Hartnup Disease

Hartnup Disease

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Hartnup Disease is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • H Disease
  • Hart Syndrome
  • Pellagra-Cerebellar Ataxia-Renal Aminoaciduria Syndrome
  • Tryptophan Pyrrolase Deficiency
  • Hartnup Syndrome
  • Hartnup Disorder

Disorder Subdivisions

  • None

General Discussion

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.

Symptoms

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.

Causes

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.

Affected Populations

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.

Standard Therapies

Diagnosis

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.



Treatment

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.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

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.



JOURNAL ARTICLES

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.

Resources

CLIMB (Children Living with Inherited Metabolic Diseases)

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Crewe, CW2 6BG

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Tel: 4408452412173

Fax: 4408452412174

Email: enquiries@climb.org.uk

Internet: http://www.CLIMB.org.uk



March of Dimes Birth Defects Foundation

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White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

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TDD: (817)277-0553

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Internet: http://www.thearc.org



NIH/National Institute of Diabetes, Digestive & Kidney Diseases

Office of Communications & Public Liaison

Bldg 31, Rm 9A06

31 Center Drive, MSC 2560

Bethesda, MD 20892-2560

Tel: (301)496-3583

Email: NDDIC@info.niddk.nih.gov

Internet: http://www2.niddk.nih.gov/



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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