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| {{Infobox medical condition | | | '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' |
| Name = Hartnup disease | | | {{Infobox_Disease | |
| Image = L-tryptophan-skeletal.png | | | Name = Iodine deficiency | |
| Caption = [[Tryptophan]] | | | Image = | |
| DiseasesDB = 5638 | | | Caption = | |
| ICD10 = {{ICD10|E|72|0|e|70}} | | | DiseasesDB = 6933 | |
| ICD9 = {{ICD9|270.0}} | | | ICD10 = {{ICD10|E|00||e|00}} - {{ICD10|E|02||e|00}} | |
| | ICD9 = | |
| ICDO = | | | ICDO = | |
| OMIM = 234500 | | | OMIM = | |
| MedlinePlus = 001201 | | | MedlinePlus = | |
| eMedicineSubj = derm | | | eMedicineSubj = | |
| eMedicineTopic = 713 | | | eMedicineTopic = | |
| MeshID = D006250 | | | MeshID = | |
| }} | | }} |
| [[Image:autorecessive.svg|thumb|right|Hartnup disease has an autosomal recessive pattern of [[inheritance]].]]
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| '''Hartnup disease''' (also known as "[[pellagra]]-like [[dermatosis]]"<ref name="Bolognia">{{cite book |author=Rapini, Ronald P. |author2=Bolognia, Jean L. |author3=Jorizzo, Joseph L. |title=Dermatology: 2-Volume Set |publisher=Mosby |location=St. Louis |year=2007 |pages= |isbn=1-4160-2999-0 |oclc= |doi= |accessdate=}}</ref> and "Hartnup disorder"<ref>{{OMIM|234500}}</ref>) is an [[autosomal]] [[recessive]]<ref name="pmid15286787">{{cite journal |pmid=15286787 |date=September 2004 |vauthors=Kleta R, Romeo E, Ristic Z, Ohura T, Stuart C, Arcos-Burgos M, Dave MH, Wagner CA, Camargo SR, Inoue S, Matsuura N, Helip-Wooley A, Bockenhauer D, Warth R, Bernardini I, Visser G, Eggermann T, Lee P, Chairoungdua A, Jutabha P, Babu E, Nilwarangkoon S, Anzai N, Kanai Y, Verrey F, Gahl WA, Koizumi A |title=Mutations in SLC6A19, encoding B0AT1, cause Hartnup disorder |volume=36 |issue=9 |pages=999–1002 |doi=10.1038/ng1405 |journal=Nature Genetics}}</ref> [[metabolic disorder]] affecting the absorption of nonpolar [[amino acids]] (particularly [[tryptophan]] that can be, in turn, converted into [[serotonin]], [[melatonin]], and [[niacin]]). Niacin is a precursor to [[nicotinamide]], a necessary component of [[NAD+]].<ref name="Andrews">{{cite book |author=James, William D. |author2=Berger, Timothy G.|title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |location= |year=2006 |pages= |isbn=0-7216-2921-0 |oclc= |doi= |accessdate=|display-authors=etal}}</ref>{{rp|541}}
| | ==Overview== |
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| The causative gene, ''[[SLC6A19]]'', is located on [[chromosome 5]].<ref name="pmid15286788">{{cite journal |pmid=15286788 |doi=10.1038/ng1406 |date=September 2004 |vauthors=Seow HF, Brer S, Brer A, Bailey CG, Potter SJ, Cavanaugh JA, Rasko JE |title=Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19 |volume=36 |issue=9 |pages=1003–7 |journal=Nature Genetics}}</ref>
| | [[Iodine]] is an essential [[trace element]]; the [[thyroid hormone]]s [[thyroxine]] and [[triiodotyronine]] contain iodine. In areas where there is little iodine in the diet—typically remote inland |
| | areas where no marine foods are eaten—'''iodine deficiency''' gives rise to |
| | [[goiter]] (so-called [[endemic goitre]]), as well as [[cretinism]], which results in developmental delays and other health problems |
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| ==Signs and symptoms== | | In some such areas, this is now combatted by the addition of small amounts of iodine to table salt in form of [[sodium iodide]], [[potassium iodide]], [[potassium iodate]]—this product is known as ''iodized salt''. Iodine compounds have also been added to other foodstuffs, such as flour, in areas of deficiency. |
| Hartnup disease manifests during infancy with variable clinical presentation: failure to thrive, photosensitivity, intermittent ataxia, [[nystagmus]], and tremor.
| | ==Pathophysiology== |
| | ===Goitre=== |
| | {{main|Goitre}} |
| | Low amounts of [[thyroid hormone]]s in the blood, due to lack of [[iodine]] to make them, give rise to high levels of the [[pituitary hormone]] [[TSH]], which in turn stimulate abnormal growth of the [[thyroid gland]], sometimes causing [[goitre]]s. |
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| Nicotinamide is necessary for [[neutral amino acid transporter]] production in the proximal renal tubules found in the [[kidney]], and intestinal mucosal cells found in the [[small intestine]]. Therefore, a symptom stemming from this disorder results in increased amounts of amino acids in the urine.
| | Iodized salt and other sources of iodine in the diet has eliminated this condition in many affluent countries, however there are a number of European countries, Australia, and New Zealand where iodine deficiency is a significant public health problem (Andersson M, Takkouche B, Egli I, Allen HE, de Benoist B. Current global iodine status and progress over the last decade towards the elimination of iodine deficiency. Bull World Health Organ 2005;83:518-25). However, it is still common in poorer nations. Also, treatment for conditions such as [[hypertension]] proscribe the excessive intake of salt and prescribe the use of a [[salt substitute]]. |
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| [[Pellagra]], a similar condition, is also caused by low nicotinamide; this disorder results in [[dermatitis]], [[diarrhea]], and [[dementia]].
| | ;Cretinism |
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| Hartnup disease is a disorder of amino acid transport in the intestine and kidneys; otherwise, the intestine and kidneys function normally, and the effects of the disease occur mainly in the brain and skin. Symptoms may begin in infancy or early childhood, but sometimes they begin as late as early adulthood. Symptoms may be triggered by sunlight, fever, drugs, or emotional or physical stress. A period of poor nutrition nearly always precedes an attack. The attacks usually become progressively less frequent with age. Most symptoms occur sporadically and are caused by a deficiency of niacinamide. A rash develops on parts of the body exposed to the sun. Mental retardation, short stature, headaches, unsteady gait, and collapsing or fainting are common. Psychiatric problems (such as anxiety, rapid mood changes, delusions, and hallucinations) may also result.<ref name="Merck">{{cite web | url=http://www.merck.com/mmhe/sec11/ch146/ch146h.html | title=Hartnup Disease | accessdate=2008-11-23 }}</ref>
| | ==Epidemiology and Demographics== |
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| ==Causes==
| | Certain areas of the world, due to natural deficiency and governmental inaction, are severely affected by iodine deficiency, which effects approximately two billion people worldwide. It is particularly common in the Netherlands, Western Pacific, South-East Asia and Africa. |
| Hartnup disease is inherited as an [[autosomal recessive]] trait. [[Heterozygote]]s are normal. [[Consanguinity]] is common. The failure of [[Membrane transport protein|amino-acid transport]] was reported in 1960 from the increased presence of [[indole]]s (bacterial metabolites of tryptophan) and tryptophan in the urine of patients as part of a generalized [[aminoaciduria]] of the disease. The excessive loss of tryptophan from [[malabsorption]] was the cause of the pellagra like symptoms. From studies on ingestion of tryptophan it seemed that there was a generalized problem with amino-acid transport.<ref>Milne, M.D., Crawford, M.A., Girao, C.B. and Loughridge, L. (1961) The metabolic disorder of the Hartnup disease. Q. J. Med. 29: 407-421</ref> In 2004, a causative gene, ''SLC6A19'', was located on band 5p15.33. ''SLC6A19'' is a sodium-dependent and chloride-independent neutral amino acid transporter, expressed predominately in the kidneys and intestine.<ref name=eMedicine>{{ cite web | url=http://www.emedicine.com/derm/byname/hartnup-disease.htm | title=Hartnup Disease | author=Lidija Kandolf Sekulovic | accessdate=2008-11-23 }}</ref>
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| ==Diagnosis==
| | India is the most outstanding, with 500 million suffering from deficiency, 54 million from goitre, and two million from [[cretinism]]. |
| The defective gene controls the absorption of certain amino acids from the intestine and the reabsorption of those amino acids in the kidneys. Consequently, a person with Hartnup disease cannot absorb amino acids properly from the intestine and cannot reabsorb them properly from tubules in the kidneys. Excessive amounts of amino acids, such as tryptophan, are excreted in the urine. The body is thus left with inadequate amounts of amino acids, which are the building blocks of proteins. With too little tryptophan in the blood, the body is unable to make a sufficient amount of the B-complex vitamin niacinamide, particularly under stress when more vitamins are needed.<ref name="Merck"/>
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| In Hartnup disease, urinary excretion of proline, hydroxyproline, and arginine remains unchanged, differentiating it from other causes of generalized aminoaciduria, such as Fanconi syndrome.
| | Among other nations affected by iodine deficiency, China and Kazakhstan have begun taking action, while Russia has not. Successful campaigns for the adoption of the use of iodized salt require education and regulation of salt producers and sellers and a communication campaign directed at the public, the salt trade, politicians and policy makers. The cost of adding iodine to salt is negligible. <ref>[http://www.nytimes.com/2006/12/16/health/16iodine.html "In Raising the World’s I.Q., the Secret's in the Salt"], article by Donald G. McNeil, Jr., December 16, 2006, ''New York Times''</ref> |
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| With urine chromatography, increased levels of neutral amino acids (e.g., glutamine, valine, phenylalanine, leucine, asparagine, citrulline, isoleucine, threonine, alanine, serine, histidine, tyrosine, tryptophan) and indican are found in the urine.
| | ==Related Chapters== |
| | *[[Basil Hetzel]] |
| | *[[Lugol's iodine]] |
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| Increased urinary Indican can be tested by Obermayer test.
| | ==References== |
| | | {{reflist|2}} |
| ==Treatment== | |
| A [[high-protein diet]] can overcome the deficient transport of neutral amino acids in most patients. Poor nutrition leads to more frequent and more severe attacks of the disease, which is otherwise asymptomatic. All patients who are symptomatic are advised to use physical and chemical protection from sunlight: avoid excessive exposure to sunlight, wear protective clothing, and use chemical sunscreens with a [[sun protection factor|SPF]] of 15 or greater. Patients also should avoid other aggravating factors, such as photosensitizing drugs, as much as possible. In patients with niacin deficiency and symptomatic disease, daily supplementation with nicotinic acid or nicotinamide reduces both the number and severity of attacks. Neurologic and psychiatric treatment is needed in patients with severe central nervous system involvement.<ref name=eMedicine />
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| == See also ==
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| * [[Citrullinemia]]
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| * [[Cystinosis]]
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| * [[Cystinuria]]
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| ==References==
| | {{Endocrine pathology}} |
| {{reflist}} | | [[Category:Iodine|Deficiency]] |
| | [[Category:Malnutrition]] |
| | [[Category:Endocrinology]] |
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| == External links ==
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| * [http://www.umm.edu/ency/article/001201.htm University of Maryland]
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| {{Amino acid metabolic pathology}}
| | [[ja:ヨード欠乏症]] |
| {{Membrane transport protein disorders}}
| | [[sv:Jodbrist]] |
| | [[zh:碘缺乏病]] |
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| [[Category:Rare diseases]]
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| [[Category:Amino acid metabolism disorders]]
| | {{WikiDoc Sources}} |
| [[Category:Autosomal recessive disorders]]
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| [[Category:Skin conditions resulting from errors in metabolism]]
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| [[Category:Membrane transport protein disorders]]
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For patient information click here
Template:Search infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-632-7753
Overview
Iodine is an essential trace element; the thyroid hormones thyroxine and triiodotyronine contain iodine. In areas where there is little iodine in the diet—typically remote inland
areas where no marine foods are eaten—iodine deficiency gives rise to
goiter (so-called endemic goitre), as well as cretinism, which results in developmental delays and other health problems
In some such areas, this is now combatted by the addition of small amounts of iodine to table salt in form of sodium iodide, potassium iodide, potassium iodate—this product is known as iodized salt. Iodine compounds have also been added to other foodstuffs, such as flour, in areas of deficiency.
Pathophysiology
Goitre
Low amounts of thyroid hormones in the blood, due to lack of iodine to make them, give rise to high levels of the pituitary hormone TSH, which in turn stimulate abnormal growth of the thyroid gland, sometimes causing goitres.
Iodized salt and other sources of iodine in the diet has eliminated this condition in many affluent countries, however there are a number of European countries, Australia, and New Zealand where iodine deficiency is a significant public health problem (Andersson M, Takkouche B, Egli I, Allen HE, de Benoist B. Current global iodine status and progress over the last decade towards the elimination of iodine deficiency. Bull World Health Organ 2005;83:518-25). However, it is still common in poorer nations. Also, treatment for conditions such as hypertension proscribe the excessive intake of salt and prescribe the use of a salt substitute.
- Cretinism
Epidemiology and Demographics
Certain areas of the world, due to natural deficiency and governmental inaction, are severely affected by iodine deficiency, which effects approximately two billion people worldwide. It is particularly common in the Netherlands, Western Pacific, South-East Asia and Africa.
India is the most outstanding, with 500 million suffering from deficiency, 54 million from goitre, and two million from cretinism.
Among other nations affected by iodine deficiency, China and Kazakhstan have begun taking action, while Russia has not. Successful campaigns for the adoption of the use of iodized salt require education and regulation of salt producers and sellers and a communication campaign directed at the public, the salt trade, politicians and policy makers. The cost of adding iodine to salt is negligible. [1]
Related Chapters
References
sv:Jodbrist
Template:WikiDoc Sources