[Short-chain acyl-CoA dehydrogenase deficiency (SCADD): relatively high prevalence in the Netherlands and strongly variable fenotype; neonatal screening not indicated].
OBJECTIVE
To describe the clinical, genetic, and biochemical characteristics of short-chain acyl-CoA dehydrogenase deficiency (SCADD), a clinically heterogeneous metabolic disorder for which neonates are screened for in parts of the United States and Australia. To explore the genotype-phenotype relation and to discuss neonatal screening for SCADD.


METHODS
Retrospective study of 31 Dutch SCADD patients and 8 SCADD relatives.


METHODS
Patients and relatives were included ifbiochemical SCADD characteristics (increased C4-carnitine and/or ethylmalonic acid) were present in combination with a mutation and/or the c.511C>T or c.625G>A variant on each SCAD-encoding (ACADS) allele. The patients were subdivided into 3 genotype groups: mutation/mutation, mutation/variant and variant/variant group.


RESULTS
A birth prevalence for SCADD of at least 1:50,000 was calculated. Most patients presented before the age of 3 years, mainly with developmental delay, epilepsy, behavioural disturbances and/or hypoglycaemia. The ACADS genotype showed a statistically significant association with biochemical, but not with clinical characteristics. In total 7 out of 8 SCADD relatives were free of symptoms. In 5 of the 31 patients, of whom 2 had severe symptoms, a second diagnosis was made which might explain the symptoms.


CONCLUSIONS
SCADD was far more common than had previously been assumed and clinical symptoms in SCADD were non-specific, often transient or absent and not correlated with specific ACADS genotypes. SCADD does not meet major neonatal screening criteria and is therefore not suited for inclusion in neonatal screening programmes.
van Maldegem
B T
BT
Afd. Kindergeneeskunde, Academisch Medisch Centrum/Universiteit van Amsterdam, Amsterdam. b.t.vanmaldegem@amc.uva.nl
Duran
M
M
Wanders
R J A
RJ
Niezen-Koning
K E
KE
Hogeveen
M
M
Ijlst
L
L
Waterham
H R
HR
Wijburg
F A
FA