A novel nonsense mutation of the KAL1 gene (p.Trp204*) in Kallmann syndrome.

OBJECTIVE: To describe a novel KAL1 mutation in patients affected by Kallmann syndrome. SETTING: Endocrinology Clinic of the João de Barros Barreto University Hospital - Federal University of Pará, Brazil. METHODS: Clinical examination, hormone assays and sequencing of exons 5, 6 and 9 of the KAL1 gene in four Brazilian brothers with Kallmann syndrome. RESULTS: Detected a novel KAL1 mutation, c.612G.A/p.Trp204*, in four hemizygous brothers with Kallmann syndrome, and five heterozygous female family members. CONCLUSION: The novel p.Trp204* mutation of the KAL1 gene results in the production of a truncated anosmin-1 enzyme in patients with Kallmann syndrome. This finding broadens the spectrum of pathogenic mutations for this disease.

Mutations, clinical findings and survival estimates in South American patients with X-linked adrenoleukodystrophy.

UNLABELLED: In this study, we analyzed the ABCD1 gene in X-linked adrenoleukodystrophy (X-ALD) patients and relatives from 38 unrelated families from South America, as well as phenotypic proportions, survival estimates, and the potential effect of geographical origin in clinical characteristics. METHODS: X- ALD patients from Brazil, Argentina and Uruguay were invited to participate in molecular studies to determine their genetic status, characterize the mutations and improve the genetic counseling of their families. All samples were screened by SSCP analysis of PCR fragments, followed by automated DNA sequencing to establish the specific mutation in each family. Age at onset and at death, male phenotypes, genetic status of women, and the effect of family and of latitude of origin were also studied. RESULTS: We identified thirty-six different mutations (twelve novel). This population had an important allelic heterogeneity, as only p.Arg518Gln was repeatedly found (three families). Four cases carried de novo mutations. Intra-familiar phenotype variability was observed in all families. Out of 87 affected males identified, 65% had the cerebral phenotype (CALD). The mean (95% CI) ages at onset and at death of the CALD were 10.9 (9.1-12.7) and 24.7 (19.8-29.6) years. No association was found between phenotypic manifestations and latitude of origin. One index-case was a girl with CALD who carried an ABCD1 mutation, and had completely skewed X inactivation. CONCLUSIONS: This study extends the spectrum of mutations in X-ALD, confirms the high rates of de novo mutations and the absence of common mutations, and suggests a possible high frequency of cerebral forms in our population.

Erros inatos do metabolismo: revisão de literatura / Inborn errors of metabolism: literature review

Objetivo: estudo de revisão sobre Erros Inatos do Metabolismo (EIM). Método: realizado por levantamento de dados nas bases MEDLINE e LILACS. Conclusões: compreendem alterações enzimáticas de origem genética responsáveis pr manifestações metabólicas em que há falha de síntese, degradação, armazenamento ou transporte de moléculas no organismo. Os Erros Inatos do Metabolismo são clássicos distúrbios genéticos, tornando-se importante conhecê-los´para um bom aconselhamento familiar que inclua, principalmente, o prognóstico do paciente e o risco de recorrência da doença

Perfil epidemiológico de portadores de hipotireoidismo congênito / Epidemiologic profile of congenital hypothyroidism patients

Objetivo: determinar o perfil epidemiológico de crianças portadoras de hipotireoidismo congênito (HC). Método: analisados os prontuários de 131 pacientes com diagnóstico de HC acompanhados na Unidade de Referência Especializada Materno Infantil e Adolescente (URE-MIA) do Estado do Pará, segundo variáveis como idade, sexo, procedência, realização do teste do pezinho e tempo do diagnóstico. Resultados: observou-se que 55% dos casos estudados eram provenientes da Grande Belém; a prevalência segundo o sexo demonstrou predomínio do feminino com 58%; aproximadamente 48% das crianças realizaram o teste do pezinho antes dos 30 dias de vida e o tratamento foi instituído até os 90 dias em 57,3% dos pacientes; os principais sinais observados, no momento da admissão, foram: hérnia umbilical (59,5%), macroglossia (42,7%), atraso no desenvolvimento neuropsicomotor (39,7%), obstipação intestinal (36,6%) e hipoatividade (34,4%). Conclusão: predomínio de crianças do sexo feminino e provenientes da Grande Belém. A procedência das crianças foi fator determinante no tempo de intervenção diagnóstica e terapêutica, apontando lacunas no Programa de Triagem Neonatal do Estado do Pará.

Objective: to determine the epidemiologic profile of congenital hypothyroidism (CH). Method: information about age, sex, hometown, neonatal screening test and age of diagnosis was collected from 131 CH patients assisted inl the reference service of the State of Pará. Results: it was shown that 55% of the cases were from Belém region. Thel prevalence according to sex showed a female predominance (58%). Roughly 48% of the children have been tested before 30 days of age and the treatment have begun until 90 days in 57,3% of patients. The main signs observed at the admission act were: umbilical hernia (59,5%), macroglossia (42,7%), neurological development delay, (39,7%), intestinal obstruction (36,6%) and lack of activity (34,4%). Conclusion: predominance of female children. Most of them were from the capital region. The origin of the children was a relevant factor about the diagnosis and treatment time, pointing out to faults in the Neonatal Screening Program of the state of Pará.