RESUMO
AIM: The aim of the present study was to characterize the molecular basis of complement factor I deficiency in Tunisian atypical haemolytic and uremic syndrome patients with low factor I levels. METHODS: Six adults and seven children were enrolled in this study. Complement factor I levels were assessed by a homemade sandwich ELISA and ranged between 12.5% and 60%. Genomic DNA was amplified by way of a polymerase chain reaction using intronic primers flanking the 13 coding exons. Sequencing of amplified products was carried out by the dye terminator sequencing method. Molecular study was performed on parental samples for three dead paediatric patients. The control group consisted of 100 healthy Tunisian donors. RESULTS: We identified a total of 13 substitutions and one insertion: seven in introns, four in exons and three in UTR. The new mutations were c.-132G > C, c.71 + 181 T > A in 5'UTR and intron 1, respectively. Three intronic polymorphisms were predicted to have impact on splicing events: c.482 + 6C > T, c.884-42_884-41insTTAAA (rs34422850) and c.1429 + 33 A > G (rs9998151). They were three missense mutations leading to a p.Ile 357Met, p.Ile416Leu and p.GLu548Gln. p.Ile 357Met was found in two patients and one relative. Half of the patients had associated mutation and/or polymorphisms. CONCLUSION: This is the first genetic study in Tunisian and Maghrebin atypical haemolytic and uraemic syndrome patients. The high occurrence of Ile357Met mutation may reflect a founding effect. Functional impact of the two new mutations c.-132G > C and c.71 + 181A > T have to be studied. Association of simultaneous genetic abnormalities may explain the variability of atypical haemolytic and uraemic syndrome, penetrance and disease phenotype.
Assuntos
Síndrome Hemolítico-Urêmica Atípica , Complemento C3/deficiência , Fator I do Complemento , Doenças Genéticas Inatas , Adulto , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/epidemiologia , Síndrome Hemolítico-Urêmica Atípica/genética , Criança , Pré-Escolar , Estudos de Coortes , Complemento C3/genética , Fator I do Complemento/análise , Fator I do Complemento/genética , Feminino , Doenças Genéticas Inatas/sangue , Doenças Genéticas Inatas/epidemiologia , Doenças Genéticas Inatas/genética , Doenças da Deficiência Hereditária de Complemento , Humanos , Lactente , Masculino , Mutação , Polimorfismo Genético , Tunísia/epidemiologiaRESUMO
BACKGROUND: Zinc (Zn) deficiency is a common condition and could contribute to poor outcomes in hemodialysis (HD) patients. The aim of this study was to evaluate the effects of Zn supplementation on serum copper (Cu) to Zn and C-reactive protein (CRP) to albumin ratios (CAR) in HD patients. METHODS: Seventy-seven HD patients were enrolled in a multicentre simple-blind randomized clinical trial. Only 37 HD patients completed the study; they were randomly divided into two groups and supplemented with zinc sulphate (n=17) or placebo (n=20) for two months. Serum Zn and Cu were measured by atomic absorption spectrophotometry. Serum albumin and hypersensitive-CRP were assessed by colorimetric and immunoturbidimetric method, respectively. Determinations were performed before and after supplementation. RESULTS: After two months of supplementation, serum Zn significantly increased, and Cu to Zn ratio decreased in Zn supplemented group, but remained unchanged in the placebo group. In parallel, serum albumin concentrations significantly increased, and CAR decreased in Zn supplemented group only. CONCLUSIONS: Zn supplementation reduces Cu to Zn and CRP to albumin ratios in HD patients. These changes point towards an improvement in nutritional, oxidative and inflammatory status. The study findings suggest that correcting Zn deficiency reduces poor outcomes in HD patients.
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Thalidomide, which is an angiogenesis inhibitor and immunomodulator that reduces tumor necrosis factor-alpha, has regained value in the treatment of multiple myeloma. Serious pulmonary complications due to thalidomide use remain relatively uncommon. We describe a case of bronchiolitis obliterans organizing pneumonia (BOOP) due to thalidomide. A 51-year-old man with IgG lambda myeloma was treated with thalidomide and dexamethasone. Seven days after the beginning of chemotherapy, the patient presented a fever and a persistent cough. Auscultation revealed crackles in both pulmonary bases. The chest X-ray showed a diffuse bilateral alveolar-interstitial syndrome. Computed tomography scan revealed bilateral pulmonary involvement, with bilateral interstitial alveolar infiltration and ground-glass pattern consolidations. Pulmonary infection, malignant tumor, and lung involvement of multiple myeloma were excluded through various tests. Thalidomide-induced BOOP was suspected, and the drug was withdrawn and replaced by Melphalan. The patient had complete resolution of his symptoms and radiologic pulmonary involvement on discontinuation of the drug. In the absence of other etiologies, physicians should be cognizant of this potential complication in patients receiving thalidomide who present with respiratory symptoms.
Assuntos
Antineoplásicos/efeitos adversos , Pneumonia em Organização Criptogênica/induzido quimicamente , Mieloma Múltiplo/tratamento farmacológico , Talidomida/efeitos adversos , Antineoplásicos/administração & dosagem , Pneumonia em Organização Criptogênica/diagnóstico por imagem , Substituição de Medicamentos , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Talidomida/administração & dosagem , Resultado do TratamentoRESUMO
Crow-Fukase syndrome, also known as POEMS syndrome, is a rare plasma dyscrasia characterized by monoclonal gammopathy and various combinations of polyneuropathy, organomegaly, endocrinopathy and dermatological changes, and their initials stand for the acronym POEMS. Substantial kidney involvement is rarely related to this disease. Our report is about five patients suffering from the POEMS syndrome with kidney involvement that rapidly progressed to end-stage renal disease. Our report is about three females and two males with a mean age of 60.6 years. Neuropathy was noted in all the cases. Endocrinopathy included hypothyroidism and/or diabetes. Skin changes were noted in one case, and included peri-orbital hyperpigmentation. Monoclonal gammopathy was present in all the cases and was related to multiple myeloma in three cases. Kidney involvement presented in all the five cases. Treatment included Melphalan, Thalidomid, steroids and hemodialysis. Survival was short for three patients, from five to 34 months.