Clinical and genetic analysis of a child with neonatal severe parathyroidism / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with neonatal severe hyperparathyroidism.@*METHODS@#Genomic DNA was extracted from peripheral blood samples from the patient and her parents. Whole exome sequencing was carried out to screen potential mutations. Suspected mutation was verified by Sanger sequencing.@*RESULTS@#The proband was found to carry compound heterozygous variants c.179G>A (p.Cys60Tyr) and c.1525G>A (p.Gly509Arg) of the CaSR gene. The c.179G>A variant was derived from her mother and was unreported previously. The c.1525G>A variant was derived from her father and known to be pathogenic.@*CONCLUSION@#The compound heterozygous variants of c.179G>A and c.1525G>A of the CaSR gene probably underlie the disease in the patient. The results of genetic testing has enabled diagnosis and genetic counseling for her family.

Hallermann-streiff syndrome a case report from Egypt

Hallermann-Streiff syndrome [HSS] is a rare genetic disorder that is primarily characterized by distinctive malformations of the skull and facial [craniofacial] region; sparse hair [hypotrichosis]; eye abnormalities; dental defects; degenerative skin changes [atrophy], particularly in the scalp and nasal regions; and proportionate short stature. Here we describe a case with HSS

Prediction of sepsis-related outcomes in neonates through systematic genotyping of polymorphisms in genes for innate immunity and inflammation: a narrative review and critical perspective / Previsao de desfechos relacionados a sepse em neonatos atraves da genotipagem sistematica de polimorfismos de genes da imunidade inata e inflamacao: uma revisao narrativa e perspectiva critica

CONTEXT AND OBJECTIVE: Neonatal sepsis is associated with premature birth and maternal infection. Large-scale studies seek to define markers that identify neonates at risk of developing sepsis. Here, we examine whether the scientific evidence supports systematic use of polymorphism genotyping in cytokine and innate immunity genes, to identify neonates at increased risk of sepsis. DESIGN AND SETTING: Narrative literature review conducted at Fernandes Figueira Institute, Brazil. METHODS: The literature was searched in PubMed, Embase (Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde), SciELO (Scientific Electronic Library Online) and Cochrane Library. From > 400,000 references, 548 were retrieved based on inclusion/exclusion criteria; 22 were selected for detailed analysis after quality assessment. RESULTS: The studies retrieved addressed the impact of gene polymorphisms relating to immune mechanisms (most often TNF-a, LT-a, IL-6, IL-1β, IL-1ra, L-selectin, CD14 and MBL) or inflammatory mechanisms (ACE and angiotensin II receptors; secretory PLA2; and hemostatic factors). Despite initial reports suggesting positive associations between specific polymorphisms and increased risk of sepsis, the accumulated evidence has not confirmed that any of them have predictive power to justify systematic genotyping. CONCLUSIONS: Sepsis prediction through systematic genotyping needs to be reevaluated, based on studies that demonstrate the functional impact of gene polymorphisms and epidemiological differences among ethnically distinct populations. .

CONTEXTO E OBJETIVO: A sepse neonatal está associada ao parto prematuro e à infecção materna. Estudos em grande escala buscam marcadores que identifiquem neonatos em risco de desenvolver sepse. Examinamos aqui se a evidência científica apoia o uso sistemático de genotipagem dos polimorfismos em genes de citocinas e imunidade inata, para identificar neonatos com risco elevado de sepse. TIPO DE ESTUDO E LOCAL: Revis ão narrativa da literatura, Instituto Fernandes Figueira, Brasil. M ÉTODOS: Busca online da literatura foi feita no PubMed, Embase (Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde), SciELO (Scientific Electronic Library Online) e Cochrane Library. De mais de 400.000 referências, 548 foram recuperadas com base nos critérios de inclusão/exclusão, e 22, selecionadas para análise detalhada após verificação da qualidade. RESULTADOS: Recuperamos estudos de impacto dos polimorfismos em genes relacionados com mecanismos imunes (mais frequentemente, TNF-a, LT-a, IL-6, IL-1 β, IL-1ra, L-selectin, CD14, e MBL) ou inflamatórios (ACE e receptores de angiotensina II; PLA2 secretória; fatores hemostáticos). Contrariando estudos que inicialmente sugeriram associação positiva entre polimorfismos específicos e risco aumentado de sepse, a evidência acumulada não confirmou, para qualquer deles, valor preditivo que justifique genotipagem sistemática para orientar antibioticoterapia. CONCLUSÕES: A previsão da sepse por meio de genotipagem sistemática precisa ser reavaliada, com base em estudos que demonstram o impacto funcional de polimorfismos gênicos e as diferenças epidemiológicas entre populações etnicamente distintas. .

Triagem neonatal para imunodeficiência combinada grave / Newborn screening for severe combined immunodeficiency

As imunodeficiências primárias (IDP) são uma área recente e aindapouco conhecida da medicina. Pacientes com IDP apresentam, na maior parte dos casos, infecções graves e recorrentes de início precoce, elevada morbidade e mortalidade, resultando frequentemente em sequelas,elevado custo social e sofrimento dos familiares. Embora na Américado Norte e Europa se estime que sua incidência seja semelhante à dafenilcetonúria e do hipotireoidismo congênito (afecções congênitas quecontam com triagem neonatal), ainda faltam dados quanto à sua real incidência na população brasileira.O projeto em desenvolvimento no Instituto de Ciências Biomédicasda USP e Escola Paulista de Medicina da UNIFESP, visa contribuir para o avanço na implementação de testes de triagem neonatal para asimunodeficiências primárias, mais especificamente, ImunodeficiênciasCombinadas Graves, que constituem um grupo de doenças com diferentesdefeitos genéticos, que evoluem para o óbito precoce se não foremdiagnosticadas e tratadas a tempo e a Síndrome de DiGeorge, que seestima ser a síndrome genética de deleção mais prevalente (1:3.000nascidos vivos).Seguindo esta linha de pensamento, nossa hipótese é que no Brasilexiste um número desconhecido de pacientes com IDP não diagnosticadosou subdiagnosticados que após a implementação de técnicas de detecção molecular por triagem neonatal para a SCID e síndrome de DiGeorge, passarão a ser contabilizados e tratados corretamente, diminuindo portanto,a morbidade e mortalidade.

Primary immunodeficiency disorders (PIDD) are a recently-recognizedand relatively unstudied area of medicine. Patients with PIDD frequentlypresent with the early onset of severe recurrent infections, high morbidityand mortality, frequently resulting in sequelae, high social cost, andfamily burden. While in North America and Europe it is estimated thatits incidence is similar to phenylketonuria and congenital hypothyroidism(congenital disorders that rely on neonatal screening), there is a lack ofdata on its actual incidence in Brazil.The project being developed at Institute of Biomedical Sciences,University of São Paulo and Federal University of São Paulo MedicalSchool, aims to contribute to the implementation of neonatal screeningtests for primary immunodeficiencies. More specifically, severe combinedimmunodeficiencies, a group of diseases with several genetic defects,may progress to early death if not diagnosed and treated early in life;and DiGeorge Syndrome, which is estimated to be the most prevalentgenetic deletion syndrome (1:3,000).Our hypothesis is that, in Brazil there is an unknown number ofpatients with undiagnosed or underdiagnosed disease, which, after theimplementation of detection techniques through newborn screening forSCID and DiGeorge Syndrome, will be accounted for and treated properly,reducing therefore, the morbidity and mortality.

Long-term response to sulfonylurea in a patient with diabetes due to mutation in the KCNJ11 gene / Resposta a longo prazo com sulfonilureia em um paciente com diabetes associado à mutação no gene KCNJ11

OBJECTIVE: To report the long-term (30-month) effect of the switch from insulin to sulfonylurea in a patient carrying the p.G53D (c.158G>A) mutation in KCNJ11 gene. SUBJECT AND METHOD: A 29-year-old male patient was diagnosed with diabetes in the third month of life and after identification of a heterozygous p.G53D mutation in the KCNJ11 gene, the therapy was switched from insulin to sulfonylurea. RESULTS: Long-term follow-up (30 months) showed that good metabolic control was maintained (HbA1c: 6.6 percent) and the glibenclamide dose could be reduced. CONCLUSION: Long-term therapy with sulfonylureas in patients with neonatal diabetes due to mutation in the KCNJ11 gene is safe and promotes sustained improvement of glycemic control.

OBJETIVO: Reportar o efeito a longo prazo (30 meses) da substituição de insulina por sulfonilureia em um paciente com a mutação p.G53D (c.158G>A) no gene KCNJ11. SUJEITO E MÉTODO: Paciente do sexo masculino, atualmente com 29 anos de idade, foi diagnosticado com diabetes melito no terceiro mês de vida e, após identificação da mutação p.G53D (c.158G>A) em heterozigose no gene KCNJ11, a terapia foi substituída de insulina para sulfonilureia. RESULTADOS: Seguimento a longo prazo (30 meses) mostrou que o bom controle metabólico foi mantido (HbA1c: 6,6 por cento) e a dose de glibenclamida pode ser reduzida. CONCLUSÃO: A terapia com sulfonilureia a longo prazo em pacientes com diabetes neonatal decorrente de mutações no gene KCNJ11 é segura e promove uma melhora persistente no controle metabólico.

Atresia congénita del colon: reporte de un caso y revisión de la literatura / Congenital colon atresia: case repòrt review

Se informa el primer caso de atresia congénita de colon diagnosticado y operado en el Hospital de Especialidades del Instituto Hondureño de Seguridad Social en Tegucigalpa. Se trata de una paciente de sexo femenino que se presentó al tercer día de vida en la Sala de Emergencia con cuadro de obstrucción intestinal. Fue intervenido quirúrgicamente encontrando una atresia de colon a nivel de ángulo esplénico realizándole una coloplastía reductiva mas anastomósis colocólica en un plano. Evolucionó satisfactoriamente dándosele el alta al octavo día postoperatorio. La paciente se controla periódicamente en la Consulta Externa de Cirugía. su control regular demuestra una evolución asintomática con peso y talla adecuado a los 10 meses de edad...

Endogamy, consanguinity and community genetics.

The population of India is composed of many thousands of subpopulations, divided by geography, language, religion and caste or biraderi (patrilineage) boundaries, with endogamous marriage the norm. The net effect has been the creation of multiple genetic isolates with individual mutation profiles, but to date the clinical consequences of this highly complex differentiation have been largely ignored. In contrast, the topic of consanguinity continues to attract attention among medical and population geneticists, clinicians and social scientists. The significant progress made in India in improving childhood nutritional status and combating infectious disease means that genetic disorders have assumed ever-increasing importance. In populations where consanguineous marriage is widely practised, recessive genetic disorders will continue to gain greater prominence in the overall spectrum of ill health. At the same time this increase will in part be negated by urbanization and the move to smaller family sizes, which predictably will result in a decline in the prevalence of consanguineous unions. Developing an understanding of these changes will require a wide-ranging and multidisciplinary investigative approach for which community genetics is ideally suited.

Hipertiroidismo neonatal: presentación de 2 pacientes / Neonatal hyperthyroidism. Report of 2 cases

Se presentaron 2 pacientes con diagnóstico de hipertiroidismo neonatal: uno del sexo masculino y otro del femenino; con antecedentes de ser hijos de madres con enfermedad de Graves; una de ellas se encontraba sin tratamiento, y con síntomas de hipertiroidismo y la otra con tratamiento y tenía controlada esa afección. Se realizó el diagnóstico por los antecedentes de ser hijos de madres con enfermedad de Graves Basedow; así como por las manifestaciones clínicas: bocio, exoftalmos, pérdida de peso, irritabilidad, taquicardia e insuficiencia cardíaca en uno de los pacientes. Según los exámenes de laboratorio realizados, se obtuvieron los resultados siguientes: T4 ³ 180 nmol/L y TSH < 1 mU/L, en ambos pacientes. Se les indicó tratamiento con propiltiuracilo, propranolol y fenobarbital, así como medidas generales y digitálicos en el paciente que lo requirió. Se logró una evolución favorable en ambos pacientes(AU)

2 patients with diagnosis of neonatal hyperthyroidism, a male and a female, are presented. Their mothers suffer from Graves' disease, one of them has no treatment and presents symptoms of hyperthyroidism, and the other is under treatment and her disease is under control. The diagnosis was made taking into account that they are children from mothers with Graves Basedow' disease and the following clinical manifestations: goiter, exophthalmos, weight loss, irritability, tachycardia and cardiac insufficiency in one of the patients. The results of the laboratory tests for both patients were: T4 ³ l80 nmol/L and TSH < 1 U/L. Treatment with propylthiouracilo, propanolol and phenobarbital as well as general measures and digitalis therapy in the patient requiring it were indicated. A favorable evolution was observed in these 2 patients(AU)