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DOI: 10.1055/s-2008-1079541
A severe case of encephalopathy with ethylmalonic aciduria and generalized vasculopathy
Ethylmalonic Encephalopathy (EE) is a rare autosomal recessive metabolic disorder presumably restricted to the Mediterranean region caused by mutations in the ETHE-1 gene on chromosome 19q13. EE is characterized by clinical features including psychomotor retardation, hypotonia, petechiae, acrocyanosis, as well as a typical metabolic profile in body fluids and a typical neuroradiologic pattern. Despite the identification of the underlying gene defect the pathomechanism of EE is only partly understood. ETH1 enzyme is localised in the mitochondrial matrix, the substrate(s) are still unknown.
We describe a 12-month old male who presented with severe psychomotor retardation, profound muscle hypotonia, epileptic seizures, relapsing petechiae, acrocyanosis and peripheral edema. Lactate was significantly elevated in the blood and CSF, and urinary organic acid analysis showed an extremly high excretion of ethylmalonic acid. Brain MRI revealed atrophy in the fronto-temporal areas as well as involvement of the basal ganglia and brain stem. EEG showed hypsarrythmia. In the course of the disease the patient developed a pharmacoresistant nephrotic syndrome which led to anasarka, lung edema and finally cardiac and respiratory failure at the age of 13 month. A high dose of riboflavine did not show any significant effect.
Results of genetic analysis and fibroblast cultures are still due. Differential diagnosis includes SCAD deficiency, multiple acyl-CoA dehydrogenase deficiency and mitochondrial respiratory chain dysfunction.