Screening by high-throughput sequencing for pathogenic variants in cystic fibrosis: Benefit of introducing personalized therapies.

This short report documented cystic fibrosis transmembrane conductance regulator (CFTR) variants in 37 patients with cystic fibrosis (CF) in the Rio Grande do Norte region of Northeast Brazil. The high-throughput sequencing technology (HTS) genetic testing provided a definitive molecular diagnosis in 31 patients (83.8%). Among them, 25 patients' carriers of the c.1521_1523delCTT variant, categorized as a class 2 mutation, can be currently treated with CFTR modulator drugs. Five children aged 2-5 years could benefit from double lumacaftor/ivacaftor therapy, and 20 patients aged >6 years could be treated with the triple-combination elexacaftor/tezacaftor/ivacaftor therapy. Thus, the identification of pathogenic variants associated with the development of this disease allows for the introduction of therapy with CFTR modulators that favour better patient management.

SCID and Other Inborn Errors of Immunity with Low TRECs - the Brazilian Experience.

Severe combined immunodeficiency, SCID, is a pediatric emergency that represents the most critical group of inborn errors of immunity (IEI). Affected infants present with early onset life-threatening infections due to absent or non-functional T cells. Without early diagnosis and curative treatment, most die in early infancy. As most affected infants appear healthy at birth, newborn screening (NBS) is essential to identify and treat patients before the onset of symptoms. Here, we report 47 Brazilian patients investigated between 2009 and 2020 for SCID due to either a positive family history and/or clinical impression and low TRECs. Based on clinical presentation, laboratory finding, and genetic information, 24 patients were diagnosed as typical SCID, 14 as leaky SCID, and 6 as Omenn syndrome; 2 patients had non-SCID IEI, and 1 remained undefined. Disease onset median age was 2 months, but at the time of diagnosis and treatment, median ages were 6.5 and 11.5 months, respectively, revealing considerable delay which affected negatively treatment success. While overall survival was 51.1%, only 66.7% (30/45) lived long enough to undergo hematopoietic stem-cell transplantation, which was successful in 70% of cases. Forty-three of 47 (91.5%) patients underwent genetic testing, with a 65.1% success rate. Even though our patients did not come from the NBS programs, the diagnosis of SCID improved in Brazil during the pilot programs, likely due to improved medical education. However, we estimate that at least 80% of SCID cases are still missed. NBS-SCID started to be universally implemented in the city of São Paulo in May 2021, and it is our hope that other cities will follow, leading to early diagnosis and higher survival of SCID patients in Brazil.

Germline Compound Heterozygous Variants Identified in the STXBP2 Gene Leading to a Familial Hemophagocytic Lymphohistiocytosis Type 5: A Case Report.

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, potentially fatal autosomal-recessive immunodeficiency, and STXBP2 mutations have been associated with FHL type 5 (FHL-5). Here, we report a case of a 2-year-old boy who presented with recurrent fever, hepatosplenomegaly, pancytopenia, hyperferritinemia, and hypofibrinogenemia since 4 months of age. His genetic analysis revealed a compound heterozygosity of the STXBP2 gene with a described pathogenic mutation, c.1247-1G>C (splicing acceptor site), harbored by his father and a likely pathogenic variant of uncertain significance (VUS), c.704G>A (p.Arg235Gln), harbored by his mother. He was diagnosed as compound heterozygous for FHL-5 and was treated with the HLH-2004 protocol. Since treatment, this patient has been in remission, and he is being evaluated for a hematopoietic stem cell transplantation (HSCT).

Correction to: Unusual Severe Seborrheic Dermatitis in Two Siblings with Autosomal Recessive Chronic Granulomatous Disease.

The original version of this article contained an error in Fig. 1. The incomplete heredogram mistakenly appeared in panel d.

Estudo de parâmetros salivares em crianças asmáticas usuárias de antiinflamatórios / Study of salivary parameters in asthmatic children using anti-inflammatory agents

Este estudo longitudinal compreendeu um período de 210 dias, durante os quais os parâmetros salivares pH, capacidade tampäo (CTS), velocidade do fluxo salivar (VFS) e o percentual do cálcio foram analisados mensalmente, em 14 crianças asmáticas, entre 7-13 anos de idade, usuárias de aerossol de dipropionato de beclometasona (DPB) e de cromoglicato de sódio (CGD) por igual período de 90 dias, e um grupo-controle de 35 crianças clinicamente saudáveis, näo-usuárias de medicaçäo, com a mesma faixa etária. No tratamento estatístico, utilizou-se o teste T para amostras independentes, a fim de verificar se o uso das medicaçöes por 30 dias afetaria alguns fatores de proteçäo salivar do grupo experimental em relaçäo ao grupo-controle e comparar longitudinalmente os efeitos das medicaçöes na saliva das crianças asmáticas. Concluiu-se que as alteraçöes desses fatores observadas durante o uso do DPB e CGD reforçam a necessidade de lavagem da cavidade oral após o uso dessas medicaçöes e a preconizaçäo de medidas odontológicas preventivas durante o tratamento da asma brônquica com aerossol por tempo prolongado.