Decline of Acute Encephalopathic Crises in Children with Glutaryl-CoA Dehydrogenase Deficiency Identified by Newborn Screening in Germany

Abstract

Glutaryl-CoA dehydrogenase (GCDH) deficiency is a rare neurometabolic disorder that is considered treatable if patients are identified before the onset of acute encephalopathic crises. To allow early identification of affected individuals, tandem mass spectrometrybased newborn screening for GCDH deficiency has been started in Germany in 1999. We prospectively followed neonatally screened pa-

Glutaric Acidemia Type 1-Clinico-Molecular Profile and Novel Mutations in GCDH Gene in Indian Patients

“…This mutation constituted about 23.5% of all the mutant alleles followed by His403Tyr (alleles frequency 4/ 34, 11.76%). Both these mutations were seen in unrelated families and did not have a similar phenotypic effect, suggesting a poor genotype-phenotype correlation and interfamilial variability in GA I. Intrafamilial variability as previously reported by Gregersen et al (1977) and Kolker et al (2007) was also observed in one of our families; the siblings in F10 and F11 (F10 showed presence of isolated macrocephaly and seizure in one sib and severe dystonia with regression in another sib) with the same mutation and genetic background had different phenotypes, suggesting intrafamilial variability in GA I. This intrafamilial and interfamilial variability can probably be explained by the epigenetic factors or complex interactions at tissue or metabolic levels and the extent of neurological damage caused by the various precipitating factors (Wang et al 2013).…”

“…Hence no emergency regimen was given at the time of acute precipitating factors. However, after initial diagnosis, patients were explained about emergency home treatment (Kolker et al 2006(Kolker et al , 2007(Kolker et al , 2011). An individualized long-term dietary treatment (Kolker et al 2011;Viau et al 2012;Lee et al 2013) includes a low lysine diet through natural protein with or without lysinefree and tryptophan-reduced amino acid supplements along with L-carnitine supplementation for adequate growth (Boy et al 2013).…”

“…Extrapyramidal symptoms are due to bilateral striatal injury during the acute episode. Early diagnosis and prompt initiation of treatment can prevent the long-term complications and mortality which have led to its inclusion in conservative newborn screening programs (Heringer et al 2010;Kolker et al 2007). GCDH enzyme is encoded by GCDH gene, which is located on the chromosome 19p13.2 spanning about~7 kb and contains 12 exons (Transcript ID ENST00000222214) and encodes 438 amino acid-long precursor protein.…”

Newborn Screening Programmes in Europe, Arguments and Efforts Regarding Harmonisation: Focus on Organic Acidurias

“…NBS and subsequent treatment of GA-I according to an international guideline have significantly improved the neurological outcome of affected individuals (Heringer et al 2010;K€ olker et al 2006, 2007, and NBS is considered a cost-effective diagnostic strategy for countries with healthcare systems comparable to Germany (Pfeil et al 2013). According to this international guideline, it is crucial to start treatment early before the manifestation of irreversible neurologic damage (K€ olker et al 2011).…”

Perioperative Management of a Patient With Glutaric Aciduria

“…The disorder generally presents in early childhood with the majority of children having no measurable enzyme activity. The estimated prevalence varies from 1 in 30,000 newborns in one Scandinavian study to 1 in 30,000 -100,000 newborns in other studies [2][3][4][5]. The prevalence may be much higher in isolated populations in the Middle East countries due to higher rates of consanguinity [6,7].…”