We describe these children and their metabolic findings with emphasis on their newborn screening octanoylcarnitine (C8) level, the primary marker for newborn detection of MCADD. We also performed a literature search of cases of sudden death in MCADD in which the clinical status preceding death is described.
The newborn screening C8 levels in our four cases were markedly elevated, ranging from 8.4 to 24.8 μmol/L (cut off < 0.8 μmol/L). Only two of the children were homozygous for the common c.985A>G MCAD mutation; the other two were heterozygous for this mutation. Similarly, among the eight reported cases which included MCAD genotypes, five were homozygous for the c.985A>G mutation, while two were heterozygous and one was homozygous for a splice site mutation. Vomiting 12–24 h before sudden death was present in all four of our cases, and the review of reported cases of sudden death in MCADD disclosed vomiting as a frequent symptom.
We suggest that in MCADD (1) a newborn screening C8 level of 6 μmol/L or greater represents particular risk of sudden death; (2) that MCAD genotypes other than homozygosity for the c.985A>G mutation are also associated with sudden death; (3) that vomiting is a frequent symptom preceding sudden death; and (4) social support and medical follow-up of these families are crucial in reducing the occurrence of sudden death.