A Rare Case of Short-Chain Acyl-COA Dehydrogenase Deficiency: The Apparent Rarity of the Disorder Results in Under Diagnosis

Short-chain acyl-CoA dehydrogenase (ACAD) deficiency is an extremely rare inherited mitochondrial disorder of fat metabolism. This belongs to a group of diseases known as fatty acid oxidation disorders. Screening programmes have provided evidence that all the fatty acid oxidation disorders combined are among the most common inborn errors of metabolism. Mitochondrial beta oxidation of fatty acids is an essential energy producing pathway. It is a particularly important pathway during prolonged periods of starvation and during periods of reduced caloric intake due to gastrointestinal illness or increased energy expenditure during febrile illness. The most common presentation is an acute episode of life threatening coma and hypoglycemia induced by a period of fasting due to defective hepatic ketogenesis. Here, the case of a 4 month old female patient who had seizures since the third day of her birth and persistent hypoglycemia is described. She was born to parents of second degree consanguinity after 10 years of infertility treatment. There was history of delayed cry after birth. Metabolic screening for TSH, galactosemia, 17-OHP, G6PD, cystic fibrosis, biotinidase were normal. Tandem mass spectrometric (TMS) screening for blood amino acids, organic acids, fatty acids showed elevated butyryl carnitine (C4) as 3.40 μmol/L (normal <2.00 μmol/L), hexanoyl carnitine (C6) as 0.92 μmol/L (normal <0.72 μmol/L), C4/C3 as 2.93 μmol/L (normal <1.18 μmol/L). The child was started immediately on carnitor syrup (carnitine) 1/2 ml twice daily. Limitation of fasting stress and dietary fat was advised. Baby responded well by gaining weight and seizures were controlled. Until now, less than 25 patients have been reported worldwide. The limited number of patients diagnosed until now is due to the rarity of the disorder resulting in under diagnosis

The difference between observed and expected prevalence of MCAD deficiency in The Netherlands: a genetic epidemiological study

Medium chain acyl coenzyme A dehydrogenase (MCAD) deficiency is assumed to be the most common inherited disorder of mitochondrial fatty acid oxidation. Few reports mention the difference between the expected and observed prevalence of MCAD deficiency on the basis of the carrier frequency in the population. We performed a population-wide retrospective analysis of all known MCAD-deficient patients in The Netherlands. In this study, the observed prevalence of MCAD deficiency in The Netherlands was 1/27 400 (95% confidence interval (CI) 1/23 000-1/33 900), significantly different from the expected prevalence of 1/12 100 (95% CI 1/8450-1/18 500). The observed prevalence of MCAD deficiency showed a remarkable north-south trend within the country. From the patients in this cohort, it can be observed that underdiagnosis contributes to a larger extent to the difference between the expected and observed prevalences of MCAD deficiency in our country, than reduced penetrance. We determined estimates of the segregation proportion in a cohort of 73 families under the assumption of complete ascertainment (p(LM) = 0.41, 95% CI 0.31-0.51) and single ascertainment (p(D) = 0.28, 95% CI 0.19-0.37). With the expectation-maximization algorithm, a third estimate was obtained (p(EM) = 0.28, 95% CI 0.20-0.37). The agreement between the latter two estimates supports incomplete selection and the segregation proportions were in agreement with normal mendelian autosomal recessive inheritanc