Affiliations: Villa Metabolica, Department of Pediatric and Adolescent Medicine, University Medical Center, Mainz, Germany
Note:  Corresponding author: Dr. Julia B. Hennermann, Department of Pediatric and Adolescent Medicine, University Medical Center Mainz Villa Metabolica, Langenbeckstr. 1, 55131 Mainz, Germany. Tel.: +49 6131175754; Fax: +49 6131175672; E-mail: [email protected]
Abstract: Nonketotic hyperglycinemia (NKH) is an autosomal recessive inborn error in the glycine degradation pathway resulting in severe neurological impairment with intractable seizures and brain damage in the majority of the affected patients. Depending on the age of onset and on the outcome of the disease, severe and attenuated forms of NKH may be discriminated. During neonatal period, patients may present with early myoclonic encephalopathy; in the course of the disease, the picture of seizures changes, and multiple forms of seizures may occur. In patients with severe NKH, seizures remain persistent and resistant to anticonvulsant treatment. Variant NKH, caused by mutations resulting in a deficiency of the cofactor lipoate, may lead to a clinical picture resembling severe NKH. Therapy of NKH is directed at decreasing glycine concentrations and at blocking the effect of glycine at the neurotransmitter receptors. Additionally, combined anticonvulsive treatment is necessary in most children with NKH, mainly in those with severe NKH. A few anticonvulsants have shown to be partial effective in patients with NKH. However, all reports on anticonvulsive treatment in NKH are single case reports and no long-term studies have been performed in this patient's cohort. Hence, no recommendations for the treatment of epilepsy in NKH are yet available.