Abstracts

Up to 30% of children with mental retardation (MR) have epilepsy and up to 45 % of children with epilepsy have MR (Epilepsia. 2000 Sep;41(9):1214-20). The report of the Amalfi group raised concern about missing treatable causes of epilepsy; as a result diagnostic metabolic testing in children with developmental delay and epilepsy is commonly performed . (J Child Neurol. 2002 Dec;17 Suppl 3:3S98-102)
A standardized approach to such testing does not yet exist, and the prevalence of metabolic disease in this population is not known., Records of the 429 children admitted to the pediatric epilepsy monitoring unit during 2005 were reviewed. We noted the presence or absence of developmental delay, type of EEG discharges (focal-mixed or generalized), and presence or absence of metabolic testing. Metabolic studies included : a) Plasma amino acids, biotinidase, lactate/pyruvate, acylcarnitines, ammonia levels, transferring isoelectric focusing, peroxisomal testing, and uric acid; b) CSF amino acids, glucose and lactate/pyruvate levels; and c) Urine organic acids, uric acid and creatine/guanidinoacetate levels., 20% of our patients received some metabolic testing (85/429). Metabolic abnormalities were found in 48% of these patients (40/83), with 31% of these individuals having findings of mitochondrial dysfunction (27/85) with elevations in a) plasma alanine/proline/sarcosine (amino acids); b) plasma lactic acid; and c) urine lactic acid, 3-methyl-glutaconic acid and Kreb cycle intermediates (organic acids). Metabolic abnormalities were most common in those with focal discharges (70 %; 21/30), when compared to multi-focal (53%; 8/15) and generalized (40%; 13/32) discharges. Secondary carnitine deficiency (26%, 22/85) and valproate related isolated elevations in plasma glycine (63%, 5/8) were also commonly seen. A single patient with a disorder of creatine metabolism was identified. Only 11% of the patients had CSF analysis done (10/85) with a 30% yield of abnormalities (3/10), including elevations in alanine, glutamate or glutamine. Of 9 patients with seizures but normal development, 6 had metabolic abnormalities identified (66%). Only 17 individuals received their first MRI at our institiution, with 86% (12/14) having structural abnormalities found,, and one of these individuals, with a cortical heterotopia, having mitochondrial disease diagnosed., Metabolic abnormalities may represent a significant finding in individuals with epilepsy, especially in those with developmental delays, even despite findings of a focal structural brain abnormality. A systematic approach to the diagnoses of these individuals is needed. A consult with a metabolic specialist is encouraged in these patients if a diagnosis is not known. Disorders of mitochondrial metabolism should be placed high on the differential list.,