Ethylmalonic encephalopathy: A metabolic disorder masquerading as cerebral palsy

Abstract

Many metabolic disorders may present with similar symptoms and signs as cerebral palsy. Some of these disorders which are slowly progressive are more likely to be misdiagnosed as CP. A 5-years-old boy was born at 40 weeks gestation to unrelated parents. The pregnancy was complicated by anemia and gestosis. The vaginal delivery was uncomplicated. Birth weight was 3360 g, length was 51 cm. APGAR scores were 7 and 8 at 1 and 5 min. Child developed well up to 2,5 months. At 3 months of age he manifested irritability and sleep problems. After 3 months the early developmental milestones were abnormal. Since the age of 6 months he had periodic petechial rash, acrocyanosis and diarrhea. At 1 year old the diagnosis of hypotonic cerebral palsy was made. Instead of permanent rehabilitation child had severe psychomotor dysfunction and development delay. At 5 years of life he developed his first epileptic seizure. The treatment with Levetyracetam was started. At the age of 5 years the patient had development delay and spactic diplegia. According to Gross Motor Function Classification System he has level IV. Due to atypical course of the disease and to the specific symptoms diagnosis of cerebral palsy has been questioned and the child underwent appropriate evaluation. Blood amino acids and acylcarnitines analysis revealed high C4 level. The level of ethylmalonic acid in urine was elevated. Genetic analysis revealed two heterozygous variants in the ETHE1 gene: NM_014297.3: c.487C˃G, p.R163G (CM077533) and NM_014297.3: c. 487C˃T, p.R163W (CM040420). The diagnosis of Ethylmalonic encephalopathy was confirmed. The treatment with N-acetyl-cysteine and metronidazole was started with good effect. Metabolic evaluation should be performed in all children with CP for an underlying cause, particularly in situations when there is a presence of a positive family history of “cerebral palsy”, occurrence of developmental regression, multisystemic involvement.