Browsing by Author "Diogo, Luisa"
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- Biochemical data as important clues for diagnosis of SUCLA2 defectsPublication . Nogueira, Célia; Garcia, Paula; Diogo, Luisa; Valongo, Carla; Santorelli, Filippo; Vilarinho, Laura
- Identification of novel L2HGDH gene mutations and update of the pathological spectrumPublication . Vilarinho, Laura; Tafulo, Sandra; Sibilio, Michelina; Kok, Fernando; Fontana, Federica; Diogo, Luisa; Venâncio, Margarida; Ferreira, Mariana; Nogueira, Celia; Valongo, Carla; Parenti, Giancarlo; Amorim, António; Azevedo, LuisaL-2-hydroxyglutaric aciduria (L-2-HGA, MIM 236792) is a neurometabolic disorder caused by the toxic accumulation of high concentration of L-2-hydroxyglutaric acid in plasma and cerebrospinal fluid. Distinct mutations on the L2HGDH gene have been associated with the clinical and biochemical phenotype. Here we present three novel mutations (Gln197X, Gly211Val and c.540+1 G4A), which increase the present deleterious collection of L2HGDH gene up to 35 mutations that we have compiled in this study. In addition, we used the haplotypic information based on polymorphic markers to demonstrate the common origin of Gly57Arg harboring chromosomes.
- A novel missense mutation in SUCLA2 associated with mild methylmalonic aciduriaPublication . Nogueira, Célia; Garcia, Paula; Diogo, Luisa; Valongo, Carla; Santorelli, Filippo; Vilarinho, LauraIntroduction Succinyl CoA synthase is a mitochondrial matrix enzyme that catalyzes the reversible synthesis of succinate and ATP or GTP from succinyl-CoA and ADP in the tricarboxylic acid cycle (TCA). This enzyme is made up of two subunits, α and β, encoded by SUCLG1 and SUCLA2, respectively. The clinical features of patients with mutations in SUCLA2 include early childhood hypotonia, developmental delay, and almost invariably, progressive dystonia and sensorineural deafness. Mutations in SUCLA2 and SUCLG1 cause an encephalomyopathic form of infantile mtDNA depletion syndrome. A useful diagnostic clue in succinyl CoA synthase disorders is a ‘‘mildly’’ elevated urinary methylmalonic acid (MMA), and presence of TCA intermediates. To date, two patients with SUCLG1 mutations have been reported, whereas mutations in SUCLA2 have been reported in 17 patients. We here present an additional patient with a novel SUCLA2 mutation. Methods We report a 17-month-old-boy, who presented severe muscular hypotonia, failure to thrive, developmental delay, weight loss during a gastroenteritis crises, dysmorphisms and muscular atrophy. A clinical investigation disclosed hyperlactacidemia together with moderate excretion of MMA and elevated C4-dicarboxylic carnitine. Sequencing analysis of SUCLA2 and SUCLG1 was performed using standard methods. Results Mutation analysis of SUCLA2 revealed a homozygous c.985A>G mutation in exon 8 (p.M329V). This missense mutation affects an amino acid that is highly conserved in different species and was not found in controls. The analysis by bioinformatics tools also confirmed a pathogenic mutation. Discussion The clinical and biochemical phenotype of our patient is strikingly similar to other reported patients with SUCLA2 mutations. In addition, the mildly elevated levels of methylmalonate and lactate raised the suspicion of this disease. Our study contributed to expand the spectrum of patients with SUCLA2 mutations, and will be important for an accurate genetic counseling and a prenatal diagnosis to the affected family.
- Projet FIND - the first yearPublication . Gaspar, Paulo; alves, sandra; Teles, Elisa Leão; Diogo, Luisa; Vilarinho, LauraThe first year of the project FIND about Lysosomal Storage Disorders.