Therefore, NBS for IVA may also detect patients with 2-methylbutyrylCoA dehydrogenase (short/branched-chain acyl-CoA dehydrogenase) deficiency (SBCADD, OMIM #610006) caused by mutations in acyl-CoA dehydrogenase, short/branched chain (ACADSB) (600301) (2).
A total of 24 cases of IVA and 3 cases of SBCADD were detected (Fig.
The resulting total incidence for IVA was 1:67 000 (95% CI: 1:45 000-1:107 000), whereas the total incidence for SBCADD was 1:403 000 (95% CI: 1:161 0001:1 612 000).
With this strategy all cases of IVA, including the variant cases, but only 1 of the 4 cases of SBCADD would have been detected.
Such a strategic change is in line with the current German NBS disease panel initiated in 2005, which does not include SBCADD. This decision rested upon the questionable benefit of neonatal screening for SBCADD, considering that the exact natural history and pathogenicity of this condition have not been delineated to date.
 Nonstandard abbreviations: IVA, isovaleric acidemia; CoA, coenzyme A; C5, isovalerylcarnitine; NBS, newborn screening; SBCADD, short/branched-chain acyl-CoA dehydrogenase (2-methylbutyryl-CoA dehydrogenase) deficiency; PPV, positive predictive value; ESI-MS/MS, electrospray ionization-tandem mass spectrometry; C8, octanoylcarnitine; C4, butyrylcarnitine; C3, propionylcarnitine.
Short/branched-chain acylCoA dehydrogenase deficiency (SBCADD; (5) OMIM +600301) is an autosomal recessively inherited defect in isoleucine catabolism.
Judging by the number of diagnosed patients, SBCADD would appear to be a rare disorder.
In this report we show that increased excretion of 2-ethylhydracrylic acid (2-EHA) is a prominent and easily recognized abnormality on analysis of organic acids in urine from patients with SBCADD. Awareness of 2-ethylhydracrylic aciduria as an indicator of SBCADD may lead to increasing diagnosis of this disorder and further definition of its phenotype.
Patient 1 with SBCADD was identified by newborn screening and is healthy with normal development, whereas patients 2-4 were identified after metabolic studies performed for evaluation of clinical disease.
In all samples there was increased excretion not only of 2-MBG, as expected in SBCADD, but also of 2-EHA.
In the samples from the SBCADD patients, the height of the 2-EHA peak always exceeded that of the 2-MBG peak, with the exception of patient 4 (Fig.