Ethylmalonic encephalopathy (EE) is an inherited error of metabolism (IEM) characterized by elevated excretion of ethylmalonic acid, and affects on several body systems, including the circulatory and gastrointestinal systems, but particularly the nervous system. The neurological features of the disease include progressive neurodevelopmental delay, hypotonia, seizures, and psychomotor regression. Abnormalities may also be visible on brain scans. Other symptoms of the condition include the appearance of recurrent petechia, cyanosis in the hands and feet, and chronic diarrhea. These clinical features may be present at birth, or develop within the first few months. The metabolic picture is that of elevated urinary excretion of ethylmalonic acid, along with methylsuccinic acid, and acylglycines.
EE is a rare disorder, with only about 40 patients having been reported worldwide. Most of these patients originate from the Mediterranean and/or Arab region. Diagnosis is based on the clinical symptoms, and biochemical analysis, although a genetic analysis is required for confirmation. The urinary and serum metabolite profile in EE can resemble that seen in multiple acyl-coA dehydrogenase deficiency or short chain acyl-coA dehydrogenase deficiency. However, the clinical profile of petechia, acrocyanosis and diarrhea is quite unique for EE. Management of the condition involves treatment with L-carnitine, riboflavin, and/or Q10 supplements. However, the prognosis for the condition is generally poor. The neurological problems typically worsen, and most affected patients do not survive beyond childhood.