Short-chain acyl-CoA dehydrogenase deficiency (SCAD)
Log in to starLast updated 2mo ago
A newborn screen flags elevated C4 (butyrylcarnitine). The infant is asymptomatic. Urine organic acids show elevated ethylmalonic acid. Sequencing identifies two ACADS variants, including the common c.625G>A susceptibility variant.
AR; ACADS. Two common variants (c.511C>T and c.625G>A) are best understood as susceptibility variants: very common in the general population (c.625G>A homozygosity ~5-7%; up to ~14% are homozygous or compound heterozygous for the two common variants combined) and not consistently associated with disease.
- Clinical significance is uncertain. Most NBS-detected infants remain asymptomatic.
- Reported (but inconsistent) features: hypotonia, developmental delay, lethargy, episodic hypoglycemia during illness
- Biochemistry: elevated C4 acylcarnitine on NBS; elevated ethylmalonic acid (EMA) on urine organic acids
- Several states have removed SCAD from their NBS panel due to the uncertain phenotype-genotype correlation
- Differential for elevated C4 includes ethylmalonic encephalopathy and isobutyryl-CoA dehydrogenase deficiency
- Newborn screening: elevated C4 (butyrylcarnitine) on acylcarnitine profile (several states have removed SCAD from their panel)
- Urine organic acids: elevated ethylmalonic acid
- Confirm with ACADS sequencing; interpret cautiously given the common c.511C>T and c.625G>A susceptibility variants
- For symptomatic patients: avoid prolonged fasting
- Many infants need only reassurance and routine follow-up
- Riboflavin supplementation is sometimes trialed (cofactor for the dehydrogenase) but evidence is limited
SCAD is the FAO "incidentaloma" of newborn screening. Elevated C4 with little or no disease in most carriers. Counseling families requires acknowledging this uncertainty up front.
C4 = SCAD; C8 = MCAD; C14:1 = VLCAD; C16-OH = LCHAD/TFP. The chain-length number tracks the deficient enzyme.