Rare mutations in ATL3, SPTLC2 and SCN9A explaining hereditary sensory neuropathy and congenital insensitivity to pain in a Brazilian cohort.

Hereditary sensory neuropathies (HSN) are a group of rare neurological disorders with heterogeneous clinical and genetic characteristics. Although at least 17 different genes have already been associated with HSN, the epidemiology of the disorder in Brazil is still unknown. Performing whole genome sequencing (WGS) in 23 unrelated Brazilian families diagnosed with HSN, we detected pathogenic variants in ATL3, SPTLC2, and SCN9A in 12 patients belonging to five unrelated families. Clinical features associated with heterozygous mutations in ATL3 (c.575A > G; p.(Tyr192Cys)) and SPTLC2 (c.529A > G; p.(Asn177Asp)) were sensory deficits, neuropathic pain, and recurrent ulcerations. Presenting as congenital insensitivity to pain, three unrelated probands carried biallelic loss-of-function mutations in SCN9A. The so far undescribed stop mutation c.2106G > A (p.(Trp702Ter)) and the likewise novel splicing variant c.3319-1G > A were found in compound-heterozygosity with, respectively, the known pathogenic variants c.2908G > T (p.Trp970Ter) and c.2690G > A (p.Glu897Ter). In total, we identified pathogenic mutations in 21.7% of our families, which suggests that most of the cases could be explained by yet to be discovered genes or unusual alleles. Our study represents the first mutational screen in a Brazilian HSN cohort, enabling additional insights for genotype-phenotype correlations, reducing misdiagnoses, and providing early treatment considerations.

Associação de Diabetes Mellitus com transtornos alimentares / Association of Diabetes Mellitus with eating disorders

O objetivo deste estudo foi revisar na literatura a associa��o do Diabetes Mellitus com os transtornos alimentares, bem como a influ�ncia desses transtornos sobre o controle metab�lico de pacientes com Diabetes Mellitus. Realizaram-se consultas aos bancos de dados Biblioteca Regional de Medicina ? Centro Latino-Americano e do Caribe de Informa��o em Ci�ncias da Sa�de; National Library of Medicine, Estados Unidos, e Scientific Electronic Library Online, publicados on-line entre 1992 e 2013, bem como trabalhos acad�micos e livros-texto. A maioria dos estudos revelou que a omiss�o/redu��o de insulina e o transtorno alimentar no Diabetes Mellitus Tipo 1 estiveram relacionados ao deficiente controle metab�lico, enquanto que a compuls�o alimentar no Diabetes Mellitus tipo 2 (com sobrepeso ou obesidade) parece ter rela��o com preju�zo na sa�de f�sica. H� v�rios relatos de que o Diabetes Mellitus tipo 2 associado ao transtorno da compuls�o alimentar peri�dica n�o influencia os resultados da Hemoglobina A Glicosilada. Al�m disso, h� evid�ncias de maior incid�ncia de depress�o entre os pacientes diab�ticos, fato que parece estar vinculado a altera��es no curso cl�nico da doen�a. Deve-se investigar a presen�a de comorbidades, como o transtorno alimentar no paciente com Diabetes Mellitus, visto que, juntos, os dist�rbios representam um problema no tratamento deste grupo de pacientes, tornando necess�rio um olhar atento na preserva��o do controle metab�lico adequado e na manuten��o da qualidade de vida dos pacientes.

The aim of this study was to review in the literature the association between diabetes and eating disorders, as well as the influence of this disorders on the metabolic control of patients with diabetes mellitus. There were queries to Regional Library of Medicine - The Latin American and Caribbean Center of information on Health Sciences, National Library of Medicine, United States and Scientific Electronic Library Online databases published on-line between 1992 and 2013 as well as theses and textbooks. Most studies have showed that the omission / reduction of insulin and eating disorders in type 1 diabetes were related to poor metabolic control, while binge eating in type 2 diabetes (with overweight or obesity) appears to be related to impaired physical health. There are several reports in which the type 2 diabetes associated with binge eating disorder have no influence on the results of Hemoglobin A, Glycosylated. Moreover, there is evidence of higher incidence of depression among diabetic patients, a fact that seems to be linked to changes in the clinical course of disease. The presence of comorbidities should be investigated such as eating disorders in Diabetes Mellitus patient, because together, disorders represent a problem in treating this group of patients, requiring a close eye on the preservation of adequate metabolic control and maintenance of quality of life of patients.