Clinical aspects of short-chain acyl-CoA dehydrogenase deficiency.
Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of mitochondrial fatty acid oxidation. SCADD is biochemically characterized by increased C4-carnitine in plasma and ethylmalonic acid in urine. The diagnosis of SCADD is confirmed by DNA analysis showing SCAD gene mutations and/or variants. SCAD gene variants are present in homozygous form in approximately 6% of the general population and considered to confer susceptibility to development of clinical disease. Clinically, SCADD generally appears to present early in life and to be most frequently associated with developmental delay, hypotonia, epilepsy, behavioral disorders, and hypoglycemia. However, these symptoms often ameliorate and even disappear spontaneously during follow-up and were found to be unrelated to the SCAD genotype. In addition, in some cases, symptoms initially attributed to SCADD could later be explained by other causes. Finally, SCADD relatives of SCADD patients as well as almost all SCADD individuals diagnosed by neonatal screening remained asymptomatic during follow-up. This potential lack of clinical consequences of SCADD has several implications. First, the diagnosis of SCADD should never preclude extension of the diagnostic workup for other potential causes of the observed symptoms. Second, patients and parents should be clearly informed about the potential lack of relevance of the disorder to avoid unfounded anxiety. Furthermore, to date, SCADD is not an optimal candidate for inclusion in newborn screening programs. More studies are needed to fully establish the relevance of SCADD and solve the question as to whether SCADD is involved in a multifactorial disease or represents a nondisease.
van Maldegem
Bianca T
BT
Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. b.van.maldegem@gelre.nl
Wanders
Ronald J A
RJ
Wijburg
Frits A
FA
D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency / Q000235:genetics; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics / Q000628:therapy; D008928:Mitochondria / Q000201:enzymology*; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D015997:Neonatal Screening; D010084:Oxidation-Reduction; D010641:Phenotype
D015415:Biomarkers; D005227:Fatty Acids; D042964:Acyl-CoA Dehydrogenase