Maple syrup urine disease

Maple syrup urine disease :

·     It is an autosomal recessive metabolic disorder affecting branched-chain amino acid.

·     It is a type of organic acidemia.

·     It is rare, and age of onset: infancy, neonatal, childhood.

·     MSUD is caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase complex ( BCKDC), leading to a buildup of branched-chain amino acid (leucine, isoleucine, and valine) and their toxic by-products (ketoacids) in the blood and urine.

·     BCKDC consists of 4 subunits: E1a, E1b, E2, E3. Mutation in the any of four of these Genes causes MSUD: BCKDHA, BCKDHB, DBT, and DLD.

·     Mutation in any of these gene reduces or eliminate the function of the enzyme complex, preventing the normal breakdown.

·     Leucine, isoleucine and valine are present in meat, fish, soy, eggs, nuts, seeds, grains and pulses.

·     Diagnosis:

·     There are several variations of the disease:

·     Classic severe MSUD: little enzyme activity.

·     Intermediate MSUD: slightly higher EA

·     Intermittent MSUD: significant EA, doesn't affect growth.

·     Thiamine- responsive MSUD: after infancy

·     E3- deficient MSUD with lactic acidosis

·     Accumulation of these 3 amino acids and their alpha-keto acids leads to encephalopathy and progressive neurodegenerative in untreated infants.

·     The urine of these infants had an odor of maple syrup ( burnt sugar).

·     Symptoms: lethargy, weight loss, odor, alternating episodes of hypertonia (muscle rigidity) and hypotonia ( limpness), high pitched cry, delayed development, seizures, feeding problem, strong smell in ear wax, anorexia, dehydration.

·     Management:

·     DNPH may be used to test urine for ketones ( a sign of metabolic decompensation)

·     Diet control

·     Liver transplant

·     Diagnosis: newborn blood-spot screening