Three Children with Alpers' syndrome 2007–2010

Introduction: Alpers-Syndrome (psychomotor retardation, intractable epilepsy, and liver failure) is a very rare disorder with an incidence of 1:100.000–1:250.000. Alpers-Syndrome is caused by mutation in the nuclear gene encoding mitochondrial DNA polymerase γ (POLG-1, Chromosome 15q25). In most cases patients become symptomatic before age 2 years. We report three patients, which were treated between 2007–2010. Patients: 1. Our first patient showed a mild muscular hypotonia at the age of 6 months, at age 12 months she had a mild psychomotor retardation and developed a refractory convulsive status. Afterwards she had severe myoclonic seizures and a rapidly progressive dementia. Repeatedly she suffered from severe vomiting and bowel obstruction. She died at age 34 months. 2. Our second patient showed a mild psychomotor retardation and ataxia at age 15 months. At the same time he developed a convulsive status, which was successfully treated with midazolam. Afterwards he suffered from myoclonic seizures. At the age of 21 months he developed a refractory convulsive seizure and a rapidly progressive dementia. He had repeated episodes of vomiting and bowel obstruction. He died at age 23 months. 3. Our third patient showed a mild psychomotor retardation and mild ataxia at age 12 months. The ataxia worsened over time and development was stationary after her second birthday. At the age of 42 months she developed a refractory convulsive status. Afterwards she had severe myoclonic seizures. After a short interval of improvement she developed a rapidly progressive dementia. After suffering from Rotavirus positive gastroenteritis she had persistent gastrointestinal problems with finally a bowel obstruction. The patient died at age 46 months. All patients had heterozygous mutations in POLG-1, which have been reported in association with Alpers-Syndrome before or were in an enzymatic region where mutations are believed to be clinically relevant. All patients suffered from myoclonic seizures and had at least one refractory convulsive status. Gastrointestinal problems were severe in all patients despite only mildly deranged liver function. EEG and MRI of all patients will be discussed.