Enzyme defects indicated by solid bars are numbered as follows: (1), branched-chain 2-ketoacid dehydrogenase complex deficiency (MSUD, maple syrup urine disease); (2), isovaleryl-CoA dehydrogenase deficiency (isovaleric acidemia); (3), isolated 3-methylcrotonyl-CoA
carboxylase deficiency; (4), 3-methylcrotonyl-CoA
carboxylase deficiency as part of a multiple carboxylase deficiency due to nutritional biotin deficiency or biotinidase deficiency or holocarboxylase synthetase deficiency or carbonic anhydrase VA deficiency or MT-ATP6 deficiency; (5), 3-methylglutaconyl-CoA hydratase deficiency; (6), 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase deficiency.
Through a pilot screening program, Giana was found to have an inherited metabolic disorder called 3-MCC (3-methylcrotonyl-CoA
This enzyme catalyzes the conversion of isovalery-CoA to 3-methylcrotonyl-CoA
, and a deficiency of this enzyme results in toxic accumulation of isovaleric acid and derivative organic acids.
We received a phone call from our children's pediatrician telling us that Damian's newborn screening had come back abnormal for 3-methylcrotonyl-CoA
carboxylase deficiency, or 3MCC.
3-MCC catalyzes the carboxylation of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA within the leucine catabolic pathway (Fig.
Deficiency of 3-MCC causes accumulation of 3-methylcrotonyl-CoA, which undergoes hydration to form 3-hydroxyisovaleryl-CoA (Fig.
Elevations in C5-OH acylcarnitine are indicative of a variety of pathologies, including 3-methylcrotonyl-CoA carboxylase deficiency, and have frequently resulted in a diagnosis of this deficiency in the mother rather than in the newborn (5).
* Newborn screen findings can reveal maternal defects in the case of several inborn errors of metabolism, including 3-methylcrotonyl-CoA carboxylase deficiency and carnitine transport defect, and also can reveal nutritional deficits in the mother.
Carboxylase Deficiency--Symptoms may include hypotonia, muscle atrophy, seizures, and dermatological changes.
The hydratase deficiency in these patients was identified by use of a radioactive enzyme assay measuring three consecutive steps of leucine degradation, from 3-methylcrotonyl-CoA
to acetoacetic acid (12).
C50H is increased in 3-methylcrotonyl-CoA
carboxylase deficiency, 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, and 3-methylglutaconyl-CoA hydratase deficiency, whereas 2-methyl-3-hydroxybutyrylcarnitine is increased in [beta]-ketothiolase deficiency and 2-methyl-3-hydroxybutyrl-CoA dehydrogenase deficiency (118).
[beta]-KETOTHIOLASE, 3-HYDROXY-3-METHYLGLUTARYL-COA LYASE (HMG), AND 3-METHYLCROTONYL-COA
CARBOXYLASE (MCC) DEFICIENCY AND MCD