Characterization of novel GCDH pathogenic variants causing glutaric aciduria type 1 in the southeast of Mexico

Publication date: December 2019Source: Molecular Genetics and Metabolism Reports, Volume 21Author(s): Felix-Julian Campos-Garcia, Oscar F. Chacon-Camacho, Silvina Contreras-Capetillo, Marisa Cruz-Aguilar, Carolina E. Medina-Escobedo, Claudia M. Moreno-Graciano, Agustín Rodas, Luz del Alba Herrera-Perez, Juan C. ZentenoAbstractBiallelic mutations of the GCDH gene result in Glutaric Aciduria type 1 (GA1; OMIM #231670), an uncommon autosomal recessive inborn error caused by the deficiency of glutaryl-CoA dehydrogenase (CCDH), a mitochondrial matrix protein involved in the degradation of l-lysine, L-hydroxylysine, and L-tryptophan. The enzymatic deficiency leads to the accumulation of neurotoxins causing macrocephaly at birth, hypotonia and dystonia due to bilateral striatal injury, that evolves with aging, if untreated, to fixed dystonia and akinetic-rigid parkinsonism. In this article, we describe the results of molecular studies of 5 unrelated patients with GA1 in Southern Mexico. Mutational analysis identified 2 novel likely pathogenic GCDH variants (p.Leu130Pro and p.Gly391Val), 1 pathogenic variant that is predicted to cause a premature stop codon (p.Leu370*), and 2 previously reported pathogenic variants (p.Arg294Trp and p.Arg294Gln). The recurrence of the p.Leu130Pro variant (60% of mutant alleles) suggested a possible founder mutation effect. Our results expand the mutational spectrum in GA1 patients and support the importance of early diagnosis through newborn sc...
Source: Molecular Genetics and Metabolism Reports - Category: Genetics & Stem Cells Source Type: research

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Source: Neurology Clinical Practice - Category: Neurology Authors: Tags: Dystonia, Basal ganglia Case Source Type: research
During a hospitalization for sepsis in the setting of a urinary tract infection, a 69-year-old man with idiopathic Parkinson disease (PD) developed severe, sudden-onset left-sided neck pain an hour after receiving quetiapine to treat hospital delirium, raising concern for acute dystonic reaction. On review of the patient's history, he had received single doses of haloperidol and quetiapine 1 week and 3 days prior, respectively, without documented dystonic reaction. He had a history of dystonia in his right foot, which was well controlled with botulinum toxin injections. On examination, his head was rotated toward the right...
Source: Neurology Clinical Practice - Category: Neurology Authors: Tags: Clinical neurology examination, All Movement Disorders, Dystonia, Parkinson's disease/Parkinsonism, Botulinum toxin Case Source Type: research
Publication date: Available online 7 December 2019Source: Drug Discovery Today: Disease ModelsAuthor(s): Vanna Micheli, Gabriella Jacomelli, Annalisa Santucci, Giulia BernardiniLesch–Nyhan Disease (LND) is a rare X-linked recessive metabolic and neurological syndrome due to the deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT). Peculiar neurological symptoms occur in LND: dystonia, choreoathetosis, compulsive self-injurious behaviour, with no obvious correlation to the deficiency of this purine salvage anzyme. A dopaminergic deficit was found to underlie the neurologic symptoms, but the aetiology fo...
Source: Drug Discovery Today: Disease Models - Category: Drugs & Pharmacology Source Type: research
A 24-year-old woman with an unresectable right mesencephalic pilocytic astrocytoma was treated with stereotaxic radiation therapy. Three months after a radiation therapy–induced bleeding, she presented a severe disabling low frequency rest and kinetic tremor involving the left upper limb, associated with dystonia, and a Holmes tremor was suspected. Thereby, we performed a 123I-FP-CIT SPECT (DATSCAN) that revealed a normal distribution of radiotracer over the left striatum, whereas no binding was seen in the right caudate and putamen. This pattern was consistent with a right severe nigrostriatal dopaminergic denervati...
Source: Clinical Nuclear Medicine - Category: Nuclear Medicine Tags: Interesting Images Source Type: research
CONCLUSIONS: Genetic analysis along with thorough clinical analysis supported by radiological findings will aid the differential diagnosis of MPAN within the neurodegeneration with brain iron accumulation spectrum as well as other disorders including hereditary spastic paraplegia. Dystonia and parkinsonism may not be the leading clinical findings in MPAN patients, as these are absent in the atypical case. Finally, we emphasise that the existence of frameshifting variants may bias the age of onset toward childhood. PMID: 31804703 [PubMed - as supplied by publisher]
Source: Neurologia i Neurochirurgia Polska - Category: Neurology Authors: Tags: Neurol Neurochir Pol Source Type: research
Fine motor control of not only muscle contraction but also muscle relaxation is required for appropriate movements in both daily life and sports. Movement disorders such as Parkinson’s disease and dystonia are often characterized by deficits of muscle relaxation. Neuroimaging and neurophysiological studies suggest that muscle relaxation is an active process requiring cortical activation, and not just the cessation of contraction. In this article, we review the neural mechanisms of muscle relaxation, primarily utilizing research involving transcranial magnetic stimulation (TMS). Several studies utilizing single-pulse ...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Abstract GLUT1 deficiency is a rare neurometabolic disorder that can be effectively treated with ketogenic diet. However, this condition is underdiagnosed due to its nonspecific, overlapping, and evolving symptoms with age. We retrospectively reviewed the clinical course of nine patients diagnosed with GLUT1 deficiency, based on SLC2A1 mutations and/or glucose concentration in cerebrospinal fluid. The patients included eight boys and one girl who initially presented with seizures (44%, 4/9) or delayed development (44%, 4/9) before 2 years of age, except for one patient who presented with apnea as a neonate. Over t...
Source: Yonsei Medical Journal - Category: Universities & Medical Training Authors: Tags: Yonsei Med J Source Type: research
Conclusion: Translation, cultural adaptation and validation of the MoCA to Hiligaynon was successfully done. This tool may now be used in clinical practice and in research for Hiligaynon-speaking subjects.
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Publication date: 2019Source: International Review of Neurobiology, Volume 149Author(s): Alessio Di Fonzo, Giulia Franco, Paolo Barone, Roberto ErroAbstractIf the presence of dystonia is a well-recognized phenomenon in disorders predominantly presenting with parkinsonism, including sporadic Parkinson Disease, the term dystonia-parkinsonism usually refers to rare conditions, often genetic, in which the severity of dystonia usually equates that of parkinsonism. At variance with parkinsonian syndromes with additional dystonia, the conditions reviewed in this chapter have usually their onset in childhood and their diagnostic w...
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
Publication date: 2019Source: International Review of Neurobiology, Volume 149Author(s): Anne Weissbach, Christina Wittke, Meike Kasten, Christine KleinAbstractGenetic atypical Parkinson's disease (PD) describes monogenic forms of PD that resemble idiopathic PD but feature prominent atypical clinical signs and symptoms and can be sub-grouped into i) atypical monogenic forms caused by mutations in the ATP13A2, DNAJC6, FBXO7, SYNJ1, VPS13C, and DCTN genes; ii) monogenic PD more closely resembling idiopathic PD, but associated with atypical features in at least a subset of cases (SNCA-, LRRK2-, VPS35-, Parkin-, PINK1-, and DJ...
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
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