Os autores apresentam o caso de um recem-nascido do sexo masculino com hipotonia severa, succao d... more Os autores apresentam o caso de um recem-nascido do sexo masculino com hipotonia severa, succao debil, convulsoes, facies dismorfico ehepatomegalia. Esttidos subsequentes revelaram, leucodistrofia, disfuncao hepatica, aumento dos acidos gordos de cadeia muito longa (AGCML) ediminuicao da actividade enzimatica da dihidroxiacetonafosfato-aciltransferase (DHAP-AT) nos fibroblastos. Os resultados laboratoriais e a evolucaoclinica apoiam o diagnostico de Sindroma de Zellweger.
PURPOSE Prolidase deficiency is a rare inborn error of metabolism causing ulcers and other skin d... more PURPOSE Prolidase deficiency is a rare inborn error of metabolism causing ulcers and other skin disorders, splenomegaly, developmental delay, and recurrent infections. Most of the literature is constituted of isolated case reports. We aim to provide a quantitative description of the natural history of the condition by describing 19 affected individuals and reviewing the literature. METHODS Nineteen patients were phenotyped per local institutional procedures. A systematic review following PRISMA criteria identified 132 articles describing 161 patients. Main outcome analyses were performed for manifestation frequency, diagnostic delay, overall survival, symptom-free survival, and ulcer-free survival. RESULTS Our cohort presented a wide variability of severity. Autoimmune disorders were found in 6/19, including Crohn disease, systemic lupus erythematosus, and arthritis. Another immune finding was hemophagocytic lymphohistiocytosis (HLH). Half of published patients were symptomatic by age 4 and had a delayed diagnosis (mean delay 11.6 years). Ulcers were present initially in only 30% of cases, with a median age of onset at 12 years old. CONCLUSION Prolidase deficiency has a broad range of manifestations. Symptoms at onset may be nonspecific, likely contributing to the diagnostic delay. Testing for this disorder should be considered in any child with unexplained autoimmunity, lower extremity ulcers, splenomegaly, or HLH.
Barbosa M, Lopes A, Mota C, Martins E, Oliveira J, Alves S, De Bonis P, do Céu Mota M, Dias C, Ro... more Barbosa M, Lopes A, Mota C, Martins E, Oliveira J, Alves S, De Bonis P, do Céu Mota M, Dias C, Rodrigues‐Santos P, Fortuna AM, Quelhas D, Lacerda L, Bisceglia L, Cardoso ML. Clinical, biochemical and molecular characterization of Cystinuria in a cohort of 12 patients.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.
Os autores apresentam o caso de um recem-nascido do sexo masculino com hipotonia severa, succao d... more Os autores apresentam o caso de um recem-nascido do sexo masculino com hipotonia severa, succao debil, convulsoes, facies dismorfico ehepatomegalia. Esttidos subsequentes revelaram, leucodistrofia, disfuncao hepatica, aumento dos acidos gordos de cadeia muito longa (AGCML) ediminuicao da actividade enzimatica da dihidroxiacetonafosfato-aciltransferase (DHAP-AT) nos fibroblastos. Os resultados laboratoriais e a evolucaoclinica apoiam o diagnostico de Sindroma de Zellweger.
PURPOSE Prolidase deficiency is a rare inborn error of metabolism causing ulcers and other skin d... more PURPOSE Prolidase deficiency is a rare inborn error of metabolism causing ulcers and other skin disorders, splenomegaly, developmental delay, and recurrent infections. Most of the literature is constituted of isolated case reports. We aim to provide a quantitative description of the natural history of the condition by describing 19 affected individuals and reviewing the literature. METHODS Nineteen patients were phenotyped per local institutional procedures. A systematic review following PRISMA criteria identified 132 articles describing 161 patients. Main outcome analyses were performed for manifestation frequency, diagnostic delay, overall survival, symptom-free survival, and ulcer-free survival. RESULTS Our cohort presented a wide variability of severity. Autoimmune disorders were found in 6/19, including Crohn disease, systemic lupus erythematosus, and arthritis. Another immune finding was hemophagocytic lymphohistiocytosis (HLH). Half of published patients were symptomatic by age 4 and had a delayed diagnosis (mean delay 11.6 years). Ulcers were present initially in only 30% of cases, with a median age of onset at 12 years old. CONCLUSION Prolidase deficiency has a broad range of manifestations. Symptoms at onset may be nonspecific, likely contributing to the diagnostic delay. Testing for this disorder should be considered in any child with unexplained autoimmunity, lower extremity ulcers, splenomegaly, or HLH.
Barbosa M, Lopes A, Mota C, Martins E, Oliveira J, Alves S, De Bonis P, do Céu Mota M, Dias C, Ro... more Barbosa M, Lopes A, Mota C, Martins E, Oliveira J, Alves S, De Bonis P, do Céu Mota M, Dias C, Rodrigues‐Santos P, Fortuna AM, Quelhas D, Lacerda L, Bisceglia L, Cardoso ML. Clinical, biochemical and molecular characterization of Cystinuria in a cohort of 12 patients.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.
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