 13 on the long arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Researchers have determined that a gene responsible for some cases of Hartnup disease is located on the short arm of chromosome 5 (5p15.33). The gene is known as the SLC6A19 gene and encodes sodium-dependent amino acid transport.
Hartnup disease affects both males and females in equal numbers. It usually begins in childhood and continues into adulthood. The number of people affected by Hartnup disease is unknown. It has been estimated to affect between one in 14,500 and one in 100,000 live births worldwide.
The diagnosis of Hartnup disease may be confirmed by urine analysis performed during routine screening at birth that detects a unique pattern of amino acids in the urine.
Genetic studies on children born to mothers affected by Hartnup disease suggest that the abnormal metabolism of amino acids in this disorder does not seem to have an adverse effect on the embryo.
Attacks of Hartnup disease in people affected by this disorder can be reduced or avoided by maintaining good nutrition, supplementing the diet with nicotinamide or niacin, and avoiding the sun and sulphonamide drugs. Other treatment is symptomatic and supportive. Genetic counseling may be helpful for affected families.
The drug L-tryptophan ethyl ester may be used to treat Hartnup disease.
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Buist NRM, Winter SC. Hartnup Disease. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:458.
Fauci AS, et al., eds. Harrison’s Principles of Internal Medicine, 14th Ed. New York, NY: McGraw-Hill, Inc; 1998:2206.
Adams, RD, et al., eds. Principles of Neurology. 6th ed. New York, NY: McGraw-Hill, Companies; 1997:953.
Behrman RE, ed. Nelson Textbook of Pediatrics, 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996:1099, 1863.
Menkes JH, au., Pine JW, et al., eds. Textbook of Child Neurology, 5th ed. Baltimore, MD: Williams & Wilkins; 1995:59-60.
Scriver CR, et al., eds. The Metabolic and Molecular Basis of Inherited Disease. 7th Ed. New York, NY; McGraw-Hill Companies, Inc; 1995:3629-42.
Yamada T, et al., eds. Textbook of Gastroenterology. 2nd ed. Philadelphia, PA: J.B. Lippincott Company; 1995:464-5.
Champion RH, et al., eds. Textbook of Dermatology. 5th ed. Cambridge, MA: Blackwell Scientific Publications; 1992:2355-6.
Brenner BM, et al., eds. The Kidney, 4th ed. Philadelphia, PA: W. B. Saunders Company; 1991:1601-2.
Buyce ML, ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990:836-7.
Seow HF, et al. Hartnup disease is caused by mutations in the gene encoding the natural amino acid transporter SLC6A19. Nat Genet. Epub 2004; Aug 1.
Kleta R, et al. Mutations in SLC6A19, encoding B(0)AT1, cause Hartnup disorder. Nat Genet. Epub 2004; Aug 1.
Mahon BE, et al. Maternal Hartnup disorder. Am J Med Genet. 1986;24:513-8.
Shih VE, et al. Occurrences of methylmalonic aciduria and hartnup disorder in the same family. Clin Genet. 1984;26:216-20.
Tahmoush AJ, et al. Hartnup disease. Clinical, pathological, and biochemical observations. Arch Neurol. 1976;33:797-807.
FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:234500; Last Update:3/17/2004. Available at: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=234500 Accessed on: August 10, 2004.
Karadaglic D. Hartnup Disorder. Emedicine. 2003. Available at: http://www.emedicine.com/derm/topic713.htm Accessed on: August 10, 2004.
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