Browsing by Author "Cardoso, M.L."
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- Clinical, biochemical and molecular characterization of cystinuria in a cohort of 12 patients.Publication . Barbosa, M.; Lopes, A.; Mota, C.; Martins, E.; Oliveira, J.; Alves, S.; De Bonis, P.; Mota, M. do C.; Dias, Carlos Matias; Rodrigues-Santos, P.; Fortuna, A.M.; Quelhas, D.; Lacerda, L.; Bisceglia, L.; Cardoso, M.L.Cystinuria is a rare autosomal inherited disorder characterized by impaired transport of cystine and dibasic aminoacids in the proximal renal tubule. Classically, Cystinuria is classified as type I (silent heterozygotes) and non-type I (heterozygotes with urinary hyperexcretion of cystine). Molecularly, Cystinuria is classified as type A (mutations on SLC3A1 gene) and type B (mutations on SLC7A9 gene). The goal of this study is to provide a comprehensive clinical, biochemical and molecular characterization of a cohort of 12 Portuguese patients affected with Cystinuria in order to provide insight into genotype–phenotype correlations. We describe seven type I and five non-type I patients. Regarding the molecular classification, seven patients were type A and five were type B. In SLC3A1 gene, two large genomic rearrangements and 13 sequence variants, including four new variants c.611-2A>C; c.1136+44G>A; c.1597T (p.Y533N); c.*70A>G, were found. One large genomic rearrangement was found in SLC7A9 gene as well as 24 sequence variants including 3 novel variants: c.216C>T (p.C72C), c.1119G>A (p.S373S) and c.*82C>T. In our cohort the most frequent pathogenic mutations were: large rearrangements (33.3% of mutant alleles) and a missense mutation c.1400T>C ( p.M467T) (11.1%). This report expands the spectrum of SLC3A1 and SLC7A9 mutations and provides guidance in the clinical implementation of molecular assays in routine genetic counseling of Portuguese patients affected with Cystinuria.
- Liver transplantation prevents progressive neurological impairment in argininemiaPublication . Silva, E.S.; Cardoso, M.L.; Vilarinho, L.; Medina, M.; Barbot, C.; Martins, E.Argininemia is a rare hereditary disease due to a deficiency of hepatic arginase, which is the last enzyme of the urea cycle and hydrolyzes arginine to ornithine and urea. The onset of the disease is usually in childhood, and clinical manifestations include progressive spastic paraparesis and mental retardation. Liver involvement is less frequent and usually not as severe as observed in other UCDs. For this reason, and because usually there is a major neurological disease at diagnosis, patients with argininemia are rarely considered as candidates for OLT despite its capacity to replace the deficient enzyme by an active one. We report on long-term follow-up of two patients with argininemia. Patient 1 was diagnosed by the age of 20 months and despite appropriate conventional treatment progressed to spastic paraparesis with marked limp. OLT was performed at10 years of age with normalization of plasmatic arginine levels and guanidino compounds. Ten years post-OLT, under free diet, there is no progression of neurological lesions. The second patient (previously reported by our group) was diagnosed at 2 months of age, during a neonatal cholestasis workup study. OLT was performed at the age of 7 years, due to liver cirrhosis with portal hypertension, in the absence of neurological lesions and an almost-normal brain MRI. After OLT, under free diet, there was normalization of plasmatic arginine levels and guanidino compounds. Twelve years post-OLT, she presents a normal neurological exami- nation. We conclude that OLT prevents progressive neuro- logical impairment in argininemia and should be considered when appropriate conventional treatment fails.
- Roadmap for implementation of genomics in healthcare: towards equity in access to genomicsPublication . Lopes, M.F.; Costa, A.; Cardoso, M.L.; Custers, I.; Merchant, A.; Konopko, M.; Scollen, S.; Vicente, A. M.As atividades do WP5 do projeto B1MG resultaram num documento intitulado "A Roadmap for genomics in healthcare", que se constitui como um guia e suporte para os sistemas de saúde que pretendam implementar a genómica nos cuidados de saúde, facilitando a utilização do Maturity Level Model e providenciando acesso a guidelines e documentos desenvolvidos no âmbito de outras iniciativas de medicina personalisada. Este poster apresenta o contexto, as atividades e os pontos essenciais que constituem o roadmap.