Samples obtained from the original NBS specimens of confirmed cases with [beta]-cystathionine synthase deficiency (n = 4), propionyl-CoA carboxylase deficiency (n = 2), methylmalonyl-CoA mutase deficiency (n = 4), Cbl C deficiency (n = 7), various remethylation disorders [methylenetetrahydrofolate reductase (MTHFR), n = 3; Cbl G, n = 3; Cbl D variant 1, n = 1], and maternal vitamin [B.
3]-AC Propionyl-CoA carboxylase deficiency [up arrow] (propionic acidemia) (a) [up arrow] Methylmalonyl-CoA mutase deficiency [up arrow] to ([Mut.
Patients are deficient in propionyl-CoA
carboxylase (PCC), an enzyme that utilizes certain amino acids found in protein.
Propionyl-CoA is an intermediate in the degradation of several amino acids.
Children with this condition potentially have the greatest elevations in C3-carnitine because of an immediate backup of metabolic flux resulting in increased concentrations of propionyl-CoA.
PA results from a deficiency of mitochondrial propionyl-CoA carboxylase, an enzyme that requires biotin as a cofactor and converts propionyl-CoA to D-methylmalonyl-CoA.
It has been established, however, that several alternate pathways of propionyl-CoA metabolism that exist as minor pathways in healthy individuals are used extensively in patients with these diseases.
PA results from a defect in the enzyme propionyl-CoA carboxylase, which catalyzes the biotin-dependent conversion of propionyl-CoA to methylmalonyl-CoA (8).
The level of propionyl carnitine is highly increased in both diseases, arising from the transesterification of propionyl-CoA (Fig.
carboxylase deficiency with overflow of metabolites of isoleucine catabolism at all levels.
An example is increased propionylcarnitine (C3-acylcarnitine), a finding that requires differentiation of several disorders: propionyl-CoA
carboxylase deficiency, methylmalonyl-CoA mutase deficiency, several cobalamin disorders, and even dietary deficiency of vitamin B1, This requires the expertise of clinical and biochemical geneticists and a variety of diagnostic tests.
PA is caused by deficiency of propionyl-CoA
carboxylase, whereas MMA results from deficiency of either methylmalonyl-CoA mutase or defects in the production of adenosylcobalamin.