Glutaric aciduria type 1 in children. Clinical presentation of 46 cases in Russian families

Background. Glutaric aciduria type 1 is an autosomal recessive disease caused by mutations in the GCDH gene, which encodes the enzyme glutaryl‑CoA dehydrogenase. Metabolic crisis in type 1 glutaric aciduria is an acute life‑threatening condition that requires careful diagnosis with a number of other conditions and the immediate initiation of pathogenetic therapy.Materials and methods. Clinical manifestations, neuroimaging characteristics of the disease were studied in 46 patients with diagnosed glutaric aciduria type 1 confirmed by biochemical and molecular genetic methods. Methods: gas chromatography with mass spectrometry, tandem mass spectrometry, Sanger sequencing, chromosomal microarray analysis of the exon level.Results and discussion. A retrospective analysis of anamnestic and clinical data was carried out, and the nature and age of disease manifestation, provoking factors, a spectrum of clinical manifestations and neuroimaging data were assessed.Conclusion. How initiated treatment prevents progression of neurological symptom relief and patient adaptation. With the help of the goal, it is necessary to inform pediatricians, neurologists and neuroradiologists about this feature of the course of glutaric aciduria type 1 in order to increase the clinical alertness of this disease.

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Newborn screening by tandem mass spectrometry for glutaric aciduria type 1: a cost-effectiveness analysis

Orphanet Journal of Rare Diseases ◽

10.1186/1750-1172-8-167 ◽

2013 ◽

Vol 8 (1) ◽

pp. 167 ◽

Cited By ~ 16

Author(s):

Johannes Pfeil ◽

Stefan Listl ◽

Georg F Hoffmann ◽

Stefan Kölker ◽

Martin Lindner ◽

...

Keyword(s):

Mass Spectrometry ◽

Cost Effectiveness ◽

Tandem Mass Spectrometry ◽

Newborn Screening ◽

Glutaric Aciduria Type ◽

Tandem Mass ◽

Glutaric Aciduria Type 1 ◽

Glutaric Aciduria ◽

Effectiveness Analysis

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Clinical Characteristics, Molecular Profile, and Outcomes in Indian Patients with Glutaric Aciduria Type 1

Journal of Pediatric Genetics ◽

10.1055/s-0040-1715528 ◽

2020 ◽

Author(s):

Parag M. Tamhankar ◽

Lakshmi Vasudevan ◽

Pratima Kondurkar ◽

Sarfaraj Niazi ◽

Rita Christopher ◽

...

Keyword(s):

Mass Spectrometry ◽

Genetic Variants ◽

Clinical Characteristics ◽

Glutaric Aciduria Type ◽

Molecular Profile ◽

Glutaric Aciduria Type 1 ◽

Intravenous Glucose ◽

Glutaric Aciduria ◽

The Mean

AbstractGlutaric acidemia type 1 (GA-1, OMIM 231670) is an autosomal recessive inborn error of metabolism caused by the deficiency of glutaryl-coenzyme A (CoA) dehydrogenase with most children presenting in infancy with encephalopathy, dystonia, and macrocephaly. We present the clinical characteristics, molecular profile, and outcomes in 29 unrelated families with affected children (30 cases total). The mean age at onset of illness was 10 months (±14.58), whereas the mean age at referral for molecular diagnosis was 29.44 months (±28.11). Patients were residents of nine different states of India. Clinical presentation varied from acute encephalitis followed by neuroregression and chronic/insidious developmental delay. Neurological sequelae varied from asymptomatic (no sequelae, 2 patients) to moderate (5 patients) and severe (23 patients) sequelae. All patients underwent blood tandem mass spectrometry (TMS on dried blood spots) and/or urine gas chromatography mass spectrometry (GCMS). Neuroimaging demonstrated batwing appearance in 95% cases. Sanger's sequencing of GCDH, covering all exons and exon–intron boundaries, was performed for all patients. Variants identified include 15 novel coding variants: p.Met100Thr, p.Gly107Ser, p.Leu179Val, p.Pro217Ser, p. Phe236Leufs*107, p.Ser255Pro, p.Met266Leufs*2, p.Gln330Ter, p.Thr344Ile, p.Leu345Pro, p.Lys377Arg, p.Leu424Pro, p.Asn373Lys, p.Lys377Arg, p.Asn392Metfs*9, and nine known genetic variants such as p.Arg128Gln, p.Leu179Arg, p.Trp225Ter, p.Met339Val, p.Gly354Ser, p.Arg402Gln, p.Arg402Trp, p.His403Tyr, and p.Ala433Val (Ensembl transcript ID: ENST00000222214). Using in silico analysis, genetic variants were shown to be affecting the residues responsible for homotetramer formation of the glutaryl-CoA dehydrogenase protein. Treatment included oral carnitine, riboflavin, protein-restricted diet, lysine-deficient special formulae, and management of acute crises with intravenous glucose and hydration. However, the mortality (9/30, 27.58%) and morbidity was high in our cohort with only two patients affording the diet. Our study is the largest multicentric, genetic variant–proven series of glutaric aciduria type 1 from India till date.

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