Levels of Lyso GL-1 in Gaucher and Lyso GL-3 in Fabry patients from India: Diagnostic aids for these lysosomal storage disorders.

BACKGROUND & AIMS: Lysosomal storage disorders (LSDs) remain a significant cause of morbidity in the Indian population and treatment is largely out of reach for most patients. Although data on enzymatic and molecular diagnosis of Gaucher disease (GD) and Fabry disease (FD) in Indian patients are available, the present study intended to establish the pathogenic levels of Lyso GL-1 and Lyso GL-3 in patients of GD and FD respectively as diagnostic aids. MATERIALS AND METHODS: From 2017 to 2019, ninety confirmed Gaucher cases (by enzymatic and molecular analysis) were tested for chitotriosidase (fluorometrically) and Lyso GL-1 (LC-MS/MS) and ten confirmed Fabry cases were analyzed for Lyso GL-3 (LC-MS/MS). RESULTS: Lyso GL-1 (median: 685.5 ng/mL, cut-off: 14) and Lyso GL-3 (median: 75.6 ng/mL, cut-off: 3.5) were found to be elevated in all enzymatically deficient patients of GD and FD respectively, however, no specific trend was observed between the levels of these biomarkers and the pathogenic variant(s) present in the patients of these disorders. CONCLUSIONS: This is the first report on Lyso GL-1 and Lyso GL-3 levels in Indian patients of GD and FD respectively. These results will be useful for early diagnosis to improve management of these LSDs.

A competing risk analysis of death patterns in male genitourinary cancer.

BACKGROUND: Early diagnosis and improved therapeutic options have contributed to prolonged survival in male genitourinary cancer. However, these cancer survivors may die due to other causes. AIMS: This work is aimed to explore the death patterns among male genitourinary cancer patients due to other causes. The occurrence of death not related to cancer is defined as competing risk (CR). METHODS AND RESULTS: Data extracted between 1973 and 2014 for male patients (n = 638 393) diagnosed with genitourinary cancer and registered in the Surveillance, Epidemiology, and End Results (SEER) Program were included for analysis. A CR analysis was performed to explore the death patterns due to cancer or otherwise. Our study evidenced a huge proportion of patients' death due to associated factors including but not limited to cancer. Interestingly, the computed hazard ratios obtained in cancers of male organ sites such as prepuce, glans penis, penis, and spermatic cord were 1.28 (0.98-1.67), 1.53 (1.33-1.77), 1.35 (0.19-1.53), and 1.57 (1.24-2.0), respectively. However, the hazard ratios evaluated on factors other than cancer in the same organ sites were 0.95 (0.76-1.18), 1.14 (0.99-1.3), 1.09 (0.97-1.22), and 1.12 (0.86-1.46), respectively. CONCLUSION: This study shows that among the male genitourinary cancer patients, the significant proportion of deaths occurs due to reasons unrelated to cancer. It can be concluded that the magnitude of death due to only genitourinary cancer is minimal and is not as high as documented in the earlier literature.

Newborn Screening for Congenital Hypothyroidism, Congenital Adrenal Hyperplasia, and Glucose-6-Phosphate Dehydrogenase Deficiency for Improving Health Care in India.

Newborn screening (NBS) aims toward early detection of treatable congenital disorders. From January 2008 through December 2017, 13,376 newborns were screened for congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), and glucose-6-phosphate dehydrogenase (G6PD) deficiency at Sir Ganga Ram Hospital, India, by measuring G6PD activity, thyroid-stimulating hormone, and 17-hydroxyprogesterone on dried blood specimens. The birth prevalence of 1:2,000 for CH, 1:2,500 for CAH, and 1:125 for G6PD deficiency indicates the latter as the most prevalent. Performance evaluation of testing reveals a robust screening program with 100% sensitivity and >99% specificity. Hence, we recommend NBS for early diagnosis and treatment to prevent adverse outcomes.

WITHDRAWN: Commentary on: A systematic review and meta-analysis of risk factors for unruptured intracranial aneurysm growth.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.ijsu.2019.08.018. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Expression signature of lysosomal-associated transmembrane protein 4B in hepatitis C virus-induced hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma is a lethal disease worldwide and therefore the establishment of novel diagnostic biomarkers is imperative. In this study, it was hypothesized that an abnormal expression of the lysosomal-associated protein transmembrane 4 beta ( LAPTM4B) gene is crucial in the pathogenesis of hepatitis C virus-mediated hepatocellular carcinoma; hence we investigated the expression profile of LAPTM4B in hepatitis C virus-induced hepatocellular carcinoma. METHODS: A group of 189 consecutive patients (hepatitis C virus-related hepatocellular carcinoma as tumor cases; n=93, hepatitis C virus-related cirrhotics as disease controls; n=96) opting for living donor liver transplantation as a therapeutic surgical regimen were recruited with informed consent. Additionally, paired adjacent non-tumorous tissues (n=93) obtained from cases were also included. Serum LAPTM4B protein concentrations were assessed by third-generation enzyme-linked immunosorbent assay and LAPTM4B mRNA, and protein expressions at tissue level were determined by quantitative real time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry techniques, respectively. RESULTS: LAPTM4B protein concentrations in sera of patients were higher ( p<0.001) in tumor cases (1.25±0.25 ng/ml) compared to disease controls (0.53±0.28 ng/ml). Our study also depicts positive clinicopathological correlations between alpha-fetoprotein titers (b=0.65; p<0.001), quantitative hepatitis C virus RNA copies (b=0.33; p<0.001), and LAPTM4B protein concentrations, all in sera of patients. In addition, qRT-PCR and immunohistochemistry analyses revealed a significantly higher ( p<0.05) tissue LAPTM4B mRNA and protein expression, respectively, in tumor cases rather than in non-tumorous tissues and disease controls. CONCLUSIONS: Together, our results illustrate the LAPTM4B gene as a diagnostic biomarker in patients with hepatocellular carcinoma having documented evidence of chronic hepatitis C virus infection.

Influence of BCL11A, HBS1L-MYB, HBBP1 single nucleotide polymorphisms and the HBG2 XmnI polymorphism On Hb F levels.

In search of genetic alterations responsible for high fetal hemoglobin (Hb F) phenotypes in the population of eastern India, 91 probands were screened for four polymorphisms by sequencing and/or restriction fragment length polymorphism (RFLP) analysis. These are the A>G allele on the rs4895441 locus in the intergenic region between HBS1L and MYB on chromosome 6, the G>A allele on the rs4671393 locus on chromosome 2 (BCL11A gene), the A>C allele on the rs2071348 (HBBP1 gene) and the XmnI polymorphism (rs7482144, -158 position of HBG2) on chromosome 11. We found a significant association (p = 0.002 and 0.0013) of Hb F levels with rs2071348 and rs4895441, respectively. However, the polymorphism rs4671393 gene did not show significant association with Hb F levels (p = 0.0655). As is well known, the XmnI polymorphism (p <0.0001) showed the strongest association.

Hb Sallanches [alpha104(G11)Cys-->Tyr, TGC>TAC] occurs frequently on the Indian subcontinent.

Point mutations of alpha-globin genes in homozygous or in compound heterozygous states cause severe alpha-thalassemia (alpha-thal). Here we describe a polymerase chain reaction-restriction fragment length polymorphism-based method for easy detection of the point mutation Hb Sallanches [alpha104(G11)Cys-->Tyr, TGC>TAC], earlier detected by a sequencing technique. In a cohort of 104 unrelated putative alpha-thal patients, nine carried the mutation and two were homozygotes. The mutation occurred on both the alpha2- or alpha1-globin genes. The phenotypes, in conjunction with other point mutations or deletions, are presented. Earlier detected in Pakistan and Punjab of India, it is probably present all over the Indian subcontinent.