Diagnosis of glycine encephalopathy in a pediatric patient by detection of a GLDC mutation during initial next generation DNA sequencing

Abstract

Early diagnosis for metabolic encephalopathy caused by inborn errors of metabolism is very important for the initiation of early treatment and also for prevention of sequela. Metabolic encephalopathy in the form of seizures can result from many inborn errors of metabolism and considering the large number of disorders causing metabolic encephalopathy, enzyme assays or conventional molecular tests are expensive and take considerably long period of time which results in delayed treatment. In our center we have used next generation DNA sequencing technology as an initial diagnostic test to look for about 700 disorders at the same time for the etiologic diagnosis of a 4-month-old female infant suffering from intractable seizures. The patient was found to have glycine encephalopathy resulting from a previously defined mutation in the GLDC gene. The diagnostic result was obtained much sooner than other conventional investigations. Up to our knowledge, this would be the first case with glycine encephalopathy in the literature who was approached by this novel panel method initially. Although currently, classical evaluation methods such as physical examination, biochemical and conventional molecular investigations are still accepted as the gold standards to clarify the etiology of the metabolic encephalopathy it is obvious that next generation sequence analysis will play a very significant role in the future.

Novel homozygous GLDC variant causing late-onset glycine encephalopathy: A case report and updated review of the literature

“…Brain MRI often shows thin and shortened corpus callosum, hydrocephalus, cerebral atrophy, ventricular dilatation, hypomyelination [ 1 ]. Most of patients with glycine encephalopathy have an uneventful pregnancy with normal delivery ( Supplementary Table S1 ) [ [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] ]. Here, we document an 8-year-old-boy with late-onset nonketotic hyperglycinemia (NKH) in whom WES revealed a novel homozygous GLDC likely pathogenic variant c.707G > A p.(Arg236Gln).…”