Glucose Phosphate Isomerase Deficiency: High Prevalence of p.Arg347His Mutation in Indian Population Associated with Severe Hereditary Non-Spherocytic Hemolytic Anemia Coupled with Neurological Dysfunction.

OBJECTIVES: Glucose-6-phosphate isomerase (GPI) deficiency is an autosomal recessive genetic disorder causing hereditary non-spherocytic hemolytic anemia (HNSHA) coupled with a neurological disorder. The aim of this study was to identify GPI genetic defects in a cohort of Indian patients with HNSHA coupled with neurological dysfunction. METHODS: Thirty-five patients were screened for GPI deficiency in the HNSHA patient group; some were having neurological dysfunction. Enzyme activity was measured by spectrophotometric method. The genetic study was done by single-stranded conformation polymorphism (SSCP) analysis, restriction fragment length polymorphism (RFLP) analysis by the restriction enzyme AciI for p.Arg347His (p.R347H) and confirmation by Sanger's sequencing. RESULTS: Out of 35 patients, 15 showed 35% to 70% loss of GPI activity, leading to neurological problems with HNSHA. Genetic analysis of PCR products of exon 12 of the GPI gene showed altered mobility on SSCP gel. Sanger's sequencing revealed a homozygous c1040G > A mutation predicting a p.Arg347His replacement which abolishes AciI restriction site. The molecular modeling analysis suggests p.Arg347 is involved in dimerization of the enzyme. Also, this mutation generates a more labile enzyme which alters its three-dimensional structure and function. CONCLUSIONS: This report describes the high prevalence of p.Arg347His pathogenic variant identified in Indian GPI deficient patients with hemolytic anemia and neuromuscular impairment. It suggests that neuromuscular impairment with hemolytic anemia cases could be investigated for p.Arg347His pathogenic variant causing GPI deficiency because of neuroleukin activity present in the GPI monomer which has neuroleukin action at the same active site and generates neuromuscular problems as well as hemolytic anemia.

Comparison of antiemetic efficacy and safety of palonosetron vs ondansetron in the prevention of chemotherapy-induced nausea and vomiting in children.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) in children is a major side effect despite the use of combination antiemetic drugs. OBJECTIVE: To compare the efficacy and safety profile of palonosetron, a second-generation 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, with ondansetron in the prevention of CINV in children. METHODS: A prospective, randomized, crossover study was conducted in patients aged 2-18 years. 160 chemotherapy cycles, consisting of chemotherapy drugs with moderate- and high-emetogenic potential, were studied. The study group received a single dose of intravenous (IV) palonosetron 5 mcg/kg, and the standard group received IV ondansetron 5 mg/m2 every 8 hours while receiving chemotherapy. The patients were observed for vomiting, use of rescue antiemetic medications, and nausea from Day 1 0-72 hours after completion of each chemotherapy cycle. All adverse events during the study period were recorded. RESULTS: The overall percentage of patients with complete response (CR) in the palonosetron and ondansetron groups were 60% and 56.2%, respectively (𝑃 = .631). The CR rates in the palonosetron and ondansetron groups were 75% and 70%, respectively, in the acute phase (𝑃 = .479), and 68.8% and 65%, respectively, in the delayed phase (𝑃 = .614). There was no statistically significant difference in the CR rates cross both groups. CONCLUSION: A single dose of palonosetron is noninferior to ondansetron in the prevention of CINV in children and can be considered as an alternative antiemetic drug. There was no significant difference in adverse effects between the palonosetron and ondansetron group.

Sevelamer Hydrochloride for Tumor Lysis Syndrome-related Hyperphosphatemia.

BACKGROUND: Tumour lysis syndrome is associated with high levels of uric acid, phosphate and potassium along with low levels of calcium and abnormal renal function. Sevelamer, an oral phosphate-binder is used in the treatment of hyperphosphatemia in children and adults on hemodialysis. CASE CHARACTERISTICS: Two children with T-cell acute lymphoblastic leukemia who presented with a high tumour load and developed tumour lysis syndrome. OBSERVATION: Both children received Rasburicase and Sevelamer hydrochloride. The serum phosphate reduced to normal levels within 24-48 hrs of initiation of sevelamer hydrochloride. MESSAGE: Sevelamer appears to be an effective treatment for hyperphosphatemia associated with tumour lysis syndrome.