Recurrent episodes of life-threatening myoglobinuria in childhood are caused by inborn errors of glycogenolysis, mitochondrial fatty acid beta-oxidation, and oxidative phosphorylation. Nonetheless, approximately half of the patients do not suffer from a defect in any of these pathways. Using homozygosity mapping, we identified six deleterious mutations in the LPIN1 gene in patients who presented at 2-7 years of age with recurrent, massive rhabdomyolysis. The LPIN1 gene encodes the muscle-specific phosphatidic acid phosphatase, a key enzyme in triglyceride and membrane phospholipid biosynthesis. Of six individuals who developed statin-induced myopathy, one was a carrier for Glu769Gly, a pathogenic mutation in the LPIN1 gene. Analysis of phospholipid content disclosed accumulation of phosphatidic acid and lysophospholipids in muscle tissue of the more severe genotype. Mutations in the LPIN1 gene cause recurrent rhabdomyolysis in childhood, and a carrier state may predispose for statin-induced myopathy.

Aims: Over 75% of obese subjects fail to maintain their weight following weight loss interventions. We aimed to identify phenotypic and genetic markers associated with weight maintenance/regain following a dietary intervention. Subjects and methods: In the 2-year Dietary Intervention Randomized Controlled Trial, we assessed potential predictors for weight changes during the 'weight loss phase' (0-6 months) and the 'weight maintenance/regain phase' (7-24 months). Genetic variation between study participants was studied using single-nucleotide polymorphisms in the leptin gene (LEP). Results: Mean weight reduction was À5.5% after 6 months, with a mean weight regain of 1.2% of baseline weight during the subsequent 7-24 months. In a multivariate regression model, higher baseline high-molecular-weight adiponectin was the only biomarker predictor of greater success in 0-to 6-month weight loss (b ¼ À0.222, P-value ¼ 0.044). In a multivariate regression model adjusted for 6-month changes in weight and various biomarkers, 6-month plasma leptin reduction exhibited the strongest positive association with 6-month weight loss (b ¼ 0.505, P-valueo0.001). Conversely, 6-month plasma leptin reduction independently predicted weight regain during the following 18 months (b ¼ À0.131, P-valueo0.013). Weight regain was higher among participants who had a greater (top tertiles) 6-month decrease in both weight and leptin ( þ 3.4% (95% confidence interval 2.1-4.8)) as compared with those in the lowest combined tertiles ( þ 0.2% (95% confidence interval À1.1 to 1.4)); P-valueo0.001. Weight regain was further significantly and independently associated with genetic variations in LEP (P ¼ 0.006 for both rs4731426 and rs2071045). Adding genetic data to the phenotypic multivariate model increased its predictive value for weight regain by 34%. Conclusion: Although greater reduction in leptin concentrations during the initial phase of a dietary intervention is associated with greater weight loss in the short term, plasma leptin reduction, combined with the degree of initial weight loss and with genetic variations in the LEP gene, constitutes a significant predictor of subsequent long-term weight regain.

Table 1 contains errors in the ''Genotype'' column. The mutation of patient L.R. should be described as c.2401C/T, R801X. The mutation of patient D.A. should be described as c.192þ2T/C leading to the deletion of the last 106 nt of exon 2, and the mutation of patient P.N. should be described as c.1441þ2T/C leading to the skipping of exon 9 (exon and nucleotide numbering according to NM_145693). A corrected version of the table is included below. The authors regret these errors.

Purpose Chronic kidney disease (CKD) negatively affects health-related quality of life (HRQoL), which is often measured using the Medical Outcomes Study Short Form 36 (SF-36) questionnaire. However, the adequacy of SF-36 in this population has not been reported. We aimed to determine floor and ceiling effects and responsiveness to change of SF-36 in patients with conservatively managed stage 5 CKD.MethodsSF-36 data were collected prospectively. Floor and ceiling effects were estimated for each SF-36 scale and summary measure based on raw scores. The minimal clinically important difference (MCID) was estimated using a combination of anchor-based and distribution-based methods. Responsiveness to change was assessed by comparing MCID for each scale and summary measure to its smallest detectable change.ResultsSF-36 data were available for 73 of the 74 study participants. Using baseline data, floor and/or ceiling effects were detected for 3 of the 8 SF-36 scales. The anchor-based estimation of MCID based on differences in baseline functional status yielded the most reliable results. For the physical component summary, MCID was estimated at 5.7 points. Whilst the two SF-36 summary measures were responsive to change and free of floor and/or ceiling effects, six of the eight scales were not.ConclusionsThis small study of patients with conservatively managed stage 5 CKD found that only the summary measures of SF-36 and 2 of its 8 scales can be used to assess changes in HRQoL over time. These findings suggest that in this population, alternative HRQoL assessment tools should be considered for future studies.