View source for Maple syrup urine disease

'''For patient information, click [[Maple syrup urine disease (patient information)|here]]'''
{{DiseaseDisorder infobox |
  Name           = Maple syrup urine disease |
  ICD10          = {{ICD10|E|71|0|e|70}} |
  ICD9           = {{ICD9|270.3}} |
  ICDO           = |
  Image          = L-leucine-skeletal.png |
  Caption        = [[Leucine]] (pictured above), [[isoleucine]], and [[valine]] are the branched-chain amino acids which build up in MSUD. |
  OMIM           = 248600 |
  OMIM_mult      = |
  MedlinePlus    = 000373 |
  eMedicineSubj  = |
  eMedicineTopic = |
  DiseasesDB     = 7820 |
  MeshID         = D008375 |
}}
{{Search infobox}}
{{CMG}}

==Overview==
'''Maple syrup urine disease''' ('''MSUD''') is an autosomal recessive [[metabolic disorder]] of [[amino acid metabolism]]. It is also called '''branched chain ketoaciduria.'''

This '''amino acid acidopathy''' is due to a deficiency of the metabolic enzyme [[branched chain α-keto acid dehydrogenase]] (BCKDH) leading to a buildup of branched-chain [[amino acids]] ([[leucine]], [[isoleucine]], and [[valine]]) in the blood and urine.

==Presentation==
Characterized by an infant with sweet-smelling urine with an odor similar to that of maple syrup, infants with this disease seem healthy at birth but if left untreated suffer severe [[brain damage]] and eventually die. Because of the [[founder effect]], MSUD has a much higher prevalence in children of Amish and Mennonite descent. <ref>Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:77 ISBN 1591032016</ref> <ref>Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:68 ISBN 140510368X</ref>

From early infancy, the condition is characterized by poor feeding, [[vomiting]], lack of energy ([[lethargy]]), [[seizures]], and mental health issues. The urine of affected infants has a distinctive sweet odor, much like burned caramel, that gives the condition its name.

==Classification==

Maple syrup urine disease can be classified by its pattern of signs and symptoms or by its genetic cause. 

The most common and most severe form of the disease is the classic type, which appears soon after birth. Variant forms of the disorder appear later in infancy or childhood and are typically less severe, but still involve [[mental retardation|mental]] and physical retardation if not treated.

There are several variations of the disease:
*Classic Severe MSUD
*Intermediate MSUD
*Intermittent MSUD
*Thiamine-responsive MSUD
*E3-Deficient MSUD with Lactic Acidosis

==Treatment==

Treatment of the MSUD, like diabetes, requires careful monitoring of blood chemistry and involves both special diet and frequent testing. 

A diet with minimal levels of the amino acids leucine, isoleucine, and valine must be maintained in order to prevent neurological 
damage. Usually, patients, or parents of patients are assisted by a physician or dietician. This diet must be adhered to strictly and permanently. However, with proper treatment those afflicted are able to live healthy, normal lives and not suffer the severe neurological damage that characterizes the untreated disease.

==Genetics==
[[Image:autorecessive.jpg|thumb|left|Maple syrup urine disease is inherited in an [[Recessive gene|autosomal recessive]] pattern.]]
Maple syrup urine disease affects an estimated 1 in 185,000 infants worldwide.

Mutations in the following genes cause maple syrup urine disease:
* BCKDHA ({{OMIM|608348}}) 
* BCKDHB ({{OMIM|248611}})  
* DBT ({{OMIM|248610}}) 
* DLD ({{OMIM|238331}}) 

These four genes produce proteins that work together as the [[branched-chain alpha-keto acid dehydrogenase complex]]. The complex is essential for breaking down the amino acids [[leucine]], [[isoleucine]], and [[valine]], which are present in many kinds of food (particularly [[protein]]-rich foods such as milk, meat, and eggs). 

Mutations in any of these genes reduce or eliminate the function of the enzyme complex, preventing the normal breakdown of [[leucine]], [[isoleucine]], and [[valine]]. As a result, these amino acids and their by-products build up in the body. 

Because high levels of these substances are toxic to the [[brain]] and other organs, this accumulation leads to the serious medical problems associated with maple syrup urine disease. However recent breakthroughs have yielded treatments through liver transplants and gene therapy is on the rise.

==See also==
* [[inborn errors of metabolism]].

==References==
{{reflist|2}}

==Additional Resources==
* {{NLM|maplesyrupurinedisease}}
*[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.255&ref=toc Maple Syrup Urine Disease (Overview on NLM)]


{{SIB}}
{{Endocrine, nutritional and metabolic pathology}}
[[de:Ahornsirupkrankheit]]
[[fr:Maladie du sirop d'érable]]
[[ms:Penyakit Kencing Sirap Maple]]
[[pl:Choroba syropu klonowego]]
[[pt:Doença da urina em xarope de ácer]]
[[ru:Лейциноз]]

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[[Category:Genetic disorders]]
[[Category:Inborn errors of metabolism]]
[[Category:Mature chapter]]
[[Category:Disease]]
[[Category:Neurology]]