Maple Syrup Urine Disease

From Iusmgenetics

Contents 1 Maple Syrup Urine Disease 1.1 General background information 1.2 Mode of inheritance 1.3 Single important gene 1.4 Etiology 1.5 Pathogenesis 1.6 Phenotypic information 1.7 Diagnosis 1.8 Treatment 1.9 Recent research 1.10 5 important facts 1.11 Not to be confused with 1.12 Questions and answers

Maple Syrup Urine Disease

General background information

• A deficiency of branched chain ketoacid dehydrogenase (BCKD)
• 1 / 200K
  • Higher in Mennonites of Lancaster County, PA background

Mode of inheritance

• Autosomal recessive

Single important gene

• Branched chain ketoacid dehydrogenase (BCKD) is a large, multi-subunit enzyme complex composed of proteins from at least 6 loci.
• Branched chain keotacid dehydrogenase is the rate-limiting, irreversible step of branched-chain metabolism.

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.
• 

Pathogenesis

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

Diagnosis

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

Recent research

5 important facts

Not to be confused with

Questions and answers