21 Clin Pathol:Mol Pathol 1997;50:212-217 Fatty acid oxidation disorders as primary cause of sudden and unexpected death in infants and young children: an investigation performed on cultured fibroblasts from 79 children who died aged between 0-4 years J B Lundemose, S Ko1vraa, N Gregersen, E Christensen, M Gregersen Abstract Background-Disorders of fatty acid me- tabolism are known to be responsible for cases of sudden and unexpected death in infancy. At least 14 disorders are known at present. 120 cases of sudden infant death syndrome (SIDS) had been examined for a prevalent mutation (G985) causing me- dium chain acyl CoA dehydrogenase defi- ciency, which is inherited in an autosomal recessive mode. No over-representation of either homozygous or heterozygous cases was found. Aimns-To investigate a broader spectrum of fatty acid oxidation disorders in a wider range of sudden deaths in infants and young children. Methods-Seventy nine cases of unex- pected death in infants and young children younger than 4 years old were examined for a minimum of nine fatty acid oxidation disorders, using the global [9,10-'H] myr- istic acid oxidation assay in cultured fibroblasts from achilles tendon biopsies taken at postmortem examination. Results-Three cases with fatty acid oxi- dation disorders and two carriers of the G985 mutation were found, all catagorised as non-SIDS or borderline SIDS. The glo- bal assay used has the advantage of simplicity. Conclusions-These results indicate that disorders of fatty acid oxidation play a small but significant role in the cause of unexpected death in infants and young children, and that infants and children dying in this way should be regarded as high risk candidates for metabolic dis- eases. (_ Clin Pathol: Mol Pathol 1997;50:212-217) Keywords: children; diagnosis; fatty acid oxidation dis- orders In recent years the number of enzyme deficien- cies in the fatty acid oxidation pathway recognised as giving rise to clinical disease has increased considerably. At least 14 disorders are now described,' most of which are known to be responsible for cases of sudden and unexpected death in infancy."' Medium chain acyl CoA dehydrogenase (MCAD) deficiency is the most common fatty acid oxidation disor- der and is inherited in an autosomal recessive mode. The disorder is caused by mutations in the MCAD gene located on chromosome 1. One prevalent mutation (G985)8 constitutes 90% of mutant alleles in diagnosed patients.9 In the majority of diagnosed cases, the disease presents in infancy with hypoketotic hypogly- caemia and lethargy and is fatal in about 40% of cases, most often with the child dying during the first attack.2 10 Acute episodes are treated effectively with glucose, and long term therapy with frequent meals seems to prevent acute attacks. In northern Europe, the USA, and Australia the carrier frequency of the G985 point mutation is about one in 100 newborns. "-" This is much higher than expected from the number of cases actually diagnosed in these countries, and it is esti- mated that in general only 10-20% of geneti- cally disposed individuals are diagnosed. '4 In Denmark, two new cases are expected each year, but only 10 cases have actually been diag- nosed during the 20 year period since the first case of MCAD deficiency was identified. 15 This might be explained partly by poor diagnostic efficiency and misdiagnoses. However, it is well known that asymptomatic but genotypically affected siblings of patients with MCAD deficiency exist.'6 It seems likely that geneti- cally defined MCAD deficiency is, in many cases, a condition that does not result in a seri- ous clinical disease and, therefore, is not diag- nosed. On the other hand several patients are known to have died in the first months of life due to MCAD deficiency,6 1718 and "missing cases" might also be hidden in this group. A number of cases of MCAD deficiency who died during the first months of life have been misdiagnosed as SIDS.5 6 Therefore, previ- ously, we investigated 120 well defined cases of SIDS (who died from 1 January 1987 to 31 December 1988) to detect the most common disease causing point mutation in the MCAD gene (G985). We used a highly specific polymerase chain reaction (PCR) assay applied to Guthrie blood spots.'0 In this strictly defined population we did not find over-representation of either homozygosity or heterozygosity for G985 compared with the frequency in the gen- eral population." Similar results have been found by other researchers."'2 Institute of Forensic Medicine, University of Aarhus, Finsensgade 15, 8000 Aarhus C, Denmark J B Lundemose M Gregersen Institute of Human Genetics S Kolvraa Center for Medical Molecular Biology, Aarhus University Hospital and Faculty of Health Sciences, Skejby Sygehus 8200 Aarhus N, Denmark N Gregersen Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark E Christensen Correspondence to: Dr Lundemose. Accepted for publication 29 May 1997 212 on June 7, 2020 by guest. Protected by copyright. http://mp.bmj.com/ Mol Path: first published as 10.1136/mp.50.4.212 on 1 August 1997. Downloaded from