Exploring the potential association among sleep disturbances,cognitive impairments,and immune activation in 22q11.2 deletion syndrome

22q11.2 deletion syndrome (22q11.DS) is a neurogenetic disorder caused by a microdeletion in chromosome 22. Its phenotype includes high rates of psychiatric disorders, immune system abnormalities, and cognitive impairments. We assessed the quality of sleep in 22q11.2DS and its potential link to inflammatory markers and cognitive deficits. Thirty‐three 22q11.2DS individuals and 24 healthy controls were studied. Sleep parameters were assessed by the Pittsburgh sleep quality index (PSQI) questionnaire and correlated with serum cytokine levels and cognitive functioning, measured using the Penn computerized neurocognitive battery (CNB). The 22q11.2DS individuals had significantly worse sleep quality scores than the controls, unrelated to the psychiatric or physical comorbidities common to 22q11.2DS. Interleukin 6 levels were correlated with the overall score of the PSQI questionnaire for nonpsychotic 22q11.2DS participants only. Several domains of the CNB were associated with poorer sleep quality, suggesting that cognitive impairments in 22q11.2DS may be at least partially explained by poor sleep quality. Our findings confirm sleep impairments in individuals with 22q11.2DS, which might negatively affect their cognitive functioning, and corroborate a potential role of immunological pathways in the 22q11.2DS neuro‐phenotype.     

Pepsinogens and other serum markers in pernicious anemia

Pepsinogen (PG) I and PG II levels were determined in sera from 147 patients with pernicious anemia. Race, sex, age, gastrin level, and antibody status did not influence pepsinogen levels. PG I values less than 30 micrograms/L were found in 92% of cases and PG I to PG II ratios less than 3.0 in 82% of cases. At least one of these two results was abnormal in 97% of all patients with pernicious anemia. In comparison, results of other blood tests used in the investigation of pernicious anemia were less often abnormal. Serum gastrin level exceeded 200 ng/L in 90% of patients with pernicious anemia and was second to pepsinogen abnormality in diagnostic sensitivity. Results for anti-intrinsic factor antibody were positive in 73% of cases and anti-parietal cell antibody in only 52%. Although its specificity is limited, the presence of low PG I level and/or low PG I-PG II ratio is currently the most sensitive serum indicator for pernicious anemia, and absence of both can be taken as a strong argument against the diagnosis. This highly sensitive test can be combined further with the highly specific serum anti-intrinsic factor antibody test for the presumptive diagnosis of pernicious anemia when definitive tests (the Schilling test or gastric analysis for intrinsic factor) cannot be done or results are inconclusive.     

Racial differences in vitamin B12 levels in the United States

Studies from Africa have demonstrated that black people have higher vitamin B12 (cobalamin) levels than do white people. The authors compared healthy white people, black people, and Latin-Americans in the United States. Their study is also the largest in which the effect of race and sex on the cobalamin levels has been examined. Analysis of 233 healthy subjects showed that black people had significantly higher (P less than 0.0001) vitamin B12 levels than did white people. Latin-Americans had levels intermediate between those of white and black people, although their levels were significantly different only in comparison with white people (P = 0.0029). Based on the study of 305 healthy subjects, no sex difference in vitamin B12 levels was noted. Conflicting claims have been made on sex difference in the past. The authors conclude that there is a racial but not a sex difference in vitamin B12 levels in the United States. Like African black people, black people and Latin-Americans in this country have significantly higher vitamin B12 levels than do white people. This finding supports the thesis that genetic factors contribute to the racial differences in vitamin B12 levels.     

Blood transfusion in medically treatable chronic anemia. Pernicious anemia as a model for transfusion overuse

Transfusion practice in patients with treatable, readily recognizable, chronic anemia was reviewed because such patients only infrequently need to be transfused. Pernicious anemia with hemoglobin concentration below 100 g/L was chosen as the model for this assessment. Sixty-two (51%) of 122 patients received blood transfusion, although most patients had chronic, low-grade symptoms despite their low hemoglobin levels and could have been satisfactorily managed without transfusion. Only 34 of the 122 had findings suggesting an urgent need to raise the blood cell count, but their transfusion rate (44%) was no different from that in patients without such findings. These observations in pernicious anemia indicate that transfusion of patients with medically reversible anemia is a common problem. They further suggest that current transfusion usage overemphasizes laboratory results (ie, hemoglobin levels) at the expense of clinical assessment of severity of symptoms. Improvement of current practice is needed, particularly in view of valid concerns about the serious side effects of transfusion, shortages of available blood resources, and health care costs.     

Epidemiology of achondroplasia: A population‐based study in Europe

Achondroplasia is a rare genetic disorder resulting in short‐limb skeletal dysplasia. We present the largest European population‐based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. All cases of achondroplasia notified to 28 EUROCAT registries (1991–2015) were included in the study. Prevalence, birth outcomes, prenatal diagnosis, associated anomalies, and the impact of paternal and maternal age on de novo achondroplasia were presented. The study population consisted of 434 achondroplasia cases with a prevalence of 3.72 per 100,000 births (95%CIs: 3.14–4.39). There were 350 live births, 82 terminations of pregnancy after prenatal diagnosis, and two fetal deaths. The prenatal detection rate was significantly higher in recent years (71% in 2011–2015 vs. 36% in 1991–1995). Major associated congenital anomalies were present in 10% of cases. About 20% of cases were familial. After adjusting for maternal age, fathers >34 years had a significantly higher risk of having infants with de novo achondroplasia than younger fathers. Prevalence was stable over time, but regional differences were observed. All pregnancy outcomes were included in the prevalence estimate with 80.6% being live born. The study confirmed the increased risk for older fathers of having infants with de novo achondroplasia.