RESUMO
Gaucher disease is a lysosomal storage disorder caused by a deficiency of the enzyme acid ß-glucosidase. In order to determine the mutation spectrum in Tunisia, we performed recurrent mutation screening in 30 Tunisian patients with Gaucher disease. Screening of recurrent mutation by PCR/RFLP and direct sequencing had shown that N370S was the most frequent mutation (22/50 mutant alleles, 44%), followed by L444P mutation, which is found in 16% (8/50 mutant alleles). The recombinant allele (RecNciI) represented 14%. Our findings revealed that the genotype N370S/RecNciI was mosst frequent in patients with childhood onset and it was associated with severe visceral involvement. The screening of these three mutations provided a simple tool for molecular diagnosis of Gaucher disease in Tunisian patients and allowed also genetic counselling for their family members.
Assuntos
Doença de Gaucher/diagnóstico , Doença de Gaucher/genética , Técnicas de Diagnóstico Molecular , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Análise Mutacional de DNA/métodos , Feminino , Doença de Gaucher/complicações , Doença de Gaucher/epidemiologia , Predisposição Genética para Doença , Genótipo , Glucosilceramidase/genética , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição/fisiologia , Tunísia/epidemiologia , Adulto JovemRESUMO
The glycogen storage disease type Ia (GSD Ia) is a rare inherited disorder, with autosomal recessive determinism. It is characterized by hepatomegaly, short stature and hypoglycemia with lactic acidemia. The confirmation of diagnosis is based on the enzymatic assay performed on liver biopsy. For Tunisians patients, this biochemical test is performed abroad. The aim of our study is the molecular characterization of GSD Ia in Tunisian patients and the development of a molecular diagnosis tool. Our study included 27 patients from 23 unrelated families, mutation analysis revealed that the R83C mutation is the most frequent (65%, 30/46 mutant alleles), followed by the R170Q mutation (30%, 14/46 mutant alleles). The homogeneity of mutation spectrum of GSD Ia in Tunisia allows the development of a cost effective and reliable tool for the confirmation of clinical diagnosis among suspected GSD Ia patients.
Assuntos
Doença de Depósito de Glicogênio Tipo I/genética , Mutação/genética , Sequência de Bases , DNA/análise , Análise Mutacional de DNA , Glucose-6-Fosfatase/análise , Glucose-6-Fosfatase/genética , Doença de Depósito de Glicogênio Tipo I/diagnóstico , Heterozigoto , Homozigoto , Humanos , Fígado/enzimologia , Fígado/patologia , TunísiaRESUMO
Idiopathic nephrotic syndrome (INS) is the most frequent glomerular nephropathy in children. The response to corticoids distinguishes steroid-sensitive nephrotic syndrome (SSINS), by far the most frequent (90% of cases), from steroid-resistant nephrotic syndrome (SRINS). The steroid resistance of nephrotic syndrome is defined by the absence of remission after a full dose of oral corticosteroid therapy for 1 month followed by 3 pulses of intravenous methylprednisolone. Actually, INS constitutes a heterogeneous nosologic entity. Currently, within the SRINS, there are 2 forms that vary greatly in their physiopathology and prognostics: immunologic or sporadic forms, which can be improved by immunosuppressive agents and the genetic or familial forms, which do not respond to any immunosuppressive therapy and usually evolve to end-stage renal insufficiency. In these genetic forms, renal transplantation is the only therapeutic alternative. The aim of this article is to review treatment of SRINS and to propose a management strategy.
Assuntos
Corticosteroides/efeitos adversos , Síndrome Nefrótica/terapia , Corticosteroides/administração & dosagem , Resistência a Medicamentos , Inibidores Enzimáticos/uso terapêutico , Humanos , Técnicas de Imunoadsorção , Imunossupressores/uso terapêutico , Transplante de Rim , PlasmafereseRESUMO
Glycogen storage disease type Ia (GSD Ia; OMIM 232200) is an autosomal recessive disorder of glycogen metabolism caused by a deficiency of the microsomal glucose-6-phosphatase (G6Pase). It is characterized by short stature, hepatomegaly, hypoglycaemia, hyperuricaemia, and lactic acidaemia. Various mutations have been reported in the G6Pase gene (G6PC). In order to determine the mutation spectrum in Tunisia, we performed mutation analysis in 22 Tunisian type I glycogen storage disease (GSD I) patients belonging to 18 unrelated families. All patients were clinically classified as GSD Ia. The R83C mutation was found to be the major cause of GSD Ia, accounting for 24 of 36 mutant alleles (66.6%), The R170Q mutation was the second most frequent mutation; it accounts for 10 of 36 mutant alleles (27.7%). The R83C and R170Q mutations could be rapidly detected by PCR/RFLP. Since the majority of Tunisian patients carried R83C and/or R170Q mutations, we propose direct screening of these mutations as a rapid, valuable and noninvasive tool for diagnosis of GSD Ia in Tunisian as well as in Northern African populations.
Assuntos
Análise Mutacional de DNA/métodos , Glucose-6-Fosfatase/genética , Doença de Depósito de Glicogênio Tipo I/diagnóstico , Doença de Depósito de Glicogênio Tipo I/genética , Alelos , Humanos , Mutação , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , TunísiaRESUMO
UNLABELLED: Mycoplasma pneumoniae infection is associated with various manifestations involving the central nervous system but it has never been reported as a potential aetiology of opsoclonus-myoclonus syndrome (OMS) in children. OBSERVATION: We report on a case in a 4-year-old girl who presented neurological manifestations compatible with an OMS, after a respiratory tract disease. Aetiological investigations revealed M. pneumoniae infection as specific IgM were present in the serum (Elisa). Evolution after corticosteroid, intravenous immunoglobulins and macrolide therapy was favourable as clinical symptoms disappeared. After a 12-month follow-up, the patient has no neurological sequela. CONCLUSION: M. pneumoniae infection should be added to the list of causes to be screened in OMS. Its pathophysiology remains unknown but may involve a dysimmune postinfectious mechanism.
Assuntos
Mycoplasma pneumoniae/isolamento & purificação , Síndrome de Opsoclonia-Mioclonia/microbiologia , Pneumonia por Mycoplasma/complicações , Corticosteroides/uso terapêutico , Pré-Escolar , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Macrolídeos/uso terapêutico , Metilprednisolona/uso terapêutico , Síndrome de Opsoclonia-Mioclonia/tratamento farmacológico , Pneumonia por Mycoplasma/tratamento farmacológicoRESUMO
INTRODUCTION: Down syndrome is a favourable land to the emergence of auto-immune disease. CASE RECORD: Graves' disease and celiac disease were diagnosed in a 16 years old adolescent with Down syndrome presenting chronic diarrhoea, important delayed development and signs of hyperthyroidism. DISCUSSION: Celiac disease and thyroid dysfunction would be screening in patient with Down syndrome.
Assuntos
Doença Celíaca/complicações , Síndrome de Down/complicações , Doença de Graves/complicações , Adolescente , Doença Celíaca/diagnóstico , Síndrome de Down/diagnóstico , Feminino , Doença de Graves/diagnóstico , HumanosRESUMO
OBJECTIVE: The authors had for aim to determine the role of leukoconcentration in the diagnosis of visceral leishmaniosis in immunocompetent children. MATERIALS AND METHODS: A study was made on leukoconcentration in blood samples of 84 immunocompetent children presenting with visceral leishmaniosis, hospitalised in the paediatric units of Sousse and Kairouan (Tunisian center) between April 1996 and March 2005. RESULTS: The study group included 34 girls and 50 boys (sex-ratio = 1.47) aged six months to ten years. In this group, 47 patients (56%) presented with positive leukoconcentration. The number of leishmania detected ranged from 1 to 64 per slide; parasitism of PMN leucocytes was noted in nearly half of the cases. CONCLUSION: Parasitemia is frequent in the Mediterranean Kala-azar; therefore leukoconcentration on peripheral blood can be proposed as a first intention examination for the diagnosis of visceral leishmaniosis in immunocompetent children.
Assuntos
Leishmaniose Visceral/sangue , Leishmaniose Visceral/diagnóstico , Contagem de Leucócitos , Criança , Humanos , Pacientes Internados , TunísiaRESUMO
Recurrent bacterial meningitis is an uncommon disease of childhood. It occurs most often in children who have an underlying predisposing disorder that can result from anatomic fistula or immunodeficiency. Cochleovestibular dysplasia is a rare malformation of the inner ear that is often associated with translabyrinthine cerebrospinal fistula and then can cause recurrent bacterial meningitis. We report an unusual case of recurrent meningitis revealing cochleovestibular dysplasia in a 9-year-old child. The malformation was confirmed by imaging and the child had surgery. The outcome was favourable with no recurrence of meningitis during the 3 years after the operation.
Assuntos
Cóclea/patologia , Meningites Bacterianas/etiologia , Vestíbulo do Labirinto/patologia , Criança , Cóclea/anormalidades , Feminino , Humanos , Imageamento por Ressonância Magnética , Recidiva , Tomografia Computadorizada por Raios X , Vestíbulo do Labirinto/anormalidadesRESUMO
UNLABELLED: Systemic mastocytosis is rare in children and is characterized by an abnormal proliferation and infiltration of mast cells in different tissues. CASE REPORT: We report a case of systemic mastocytosis presenting cutaneous symptoms during the neonatal period. Later evolution was characterized by systemic manifestations consisting of recurrent respiratory infections with wheezing and a digestive involvement that included abdominal pain, hepatosplenomegaly and a nodular, hemorrhagic infiltrate in a low esophagus. The diagnosis was confirmed by histology and biology, notably increased histamine concentrations in blood and urines. Improvement of the respiratory and digestive symptoms was obtained with treatment by histamine H1 and H2 receptors antagonists. CONCLUSION: Respiratory manifestations and nodular infiltration of the digestive tract are rare in systemic mastocytosis. The prognosis is conditioned by complications such as malignancy and the persistence of the disease till the adult age.
Assuntos
Doenças do Esôfago/etiologia , Mastocitose/complicações , Infecções Respiratórias/etiologia , Dor Abdominal/etiologia , Feminino , Hemorragia Gastrointestinal/etiologia , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Recém-Nascido , Mastocitose/diagnóstico , Mastocitose/tratamento farmacológico , Sons Respiratórios , Esplenomegalia/etiologiaRESUMO
OBSERVATION: A 10-year-old boy presented cholestatic hepatitis A virus infection confirmed by IGM anti-HAV antibody. Three days after admission, he presented a palpable purpuric rash on the declivous regions, arthralgia and abdominal pain. He met all criteria set by the American College of Rheumatology (ACR) for Henoch Schonlein purpura. The evolution was gradually favorable with no renal involvement (recoil of 3 years and half). CONCLUSION: Henoch Schonlein purpura is an exceptional extra-hepatic manifestation of hepatitis A infection.
Assuntos
Hepatite A/complicações , Vasculite por IgA/diagnóstico , Criança , Humanos , Vasculite por IgA/complicações , Vasculite por IgA/virologia , MasculinoRESUMO
UNLABELLED: Mixed connective tissue disease (MTCD) is a systemic inflammatory disorder individualised by Sharp et al. in 1972. This entity is rare in children. CASE REPORT: We report an exceptional case of MTCD revealed by lymphocytic meningitis in a two-month-and-a-half-old infant. The disease was diagnosed at the age of nine months when clinical symptomatology was completed by common signs of the illness (Raynaud's phenomenon, swollen hands), systemic lupus erythematosus-like symptoms (lymphadenopathy, squamous erythema of the limbs, hepato-splenomegaly, pleuritis and ascites) and polymyositis-like findings (muscle weakness with increased serum levels of myogenic enzymes). Laboratory investigations showed an important inflammatory syndrome and the presence of speckled anti-nuclear and anti-U(1)RNP antibodies. Specific antibodies of the other connective tissue diseases were also positive (anti-DNA, anti-Sm, anti-SSA and SSB, anti-Scl 70 and JO1) pleading for the mixed feature of the illness. The follow-up after corticosteroid treatment was marked by clinical and biological improvement. But after five months, the patient died following a severe infectious complication. CONCLUSION: Chronic lymphocytic meningitis can be part of Sharp's syndrome even in infants. However, the diagnosis relies on the evidence of characteristic clinical and biological abnormalities of MTCD.
Assuntos
Meningite/complicações , Doença Mista do Tecido Conjuntivo/diagnóstico , Doença Crônica , Feminino , Humanos , Lactente , Linfócitos , Meningite/imunologia , Doença Mista do Tecido Conjuntivo/complicaçõesAssuntos
Reação Leucemoide/complicações , Febre Tifoide/complicações , Feminino , Humanos , LactenteRESUMO
NADPH oxidase, a multi-subunit protein consisting of cytosolic components and the membrane-bound heterodimer, plays an instrumental role in host defence mechanisms of phagocytes. Genetic deficiency of the enzymatic complex results in an inherited disorder, chronic granulomatous disease (CGD), which is characterized by an impaired phagocyte microbicidal activity. X-Linked (XL) CGD results from a mutation in the CYBB gene encoding the gp91phox subunit, while autosomal recessive (AR) CGD is associated with mutations in one of the NCF1, NCF2 and CYBA genes that encode the p47phox, p67phox and p22phox subunits, respectively. In the study reported here, we investigated genetic defects underlying CGD in 15 Tunisian patients from 14 unrelated families. Haplotype analyses and homozygosity mapping with microsatellite markers around known CGD genes assigned the genetic defect to NCF1 in four patients, to NCF2 in four patients and to CYBA in two patients. However, one family with two CGD patients seemed not to link the genetic defect to any known AR-CGD genes. Mutation screening identified two novel mutations in NCF2 and CYBA in addition to the recurrent mutation, DeltaGT, in NCF1 and a splice site mutation previously reported in a North African patient. Our results revealed the genetic and mutational heterogeneity of the AR recessive form of CGD in Tunisia.