Neonatal screening (NS) for
methylmalonic acidemia uses
propionylcarnitine (C3) as a primary index, which is insufficiently sensitive at detecting
methylmalonic acidemia caused by defects in the
adenosylcobalamin synthesis pathway. Moreover,
homocystinuria from
cystathionine β-synthase deficiency is screened by detecting
hypermethioninemia, but
methionine levels decrease in
homocystinuria caused by defects in
homocysteine remethylation. To establish NS detection of
methylmalonic acidemia and
homocystinuria of these subtypes, we evaluated the utility of indices (1) C3 ≥ 3.6 μmol/L and C3/
acetylcarnitine (C2) ≥ 0.23, (2) C3/
methionine ≥ 0.25, and (3)
methionine < 10 μmol/L, by retrospectively applying them to NS data of 59,207 newborns. We found positive results in 116 subjects for index (1), 37 for (2), and 15 for (3). Second-tier tests revealed that for index 1, methylmalonate (MMA) was elevated in two cases, and MMA and total
homocysteine (tHcy) were elevated in two cases; for index 2 that MMA was elevated in one case; and for index 3 that tHcy was elevated in one case. Though data were anonymized, two cases identified by index 1 had been diagnosed with maternal
vitamin B12 deficiency during NS.
Methylene tetrahydrofolate reductase deficiency was confirmed for the case identified by index 3, which was examined because an elder sibling was affected by the same disease. Based on these data, a prospective NS study is underway.