Biochemical defect: deficiency of isovaleryl coenzyme Q dehydrogenase which is an enzyme involved in leucine catabolism.
Inheritance: autosomal recessive
Phenotypic patterns:
(1) acute, severe with death in infancy
(2) chronic intermittent
Attacks may be precipitated by:
(1) failure to adhere to a protein restricted diet or exposure to protein rich food
(2) increased protein catabolism associated with fever or physical training
Clinical findings in the chronic form:
(1) family history of isovaleric acidemia
(2) vomiting with dehydration
(3) lethargy with reduced level of consciousness (stupor, coma)
(4) seizures
(5) odor of sweaty feet
(6) diarrhea
(7) alopecia
(8) psychomotor development may range from normal to severe mental retardation
(9) heart failure or conduction defects (associated with carnitine deficiency)
Laboratory findings:
(1) acidosis
(2) ketonuria
(3) pancytopenia
(4) hyperglycemia
(5) increased plasma short chain fatty acids (isovaleric acid, isovalerylglycine, isovaleryl carnitine, 3-hydroxyisovaleric acid)
(6) elevated urinary isovalerylglycine (at all times, further during an attack)
(7) elevation of other nonvolatile organic acids in the urine during an attack (3-hydroxyisovaleric acid, others)
(8) elevated serum ammonia
(9) carnitine deficiency during an attack
Management:
(1) The diet should be protein restricted.
(2) The clinical status is improved with supplemental dietary carnitine and glycine.
