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Short chain acyl-CoA dehydrogenase deficiency
Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a very rare inborn error of mitochondrial fatty acid oxidation characterized by variable manifestations ranging from asymptomatic individuals (in most cases) to those with failure to thrive, hypotonia, seizures, developmental delay and progressive myopathy.
Approximately 50 patients have been identified worldwide to date. The Netherlands has an estimated birth prevalence of at least 1/50,000.
Most infants with SCAD deficiency identified through newborn screening programs have been well at the time of diagnosis and most have remained asymptomatic. In affected individuals manifestations include seizures, developmental delay (delayed sitting/walking and/or speech/social interaction), failure to grow with poor feeding, and usually muscle weakness and hypotonia.
Symptomatic SCAD deficiency is due to mutations in the acyl-CoA dehydrogenase, C-2 to C-3 short chain ACADS gene (12q24.31) as well as additional as yet unidentified precipitating factors.
SCAD deficiency has been defined as the presence of (1) increased butyrylcarnitine (C4) concentrations in plasma and/or increased ethylmalonic acid (EMA) concentrations in urine under non-stressed conditions (on at least two occasions) and (2) biallelic ACADS mutations or susceptibility variants 511C>T and 625G>A. Newborn screening programs in Austria, Hungary and Iceland now usually identify patients with SCAD deficiency at birth. Asymptomatic relatives may meet the diagnostic criteria for SCAD deficiency.
Differential diagnoses include multiple acyl-CoA dehydrogenase deficiency (MADD), ethylmalonic encephalopathy and acute ackee fruit intoxication (see these terms).
Antenatal diagnosis is not relevant as asymptomatic and symptomatic family members can have the same SCAD genotype.
SCAD deficiency is inherited in an autosomal recessive manner and genetic counseling is possible.
Management and treatment
Most patients are asymptomatic and no treatment is needed. Some symptomatic patients are given riboflavin and follow a low fat/high carbohydrate diet and avoid fasting. Acute metabolic acidosis can be treated by the administration of high levels of dextrose (with or without insulin) and IV fluids. Seizures can be treated with anticonvulsants but valproate should be avoided. Pregnancies should be monitored for complications such as acute fatty liver of pregnancy and preeclampsia (see these terms). Follow-up at a metabolic clinic should include the regular assessment of growth and development and nutritional status of patients.
The prognosis is good in asymptomatic patients but variable in those who display the disease manifestations.