Guideline for the diagnosis and management of glutaryl‐CoA dehydrogenase deficiency (glutaric aciduria type I)

Abstract

Glutaryl-CoA dehydrogenase (GCDH) deficiency is an autosomal recessive disease with an estimated overall prevalence of 1 in 100 000 newborns. Biochemically, the disease is characterized by accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine, which can be detected by gas chromatography-mass spectrometry of organic acids or tandem mass spectrometry of acylcarnitines. Clinically, the disease course is usually determined by acute encephalopathic crises precipitated by infectious diseases, immunizations, and surgery during infancy or childhood. The characteristic neurological sequel is acute striatal injury and, subsequently, dystonia. During the last three decades attempts have been made to establish and optimize therapy for GCDH deficiency. Maintenance treatment consisting of a diet combined with oral supplementation of L: -carnitine, and an intensified emergency treatment during acute episodes of intercurrent illness have been applied to the majority of patients. This treatment strategy has significantly reduced the frequency of acute encephalopathic crises in early-diagnosed patients. Therefore, GCDH deficiency is now considered to be a treatable condition. However, significant differences exist in the diagnostic procedure and management of affected patients so that there is a wide variation of the outcome, in particular of pre-symptomatically diagnosed patients. At this time of rapid expansion of neonatal screening for GCDH deficiency, the major aim of this guideline is to re-assess the common practice and to formulate recommendations for diagnosis and management of GCDH deficiency based on the best available evidence.

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

“…In conclusion, the present study demonstrates that NBS in combination with intensive management reduces the risk for the onset of prognostically relevant acute encephalopathic crises in the majority of children with GCDH deficiency and thus confirms recent recommendations for the diagnosis and management of this disease (18). This guideline also describes in detail how maintenance and emergency treatment can be applied.…”

Networking Across Borders for Individuals with Organic Acidurias and Urea Cycle Disorders: The E-IMD Consortium

“…In some countries these diseases are included in newborn screening programmes, hereby allowing early detection and start of treatment in asymptomatic individuals. This early intervention hopefully leads to improved health outcome, as it has been shown for glutaric aciduria type 1 (GA-1) and isovaleric aciduria (IVA) (Gr€ unert et al 2012;Heringer et al 2010;K€ olker et al 2007a). …”

GAI – distinct genotype and phenotype characteristics in reported Slovak patients

“…GAI is a treatable disorder and the guidelines for the GAI management were published by Kölker et al (16) and afterwards summarised by Heringer et al (21). Appropriate therapeutic recommendations can prevent the movement disorder and irreversible cerebral damage in GAI patients identifi ed especially by NBS.…”

“…The fi rst clinical manifestation of the disease may occur as an acute encephalopathic episode triggered by infection, immunisation or surgical intervention and leads to the sudden onset of hypotonia and loss of head control as a fi rst indicator of GAI (16). In undiagnosed and untreated patients, the neurological impairment can develop in age of 3-36 months of life.…”