GATA2 deficiency detected by newborn screening for SCID: A case report

The early diagnosis and treatment of inborn errors of immunity (IEI) is crucial in reducing the morbidity and mortality due to these disorders. The institution of newborn screening (NBS) for the diagnosis of Severe Combined Immune Deficiency (SCID) has decreased the mortality of this disorder and led to the discovery of novel genetic defects that cause this disease. GATA2 deficiency is an autosomal dominant, pleiotropic disease with clinical manifestations that include bone marrow failure, monocyte and B cell deficiency, leukemia, pulmonary alveolar proteinosis and lymphedema. We present the case of an infant identified by newborn screening for SCID due to GATA2 deficiency

Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is caused by defects in any 1 of the 6 subunits forming the nicotinamide adenine dinucleotide phosphate oxidase complex 2 (NOX2), leading to severely reduced or absent phagocyte-derived reactive oxygen species production. Almost 50% of patients with CGD have inflammatory bowel disease (CGD-IBD). While conventional IBD therapies can treat CGD-IBD, their benefits must be weighed against the risk of infection. Understanding the impact of NOX2 defects on the intestinal microbiota may lead to the identification of novel CGD-IBD treatments. OBJECTIVE: We sought to identify microbiome and metabolome signatures that can distinguish individuals with CGD and CGD-IBD. METHODS: We conducted a cross-sectional observational study of 79 patients with CGD, 8 pathogenic variant carriers, and 19 healthy controls followed at the National Institutes of Health Clinical Center. We profiled the intestinal microbiome (amplicon sequencing) and stool metabolome, and validated our findings in a second cohort of 36 patients with CGD recruited through the Primary Immune Deficiency Treatment Consortium. RESULTS: We identified distinct intestinal microbiome and metabolome profiles in patients with CGD compared to healthy individuals. We observed enrichment for Erysipelatoclostridium spp, Sellimonas spp, and Lachnoclostridium spp in CGD stool samples. Despite differences in bacterial alpha and beta diversity between the 2 cohorts, several taxa correlated significantly between both cohorts. We further demonstrated that patients with CGD-IBD have a distinct microbiome and metabolome profile compared to patients without CGD-IBD. CONCLUSION: Intestinal microbiome and metabolome signatures distinguished patients with CGD and CGD-IBD, and identified potential biomarkers and therapeutic targets

Infection prophylaxis patterns following pediatric autologous hematopoietic stem cell transplantation: A survey of Pediatric Transplant and Cell Therapy Consortium centers

No standardized guidelines exist for infectious prophylaxis following pediatric auto‐HSCT. We hypothesized significant variation in clinical practice. Thirty‐three Pediatric Transplant and Cell Therapy Consortium centers completed a survey to assess institutional management. The majority utilize viral (91%) and fungal prophylaxis (94%), but duration varies. Bacterial prophylaxis during neutropenia is instituted by 42%. Our study demonstrates marked practice variability in infectious prophylaxis across centers. Additional research is needed to address patterns of infectious complications and to develop meaningful clinical practice guidelines for pediatric auto‐HSCT.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163606/3/petr13821.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163606/2/petr13821_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163606/1/petr13821-sup-0001-FigS1.pd

Infection prophylaxis patterns following pediatric autologous hematopoietic stem cell transplantation: A survey of Pediatric Transplant and Cell Therapy Consortium centers

No standardized guidelines exist for infectious prophylaxis following pediatric auto‐HSCT. We hypothesized significant variation in clinical practice. Thirty‐three Pediatric Transplant and Cell Therapy Consortium centers completed a survey to assess institutional management. The majority utilize viral (91%) and fungal prophylaxis (94%), but duration varies. Bacterial prophylaxis during neutropenia is instituted by 42%. Our study demonstrates marked practice variability in infectious prophylaxis across centers. Additional research is needed to address patterns of infectious complications and to develop meaningful clinical practice guidelines for pediatric auto‐HSCT.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163606/3/petr13821.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163606/2/petr13821_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163606/1/petr13821-sup-0001-FigS1.pd