Rhabdomyolysis andacuteencephalopathy inlate onsetmediumchain acyl-CoA dehydrogenase deficiency

A previously asymptomatic 30year old man presentedwith rhabdomyolysis, muscleweakness, and acuteencephalopathyafter strenuousexertion inthecold without adequate foodintake. Serumand musclecarnitine concentrations were decreased. Urinary excretion ofcarnitine and glycineesters and biochemical examinationof skeletal muscle and fibroblasts ledtothediagnosis ofmedium chainacyl-CoAdehydrogenase (MCAD) deficiency. A point mutation at nucleotide position 985ofthecoding region oftheMCAD gene was found.The MCAD protein was synthesised in the patient's fibroblasts ata normalrate,but was unstable. In general, patients in whom the985pointmutationhasbeen established showmuch more severe clinicalsymptoms andothersymptoms than those seen inthispatient. Therelation of the985pointmutationandtheresidual MCAD activity tothesymptoms isnotas straightforward as previously thought.