Atypical Glutaric Aciduria Type I with Hemidystonia and Asymmetric Radiological Findings Misdiagnosed as an Ischemic Stroke

Demailly, Diane; Vianey‐Saban, Christine; Acquaviva, Cécile; González, Victoria; Rubio, I. De Antonio; Cyprien, Fabienne; Roujeau, Thomas; Masoliver, Adria; Leboucq, Nicolas; Coubes, Philippe; Cif, Laura

doi:10.1002/mdc3.12633

Cited by 6 publications

(7 citation statements)

References 9 publications

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“…A systematic literature search was performed by the authors and conducted in PubMed for publications between January 2000 up to May 2022, that report GCDH variants in GA1 patients. For this search the following MeSH terms were used: “glutaric aciduria type 1,” “glutaric acidemia type 1,” “glutaric aciduria type I,” “glutaric acidemia type I,” “glutaryl‐CoA dehydrogenase deficiency,” and “GCDH” 30–107 . References from selected articles from before the year 2000 with complete description of GA1 patients were also included.…”

Section: Methodsmentioning

confidence: 99%

Exploring genotype–phenotype correlations in glutaric aciduria type 1

Schuurmans

Dimitrov

Schröter

et al. 2023

J of Inher Metab Disea

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Glutaric aciduria type 1 (GA1) is a rare neurometabolic disease caused by pathogenic variants in the gene encoding the enzyme glutaryl-CoA dehydrogenase (GCDH). We performed an extensive literature search to collect data on GA1 patients, together with unpublished cases, to provide an up-to-date genetic landscape of GCDH pathogenic variants and to investigate potential genotypephenotype correlation, as this is still poorly understood. From this search, 421 different GCDH pathogenic variants have been identified, including four novel variants; c.179T>C (p.Leu60Pro), c.214C>T (p.Arg72Cys), c.309G>C (p.Leu103Phe), and c.665T>C (p.Phe222Ser).The variants are mostly distributed across the entire gene; although variant frequency in GA1 patients is relatively high in the regions encoding for active domains of GCDH. To investigate potential genotype-phenotype correlations, phenotypic descriptions of 532 patients

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Section: Methodsmentioning

confidence: 99%

Exploring genotype–phenotype correlations in glutaric aciduria type 1

Schuurmans

Dimitrov

Schröter

et al. 2023

J of Inher Metab Disea

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“…Data on long‐term outcome after pallidotomy are not available. Bilateral deep brain stimulation of the internal globus pallidum reduced dystonia and slightly improved motor function in one patient 181 while minor improvement was also observed in a patient with atypical hemi‐dystonia due to unilateral striatal necrosis after acute encephalopathic crisis 32 . However, no effect was detected in another patient with classical, severe acute‐onset MD ( personal communication Dr .…”

Section: Neurologic Complicationsmentioning

confidence: 97%

“…Bilateral deep brain stimulation of the internal globus pallidum reduced dystonia and slightly improved motor function in one patient 181 while minor improvement was also observed in a patient with atypical hemi-dystonia due to unilateral striatal necrosis after acute encephalopathic crisis. 32 However, no effect was detected in another patient with classical, severe acute-onset MD (personal communication Dr. Cif, Montpellier). Although positive effects on pain scale were reported, 182 disparate motor outcome with slight improvement but also decline after deep brain stimulation was observed in patients with heredodegenerative dystonia including two GA1 patients.…”

Section: Neurosurgerymentioning

confidence: 98%

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Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: Third revision

Boy

Mühlhausen²,

Maier

et al. 2022

J of Inher Metab Disea

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Glutaric aciduria type 1 is a rare inherited neurometabolic disorder of lysine metabolism caused by pathogenic gene variations in GCDH (cytogenic location: 19p13.13), resulting in deficiency of mitochondrial glutaryl-CoA dehydrogenase (GCDH) and, consequently, accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid and glutarylcarnitine detectable by gas chromatography/mass spectrometry (organic acids) and tandem mass spectrometry (acylcarnitines). Depending on residual GCDH activity, biochemical high and low excreting phenotypes have been defined. Most untreated individuals present with acute onset of striatal damage before age 3 (to 6) years, precipitated by infectious diseases, fever or surgery, resulting in irreversible, mostly dystonic movement disorder with limited life expectancy. In some patients, striatal damage develops insidiously. In recent years, the clinical phenotype has been extended by the finding of extrastriatal abnormalities and cognitive dysfunction, preferably in the high excreter group, as well as chronic kidney failure. Newborn screening is the prerequisite for pre-symptomatic start of metabolic treatment with low lysine diet, carnitine supplementation and For affiliation refer to page 29

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“…This phenomenon of subdural effusion requiring surgical drainage has been infrequently reported. 2,26 Nine patients died from their complications during the period of study (►Table 1). Two patients from our study have been published separately as case reports (case 1: Kamate et al 27 ; case 19: Vasikarla et al 28 ).…”

Section: Journal Of Pediatric Geneticsmentioning

confidence: 99%

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

et al. 2020

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Glutaric 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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Atypical Glutaric Aciduria Type I with Hemidystonia and Asymmetric Radiological Findings Misdiagnosed as an Ischemic Stroke

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Cited by 6 publications

References 9 publications

Exploring genotype–phenotype correlations in glutaric aciduria type 1

Exploring genotype–phenotype correlations in glutaric aciduria type 1

Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: Third revision

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

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