Haematopoietic and immune defects associated with GATA2 mutation

Heterozygous familial or sporadic GATA2 mutations cause a multifaceted disorder, encompassing susceptibility to infection, pulmonary dysfunction, autoimmunity, lymphoedema and malignancy. Although often healthy in childhood, carriers of defective GATA2 alleles develop progressive loss of mononuclear cells (dendritic cells, monocytes, B and Natural Killer lymphocytes), elevated FLT3 ligand, and a 90% risk of clinical complications, including progression to myelodysplastic syndrome (MDS) by 60 years of age. Premature death may occur from childhood due to infection, pulmonary dysfunction, solid malignancy and MDS/acute myeloid leukaemia. GATA2 mutations include frameshifts, amino acid substitutions, insertions and deletions scattered throughout the gene but concentrated in the region encoding the two zinc finger domains. Mutations appear to cause haplo‐insufficiency, which is known to impair haematopoietic stem cell survival in animal models. Management includes genetic counselling, prevention of infection, cancer surveillance, haematopoietic monitoring and, ultimately, stem cell transplantation upon the development of MDS or another life‐threatening complication.     

Celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure

BACKGROUND & AIMS: Mild liver abnormalities are common in patients with celiac disease and usually resolve with a gluten-free diet. We investigated the occurrence of celiac disease in patients with severe liver failure. METHODS: Four patients with untreated celiac disease and severe liver disease are described. Further, the occurrence of celiac disease was studied in 185 adults with previous liver transplantation using serum immunoglobulin A endomysial and tissue transglutaminase antibodies in screening. RESULTS: Of the 4 patients with severe liver disease and celiac disease, 1 had congenital liver fibrosis, 1 had massive hepatic steatosis, and 2 had progressive hepatitis without apparent origin. Three were even remitted for consideration of liver transplantation. Hepatic dysfunction reversed in all cases when a gluten-free diet was adopted. In the transplantation group, 8 patients (4.3%) had celiac disease. Six cases were detected before the operation: 3 had primary biliary cirrhosis, 1 had autoimmune hepatitis, 1 had primary sclerosing cholangitis, and 1 had congenital liver fibrosis. Only 1 patient had maintained a long-term strict gluten-free diet. Screening found 2 cases of celiac disease, 1 with autoimmune hepatitis and 1 with secondary sclerosing cholangitis. CONCLUSIONS: The possible presence of celiac disease should be investigated in patients with severe liver disease. Dietary treatment may prevent progression to hepatic failure, even in cases in which liver transplantation is considered.     

Basal insulin requirement of youth with type 1 diabetes differs according to age

We investigated the percentage of total basal insulin dose to total daily insulin dose (%TBD) among Japanese youth of different ages with type 1 diabetes. The study enrolled 69 patients with type 1 diabetes who were treated with multiple daily injections of insulin. The participants were divided into the following age groups: group A, 0 to <10 years (n = 18); group B, 10 to <20 years (n = 31) and group C, 20 to <25 years (n = 20). We found no difference in the sex ratio, body mass index, and glycated hemoglobin and 2‐h postprandial C‐peptide levels among the three groups. Participants assigned to group B had a significantly higher percentage of total daily insulin dose than those in group A and group C (49.7 ± 10.4% vs 38.5 ± 13.7% and 38.3 ± 8.2%, P = 0.0005). In conclusion, the basal insulin requirements of Japanese youth with type 1 diabetes might have an age effect that is associated with puberty.     

Topographic specializations in the retinal ganglion cell layer of Australian passerines

Thornbills, honeyeaters, and silvereyes represent an abundant group of Australian passerines, whose diversity in niche differentiation suggests a pivotal role for vision. Using stereological methods and retinal wholemounts, we studied the topographic distribution of neurons in the ganglion cell layer of insectivorous, nectarivorous, and frugivorous species occupying terrestrial and arboreal microhabitats. All species studied have a central convexiclivate fovea (peak densities from 130,000 to 160,000 cells/mm²), which is shallow in the terrestrial/insectivorous yellow‐rumped thornbill and deep in the arboreal/nectarivorous honeyeaters and frugivorous silvereye. Surrounding the fovea, neuronal densities in the ganglion cell layer form a broadly ovoid and asymmetric plateau in the yellow‐rumped thornbill and a more restricted, circular and symmetric plateau in the other species. These differences in the plateau organization may reflect specific needs to locate food on the ground or among dense vegetation. We also found a temporal area (peak densities from 43,000 to 54,000 cells/mm²) across species, which increases spatial resolution in the frontal visual field and assists with foraging. Using microtubule‐associated protein 2 (MAP2) immunohistochemistry, we detected a higher concentration of giant ganglion cells forming an area gigantocellularis in the temporal retina of all species. Giant ganglion cell densities also form a horizontal streak in all species, except in the yellow‐rumped thornbill, which has an unusual increase toward the retinal periphery. In the yellow‐rumped thornbill and silvereye, giant ganglion cells also peak in the nasal retina. We suggest that these topographic variations afford differential sampling of motion signals for the detection of predators. J. Comp. Neurol. 522:3609–3628, 2014. © 2014 Wiley Periodicals, Inc.