Hepatitis B Virus Reactivation in a Patient With Chronic GVHD After Allogeneic Peripheral Blood Stem Cell Transplantation

We report a patient with fatal hepatitis B virus (HBV) reactivation after treatment for chronic graft-versus-host disease (GVHD) following allogeneic peripheral blood stem cell transplantation to treat chronic myelogenous leukemia. The presence of antibodies to hepatitis B surface antigen (HBsAb) prior to transplantation indicated previous HBV infection. Liver damage first developed 8 months after transplantation with the disappearance of HBsAb. Hepatitis B antigen was first noted during an examination of liver damage that occurred 22 months after transplantation. Retrospective examination of serum by real-time detection polymerase chain reaction (RTD-PCR) revealed HBV in both the first and second episodes of liver damage (89 copies/mL and 2 x 10(6) copies/mL, respectively). HBV may have been reactivated, leading to fatal liver damage in this HBsAb-positive patient. We propose that RTD-PCR-based analysis should be performed to diagnose liver dysfunction after hematopoietic stem cell transplantation.     

Clinical,biochemical and molecular analysis of 13 Japanese patients with β-ureidopropionase deficiency demonstrates high prevalence of the c.977G > A (p.R326Q) mutation

β-ureidopropionase (βUP) deficiency is an autosomal recessive disease characterized by N-carbamyl-β-amino aciduria. To date, only 16 genetically confirmed patients with βUP deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 13 Japanese βUP deficient patients. In this group of patients, three novel missense mutations (p.G31S, p.E271K, and p.I286T) and a recently described mutation (p.R326Q) were identified. The p.R326Q mutation was detected in all 13 patients with eight patients being homozygous for this mutation. Screening for the p.R326Q mutation in 110 Japanese individuals showed an allele frequency of 0.9 %. Transient expression of mutant βUP enzymes in HEK293 cells showed that the p.E271K and p.R326Q mutations cause profound decreases in activity (≤ 1.3 %). Conversely, βUP enzymes containing the p.G31S and p.I286T mutations possess residual activities of 50 and 70 %, respectively, suggesting we cannot exclude the presence of additional mutations in the non-coding region of the UPB1 gene. Analysis of a human βUP homology model revealed that the effects of the mutations (p.G31S, p.E271K, and p.R326Q) on enzyme activity are most likely linked to improper oligomer assembly. Highly variable phenotypes ranging from neurological involvement (including convulsions and autism) to asymptomatic, were observed in diagnosed patients. High prevalence of p.R326Q in the normal Japanese population indicates that βUP deficiency is not as rare as generally considered and screening for βUP deficiency should be included in diagnosis of patients with unexplained neurological abnormalities.     

Fall Risk Index predicts functional decline regardless of fall experiences among community‐dwelling elderly

Aim: The 21‐item Fall Risk Index (FRI‐21) has been used to detect elderly persons at risk for falls. The aim of this longitudinal study was to evaluate the FRI‐21 as a predictor of decline in basic activities of daily living (BADL) among Japanese community‐dwelling elderly persons independent of fall risk. Methods: The study population consisted of 518 elderly participants aged 65 years and older who were BADL independent at baseline in Tosa, Japan. We examined risk factors for BADL decline from 2008 to 2009 by multiple logistic regression analysis on the FRI‐21 and other functional status measures in all participants. We carried out the same analysis in selected participants who had no experience of falls to remove the effect of falls. Results: A total of 45 of 518 participants showed decline in BADL within 1 year. Multivariate logistic regression analysis showed that age (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.05–1.20), FRI‐21 ≥ 10 (OR 3.81, 95% CI 1.49–9.27), intellectual activity dependence (OR 3.25, 95% CI 1.42–7.44) and history of osteoarthropathy (OR 3.17, 95% CI 1.40–7.21) were significant independent risk factors for BADL decline within 1 year. FRI‐21 ≥ 10 and intellectual activity dependence (≤3) remained significant predictors, even in selected non‐fallers. Conclusion: FRI‐21 ≥ 10 and intellectual activity dependence were significant predictive factors of BADL decline, regardless of fall experience, after adjustment for confounding variables. The FRI‐21 is a brief, useful tool not only for predicting falls, but also future decline in functional ability in community‐dwelling elderly persons. Geriatr Gerontol Int 2012; ??: ??–?? .     

Association of arrhythmia and sudden death in macrocephaly–cutis marmorata telangiectatica congenita syndrome

Macrocephaly–cutis marmorata telangiectatica congenita (M‐CMTC) constitutes a distinct entity characterized by prenatal overgrowth, macrosomia, hemihypertrophy, macrocephaly, nonobstructive hydrocephaly, frontal bossing, hypotonia, developmental delay, generalized or facial capillary malformation with upper philtral nevus flammeus and cutis marmorata, joint hypermobility, loose skin, toe syndactyly, and postaxial polydactyly. All but one of the cases reported previously had benign clinical courses without showing an increased risk of early infant death. We describe three additional cases with poor clinical outcomes including severe postnatal growth failure, intractable cardiac arrhythmia in two cases, and sudden infant death in two cases. Arrhythmia has not been described previously as one of the symptoms of M‐CMCT. Patients with M‐CMTC associated with severe postnatal growth failure and arrhythmia may constitute a distinct clinical subtype of M‐CMTC with an increased risk of life‐threatening episodes or sudden death. Recognizing this clinical subtype of M‐CMTC is important to prevent these serious potential complications. © 2001 Wiley‐Liss, Inc.