RESUMEN
Background Primary immunodeficiencies (PID) are a group of heterogeneous and relatively rare diseases. Aim to determine the clinical characteristics, outcome and genetic data of primary immunodeficiencies in pediatrics patients. Methods A retrospective, descriptive and multicentered study, enrolling 33 children presenting a PID in Tunis, during a period of 22 years (1991-2012). Resultats a masculine predominance has been noticed with a sex ratio at 2,3. Consanguinity was found in 71% of family cases. History of early infant deaths was found in 42% of cases. The media age of diagnosis was of 1 year 2 months. The median diagnosis delay was of 11 months and 1/2. Most frenquently observed PID were combined immunodeficiency (36%), mostly severe combined immunodeficiency (SCID) (21%), followed by congenial defects of phagocyte function (33%), mostly chronic granulomatosis disease (21%). Antibody defects were found in 21% of cases. Most frequently observed out comes were lung infections (66%) recurrent oral thrush (57%) and diarrhea (42%). Most important complications were severe infections and bronchiectasis. 30% of patients were dead by the end of the study. A molecular characterization was performed in 33% of patients, and an antenatal diagnosis was performed in 10% of cases. Conclusion The PID are a group of disease with variable expressions and etiologies. Their frequency remains understimated in Tunisia, and their management, difficult and insufficient. We suggest the establishment of systematic genetic consulting visit, the creation of a national registry and developing bone marrow transplantation in children in Tunisia.
Asunto(s)
Bronquiectasia/epidemiología , Síndromes de Inmunodeficiencia/epidemiología , Infecciones/epidemiología , Bronquiectasia/etiología , Consanguinidad , Diagnóstico Tardío , Femenino , Humanos , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/genética , Lactante , Infecciones/etiología , Masculino , Estudios Retrospectivos , Distribución por Sexo , Túnez/epidemiologíaRESUMEN
Methionyl-tRNA synthetase (MARS) catalyzes the ligation of methionine to tRNA and is critical for protein biosynthesis. We identified biallelic missense mutations in MARS in a specific form of pediatric pulmonary alveolar proteinosis (PAP), a severe lung disorder that is prevalent on the island of Réunion and the molecular basis of which is unresolved. Mutations were found in 26 individuals from Réunion and nearby islands and in two families from other countries. Functional consequences of the mutated alleles were assessed by growth of wild-type and mutant strains and methionine-incorporation assays in yeast. Enzyme activity was attenuated in a liquid medium without methionine but could be restored by methionine supplementation. In summary, identification of a founder mutation in MARS led to the molecular definition of a specific type of PAP and will enable carrier screening in the affected community and possibly open new treatment opportunities.
Asunto(s)
Metionina-ARNt Ligasa/genética , Proteinosis Alveolar Pulmonar/genética , Adolescente , Alelos , Niño , Preescolar , Retículo Endoplásmico/genética , Retículo Endoplásmico/patología , Femenino , Aparato de Golgi/genética , Aparato de Golgi/patología , Humanos , Masculino , Mutación Missense , Biosíntesis de Proteínas , Proteinosis Alveolar Pulmonar/patología , Adulto JovenRESUMEN
BACKGROUND: The frequency of cystic fibrosis is unknown in Tunisia, regarding the limited number of reported surveys and patients. AIM: to determine the clinical characteristics, outcome and genetic data of cystic fibrosis in Tunisian pediatric patients. METHODS: Cases of cystic fibrosis managed at pediatric departments of Tunis, during 15 years (1997-2012), were reviewed. RESULTS: 33 children (23 males and 10 females) were enrolled. The Onset was within the first year of life in 26 patients. Revealing symptoms were the following: recurrent bronchopneumonia (28 cases), chronic diarrhea (17 cases), hepatomegaly (6 cases), malnutrition (15 cases), pseudo Bartter syndrome (3 cases), edemaanemia- hypoprotidemia (4 cases) and meconium ileus (4 cases). The diagnosis was confirmed by sweat test and genotypic data, the F508 del was the most frequent mutation (17 cases). Several complications had occurred during follow-up: chronic pseudomonas aeruginosa infection (15 cases), chronic respiratory failure (14 cases), recurrent hemoptysis (2 cases), pleural effusion (3 cases) and cirrhosis (2 cases). Ten patients died at a mean age of 7 years. One patient had pulmonary transplantation. Prenatal diagnosis was performed in 9 families. CONCLUSION: In Tunisia, cystic fibrosis is not exceptional, but its diagnosis is delayed. Our survey is characterized by more severe earliest forms, difficult and insufficient therapeutic management. A Better medical awareness and a national action plan are needed.
Asunto(s)
Fibrosis Quística/diagnóstico , Fibrosis Quística/complicaciones , Fibrosis Quística/epidemiología , Diagnóstico Tardío , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Túnez/epidemiologíaRESUMEN
BACKGROUND: Hypophosphatasia is a rare inherited disorder characterized by defective bone and teeth mineralization and deficiency of serum and bone alkaline phosphatase activity. Several mutations in the TNSALP gene are identified. AIM: The authors describe a Tunisian case having a mutation that has not been described up to now. CASE: It is about an infant, in the antecedents of recurring disease of the lungs in child since the age of seven months, which presents clinical and radiological signs of rickets. The diagnosis of hypophosphatasia is strongly suspected in front of Reduced serum alkaline phosphatase activity and confirmed by the genetic study. The child is homozygous for a new mutation L282P in the ninth exon of the gene. The parents and two brother and sister are heterozygous for the same mutation.
Asunto(s)
Hipofosfatasia/genética , Mutación/genética , Fosfatasa Alcalina/genética , Exones/genética , Estudios de Seguimiento , Homocigoto , Humanos , Lactante , Leucina/genética , Masculino , Prolina/genéticaRESUMEN
Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency inherited as an autosomal recessive genetic disorder. LAD was suspected in a four days old girl. She was born from healthy first cousins. A family history of a boy who died from omphalitis and sepsis was reported. Our patient had the severe form, she had delayed umbilical cord separation and suffered recurrent infections. She had a deletion of the G at position 1497. The patient received bone marrow transplantation from her HLA-identical mother at age of 14 months. She is now 9 years old and in good health.
Asunto(s)
Síndrome de Deficiencia de Adhesión del Leucocito , Trasplante de Médula Ósea , Niño , Consanguinidad , Femenino , Humanos , Síndrome de Deficiencia de Adhesión del Leucocito/diagnóstico , Síndrome de Deficiencia de Adhesión del Leucocito/genética , Síndrome de Deficiencia de Adhesión del Leucocito/cirugía , Resultado del Tratamiento , TúnezRESUMEN
Pulmonary alveolar proteinosis (PAP) is a rare disorder in children. This report describes two siblings in whom PAP developed during infancy (three years for the boy and four years two months for the girl). The girl was admitted for chronic respiratory distress. Chest x-ray showed a reticulonodular pattern. Her brother was asymptomatic. The diagnosis of PAP was confirmed by open lung biopsy for the boy and broncho-alveolar lavage for the girl. Therapeutic broncho-alveolar lavages were performed (six for the girl and two for the boy), the girl lost dependence on oxygen therapy. 6 years later, the brother is still asymptomatic. The sister had two episodes of respiratory distress, after two and four years, that required therapeutic lavages. The last therapeutic bronch-oalveolar lavage was performed for the first time by a Tunisian team.
Asunto(s)
Proteinosis Alveolar Pulmonar/genética , Biopsia , Lavado Broncoalveolar , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Pulmón/patología , Masculino , Proteinosis Alveolar Pulmonar/diagnóstico , Proteinosis Alveolar Pulmonar/diagnóstico por imagen , Proteinosis Alveolar Pulmonar/patología , Proteinosis Alveolar Pulmonar/terapia , Radiografía Torácica , Factores de TiempoRESUMEN
The authors report a case of acute post infectious leukoencephalitis observed in a tow-years and a half children admitted to our hospital for fiver with suddent condition deterioration, obnibulation, coma and paralysis of the 6th and 7th cranial nerve. Cerebrospinal fluid study showed lymphocytosis with negative culture. Head magnetic resonance imaging demonstrated diffuse high signals over the white matter on T2 weighted images so the diagnosis was confirmed. High dose corticosteroid therapy was effective.