Maple syrup urine disease 2011

Summary

The maple syrup urine (MSUD) disease is an autosomal recessive disorder which is caused by a disturbance in the amino acid metabolism. The symptomes of MSUD are mental and physical retardation, feeding problems, vomiting, dehydration, lethargy, hypotonia, seizures, hypoglycaemia, ketoacidosis, opisthotonus, pancreatitis, coma and neurological decline. If the disease remains unrecognized it can also lead to brain damage and in the last resort to death. The most characteristical symptome is the sweet smell of the urine, just like maple syrup.

Phenotype

The MSUD occurs because of a defect in the branched-chain alpha-keto acid dehydrogenase complex (BCKDC). This defect leads to a block in oxidative decarboxylation which results in a rising concentration of branched-chain amino acids (BCAA) and their toxic by-products in blood and urine. The MSUD can be divided in 5 subtypes:

- Classic Severe MSUD

 The classic form of MSUD is the worst one of this disease. The level of  the BCAAs are dramatically high in blood, urine and cerebrospinal
 fluid and the BCKD activity is less than 2% of normal.
 The children seams normal at birth but after 4 to 7 days after birth the first symptoms like lethargy and little interest in feeding appear. 
 With progress of the disease it comes to weight loss and progressive neurological deterioration and hypo- to hypertonia. If the disease is  
 not treated it leads to coma and death within several months after birth .

- Intermediate MSUD

 In the intermediate MSUD the level of BCAAS in blood and urine rises permanent and the neurological impairment becomes worse. The level of 
 BCKD ranges from 3% to 30% of normal. In many cases the acute metabolic decompensation do not occur.

 

- Intermittent MSUD

 Patients with the intermittent MSUD develop normal. In normal life situations these people have no symptoms and also a normal level of  
 BCAAS. But in stress situations acute metabolic decompensations arise. The level of activity of BCKD ranges from 5% to 50% of normal. 
 Symptoms can appear between 5 months to 2 years of age when the patients have an infection.

- Thiamine-responsive MSUD

- E3-Deficient MSUD with Lactic Acidosis

Cross-references

See also description of this disease in

• Wikipedia
• OMIM
• Genetics Home Reference
• MedlinePlus
• Medscape
• NCBI
• NORD
• PubMed
• Medical Biochemistry Page

Biochemical disease mechanism

The example protein is involved in the example pathway...

Ideally, include a graphical pathway representation.

(see above: own words, no plagiarism)

Cross-references

• link to KEGG
• link to MetaCyc

... see databases in "resources"

Mutations

Current knowledge about mutations associated with the disease. - Separate into disease causing and neutral mutations.

Reference sequence

Which sequence does not cause the disease and is most often found in the population.

• Create a page for the reference sequence. -- These sequence pages will be the starting point for collecting prediction results and result discussions.

Neutral mutations

• Create one page per mutated sequence.

Disease causing mutations

• Create one page per mutated sequence.