3-Methylglutaconic aciduria

Revision as of 13:48, 4 September 2012 by WikiBot (talk | contribs) (Robot: Automated text replacement (-{{WikiDoc Cardiology Network Infobox}} +, -<references /> +{{reflist|2}}, -{{reflist}} +{{reflist|2}}))
Jump to navigation Jump to search
3-Methylglutaconic aciduria
Error creating thumbnail: File missing
3-methylglutaconic acid
DiseasesDB 29831 Template:DiseasesDB2 Template:DiseasesDB2 Template:DiseasesDB2

WikiDoc Resources for 3-Methylglutaconic aciduria

Articles

Most recent articles on 3-Methylglutaconic aciduria

Most cited articles on 3-Methylglutaconic aciduria

Review articles on 3-Methylglutaconic aciduria

Articles on 3-Methylglutaconic aciduria in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on 3-Methylglutaconic aciduria

Images of 3-Methylglutaconic aciduria

Photos of 3-Methylglutaconic aciduria

Podcasts & MP3s on 3-Methylglutaconic aciduria

Videos on 3-Methylglutaconic aciduria

Evidence Based Medicine

Cochrane Collaboration on 3-Methylglutaconic aciduria

Bandolier on 3-Methylglutaconic aciduria

TRIP on 3-Methylglutaconic aciduria

Clinical Trials

Ongoing Trials on 3-Methylglutaconic aciduria at Clinical Trials.gov

Trial results on 3-Methylglutaconic aciduria

Clinical Trials on 3-Methylglutaconic aciduria at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on 3-Methylglutaconic aciduria

NICE Guidance on 3-Methylglutaconic aciduria

NHS PRODIGY Guidance

FDA on 3-Methylglutaconic aciduria

CDC on 3-Methylglutaconic aciduria

Books

Books on 3-Methylglutaconic aciduria

News

3-Methylglutaconic aciduria in the news

Be alerted to news on 3-Methylglutaconic aciduria

News trends on 3-Methylglutaconic aciduria

Commentary

Blogs on 3-Methylglutaconic aciduria

Definitions

Definitions of 3-Methylglutaconic aciduria

Patient Resources / Community

Patient resources on 3-Methylglutaconic aciduria

Discussion groups on 3-Methylglutaconic aciduria

Patient Handouts on 3-Methylglutaconic aciduria

Directions to Hospitals Treating 3-Methylglutaconic aciduria

Risk calculators and risk factors for 3-Methylglutaconic aciduria

Healthcare Provider Resources

Symptoms of 3-Methylglutaconic aciduria

Causes & Risk Factors for 3-Methylglutaconic aciduria

Diagnostic studies for 3-Methylglutaconic aciduria

Treatment of 3-Methylglutaconic aciduria

Continuing Medical Education (CME)

CME Programs on 3-Methylglutaconic aciduria

International

3-Methylglutaconic aciduria en Espanol

3-Methylglutaconic aciduria en Francais

Business

3-Methylglutaconic aciduria in the Marketplace

Patents on 3-Methylglutaconic aciduria

Experimental / Informatics

List of terms related to 3-Methylglutaconic aciduria


3-Methylglutaconic aciduria (MGA) is used to describe at least five different disorders that impair the body's ability to make energy in the mitochondria. As a result of this impairment, 3-methylglutaconic acid and 3-methylglutaric acid build up and can be detected in the urine.

3-Methylglutaconic acid is classified as an organic acid. The double carboxylic acid functions are the principal cause of the strength of this acid. 3-methylglutaconic acid can be detected by the presence of the acid function and the double connection that involves reactivity with some specific substances.

Classification

There are currently 5 known subgroups of MGA; MGA type I,II,III,IV & V.

Type OMIM Gene Locus Also known as/Description
Type I 250950 AUH Chr.9 3-Methylglutaconic aciduria type I, 3-Methylglutaconic acidemia or 3-Methylglutaconyl-CoA Hydratase Deficiency[1]
Type II 302060 TAZ Xq28 Barth syndrome (BTHS), 3-Methylglutaconic aciduria type II or Cardiomyopathy-neutropenia syndrome
TYPE III 258501 OPA3 19q13.2-q13.3 3-Methylglutaconic aciduria type III or Costeff syndrome[2]
TYPE IV 250951 3-Methylglutaconic aciduria type IV
TYPE V 610198 DNAJC19 3q26.3 3-Methylglutaconic aciduria type V


Epidemiology

3-Methylglutaconic aciduria, seems to be most prevalent amongst the Jewish population of Iraq. However, a high concentration of one type is found in the Saguenay region of Canada. This tends to show that the disease is more frequent in insular areas where there is more chance that both parents be carriers, a higher birth rate, and higher number of congenital marriages. As all types of 3-Methylglutaconic aciduria are known to be genetic diseases and show a recessive pattern it is likely that congenital marriages where both partners are carriers increase the chance to have a baby with the condition.

The four major forms of 3-methylglutaconic aciduria are numbered types I, II, III, and IV. Types I-III are caused by mutations in three different genes and have distinct signs and symptoms. The genetic cause of 3-methylglutaconic aciduria type IV has not been established.

Symptoms

The characteristic features of 3-methylglutaconic aciduria type I include speech delay, delayed development of both mental and motor skills (psychomotor delay), elevated levels of acid in the blood and tissues (metabolic acidosis), abnormal muscle tone (dystonia), and spasms and weakness affecting the arms and legs (spastic quadriparesis). Fewer than 20 cases of 3-methylglutaconic aciduria type I have been reported.

Barth syndrome is a common name for 3-methylglutaconic aciduria type II. The main features of Barth syndrome include a weakened and enlarged heart (dilated cardiomyopathy), recurrent infections due to low numbers of white blood cells (neutropenia), skeletal problems, and delayed growth. The incidence of 3-methylglutaconic aciduria type II is approximately 1 in 200,000 male infants.

Costeff optic atrophy syndrome is another name for 3-methylglutaconic aciduria type III. This disorder is characterized mainly by the degeneration of the optic nerves, which carry information from the eyes to the brain. Sometimes other nervous system problems occur, such as an inability to maintain posture, poor muscle tone, the development of certain involuntary movements (extrapyramidal dysfunction), and a general decrease in brain function (cognitive deficit). The incidence of 3-methylglutaconic aciduria type III is about 1 in 10,000 newborns in the Iraqi Jewish population. This disorder is extremely rare in all other populations.

The signs and symptoms of 3-methylglutaconic aciduria type IV are variable and overlap with types I-III. The incidence of 3-methylglutaconic aciduria type IV is unknown.

Genetics

Mutations

Mutations in the AUH, OPA3, and TAZ genes cause 3-methylglutaconic aciduria.

  • Mutations in the AUH gene cause 3-methylglutaconic aciduria type I. This gene provides instructions for producing 3-methylglutaconyl-CoA hydratase, an enzyme that is involved in processing the amino acid leucine. This amino acid is broken down in the mitochondria during the process of energy production. A deficiency of this enzyme leads to a buildup of 3-methylglutaconic acid, which is eliminated in the urine. Researchers believe that other genes or environmental factors also contribute to the development of this disorder.
  • Mutations in the TAZ gene cause 3-methylglutaconic aciduria type II (Barth syndrome). This gene provides instructions for making a protein called tafazzin. This protein plays a critical role in maintaining the levels of a particular lipid, called cardiolipin, located in the inner membrane of the mitochondria. A lack of tafazzin results in abnormalities in the structure and function of mitochondria, leading to the heart defects and other problems seen in this disorder.
  • Mutations in the OPA3 gene cause 3-methylglutaconic aciduria type III. This gene carries instructions for making a protein that is also found in mitochondria, but whose function is unknown. Researchers have suggested that cells with a defective OPA3 protein are more susceptible to a process that eliminates damaged or unneeded cells (programmed cell death called apoptosis).
  • The genetic factors involved in causing 3-methylglutaconic aciduria type IV are unknown.

Inheritance patterns

The inheritance patterns of 3-methylglutaconic aciduria differ depending on the gene involved.

  • Types I and III are inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.
  • Type II is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
  • The inheritance pattern of 3-methylglutaconic aciduria type IV is unknown.

References

External links

it:3-metilglutaril aciduria

Template:JB1

Template:WikiDoc Sources