Hemoglobin variant in disguise.

BACKGROUND: Hemoglobinopathies include thalassemia syndromes, where production of one or more globin subunits of hemoglobin (Hb) is reduced, and structural Hb variants. Over 1000 disorders of Hb synthesis and/or structure have been identified and characterized, with phenotypes ranging from having severe clinical manifestations to clinically silent. Various analytical methods are used to phenotypically detect Hb variants. However, molecular genetic analysis is a more definitive method for Hb variant identification. CASE REPORT: Here, we report a case of a 23-month-old male with results from capillary electrophoresis, gel electrophoresis (acid and alkaline), and high-performance liquid chromatography most consistent with HbS trait. Specifically, capillary electrophoresis showed slightly elevated HbF and HbA2, HbA of 39.4% and HbS of 48.5%. The HbS percentage was consistently higher than expected (typically 30-40%) for HbS trait with no concurrent thalassemic indices. The patient has not experienced any clinical complications due to the hemoglobinopathy and he is thriving. CONCLUSION: Molecular genetic analysis revealed the presence of compound heterozygosity for HbS and Hb Olupona. Hb Olupona is an extremely rare beta-chain variant that appears as HbA on all three common methods used for phenotypic Hb analysis. When the fractional concentration of Hb variants is unusual, more definitive methods should be used, such as mass spectrometry or molecular genetic testing. In this case, incorrectly reporting this result as HbS trait is unlikely to have a significant clinical impact, as current evidence suggests Hb Olupona is not a clinically significant variant.

Influence of fasting and sample collection time on 38 biochemical markers in healthy children: a CALIPER substudy.

OBJECTIVES: Fasting samples can be difficult to obtain in the pediatric setting, particularly in neonates. As part of the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER), we aimed to determine if there are differences in serum concentrations of pediatric biochemical markers measured at fasting, postprandial, and random time points throughout the day. DESIGN AND METHODS: Blood was drawn from 27 healthy children and adolescents (aged 4-18) with informed consent at 4 time points: after overnight fast, mid-morning after breakfast, within 2h after lunch, and late afternoon. The effect of fasting on 38 chemistries was evaluated by paired, two-tailed student'st-tests. Analysis of the effect of time of day was done using paired, repeated-measures ANOVA. RESULTS: Fasting significantly affected 22 analytes, with HDL cholesterol being the most highly affected. Values tended to decrease postprandially, except for five analytes, including triglycerides, which increased. By ANOVA, 28 chemistries significantly differed across times of day tested. CONCLUSIONS: Fasting is necessary for analysis of certain chemistries in pediatric subjects. Pediatricians should consider diurnal factors when ordering non-fasting tests and interpreting test results.

New insight into the mechanism of action of IVIg: the role of dendritic cells.

Intravenous immunoglobulin (IVIg) is used to treat an ever-increasing number of autoimmune diseases. While the exact mechanism of action of IVIg has remained elusive, many theories have been suggested, including mononuclear phagocytic system blockade, autoantibody neutralization by anti-idiotype antibodies, accelerated pathogenic autoantibody clearance by saturation of the neonatal Fc receptor, cytokine modulation and complement neutralization. More recently, a key role for dendritic cells (DC) in the amelioration of autoimmunity by IVIg has been suggested. Here we will focus on the role that DC may play in IVIg function using data from both mouse and human studies.