Maple Syrup Urine Disease
From Iusmgenetics
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[edit] Maple Syrup Urine Disease
[edit] General background information
- A deficiency of branched chain ketoacid dehydrogenase (BCKD)
- 1 / 200K
- Higher in Mennonites of Lancaster County, PA background
[edit] Mode of inheritance
- Autosomal recessive
[edit] Single important gene
- Branched chain ketoacid dehydrogenase (BCKD) is a large, multi-subunit enzyme complex with at least 6 loci involved.
- Branched chain keotacid dehydrogenase is the rate-limiting, irreversible step of branched-chain metabolism.
[edit] Etiology
- When branched chain ketoacid dehydorgenase (BCKD) is non-functional, branched-chain amino acids and branched chain alpha-keto acids accumulate.
- Branch chain amino acids include leucine
- Branched chain amino acid and branched alpha-keto acid accumulation leads to neurologic disorders and development disruption.
[edit] Pathogenesis
[edit] Phenotypic information
- Classic
- Appear normal at birth
- First week of life: lethargy, weight loss, encephalopathy, acidosis, hyper-ammonemia
- Distinctive sweet odor of urine
- < 2% BCKD activity
- Intermediate:
- similar to classic
- later onset
- 3-30% BCKD activity
- Intermittent:
- symptoms and lab abnormalities only when other illnesses present
- Thiamine responsive:
- E2 protein mutations lend themselves to being treated with thiamin
[edit] Diagnosis
[edit] Treatment
- Decrease leucine in the diet
- Requires use of special medical food and measured amounts of natural foods.
- Early treatment significantly improves intellectual outcome
- Monitor leucine, isoleucine, and valine levels
- Urine dinitrophenylhydrazine (DNPH) test:
- The addition of 2,4-dinitrophenylhydrazine in HCl to urine gives a chalky white precipitate in the presence of ketoacids.
- Aggressive treatment of episodes of loss of metabolic control
- Liver transplant
- Thiamine responsive pts:
- E2 protein mutations lend themselves to being treated with thiamin
