Novel mutations associated with pyruvate kinase deficiency in Brazil.

BACKGROUND: Pyruvate kinase deficiency is a hereditary disease that affects the glycolytic pathway of the red blood cell, causing nonspherocytic hemolytic anemia. The disease is transmitted as an autosomal recessive trait and shows a marked variability in clinical expression. This study reports on the molecular characterization of ten Brazilian pyruvate kinase-deficient patients and the genotype-phenotype correlations. METHOD: Sanger sequencing and in silico analysis were carried out to identify and characterize the genetic mutations. A non-affected group of Brazilian individuals were also screened for the most commonly reported variants (c.1456C>T and c.1529G>A). RESULTS: Ten different variants were identified in the PKLR gene, of which three are reported here for the first time: p.Leu61Gln, p.Ala137Val and p.Ala428Thr. All the three missense variants involve conserved amino acids, providing a rationale for the observed enzyme deficiency. The allelic frequency of c.1456C>T was 0.1% and the 1529G>A variant was not found. CONCLUSION: This is the first comprehensive report on molecular characterization of pyruvate kinase deficiency from South America. The results allowed us to correlate the severity of the clinical phenotype with the identified variants.

Novel mutations associated with pyruvate kinase deficiency in Brazil

Abstract Background: Pyruvate kinase deficiency is a hereditary disease that affects the glycolytic pathway of the red blood cell, causing nonspherocytic hemolytic anemia. The disease is transmitted as an autosomal recessive trait and shows a marked variability in clinical expression. This study reports on the molecular characterization of ten Brazilian pyruvate kinase-deficient patients and the genotype-phenotype correlations. Method: Sanger sequencing and in silico analysis were carried out to identify and characterize the genetic mutations. A non-affected group of Brazilian individuals were also screened for the most commonly reported variants (c.1456C>T and c.1529G>A). Results: Ten different variants were identified in the PKLR gene, of which three are reported here for the first time: p.Leu61Gln, p.Ala137Val and p.Ala428Thr. All the three missense variants involve conserved amino acids, providing a rationale for the observed enzyme deficiency. The allelic frequency of c.1456C>T was 0.1% and the 1529G>A variant was not found. Conclusion: This is the first comprehensive report on molecular characterization of pyruvate kinase deficiency from South America. The results allowed us to correlate the severity of the clinical phenotype with the identified variants.

Oral lesions associated with hydroxyurea treatment.

Hydroxyurea (HU) is an antimetabolic agent commonly used in myeloproliferative disorders and hematological diseases as well as in severe psoriasis. Despite of usually be well tolerated, sometimes it can induce immunosuppression and mucocutaneous adverse effects associated with discomfort or pain. Nevertheless, oral mucosal adverse reactions are extremely uncommon and present as ulcers, tongue depapilation and dyschromia. Complete remission of adverse effects is usually observed after withdrawal of the medication. The aim of this paper is to report two patients with oral lesions related to HU treatment. T0 he patients were adequately managed by changing hydroxyurea with imatinib mesilate. Oral lesions are rare complications of long-term hydroxyurea treatment and may be an indication of stopping therapy and substitution with imatinib mesilate.

Neutropenic enterocolitis in children and young adults with cancer: prognostic value of clinical and image findings.

Intensive chemotherapy regimens can result in severe toxicities, particularly those that involve the digestive systems, leading to morbidity and mortality in this group of patients. Acute enterocolitis can be a frequent complication. The authors performed a retrospective review or patients treated at their institution to ascertain the prognostic value of the clinical symptoms and signs of acute enterocolitis, the corresponding abdominal ultrasonographic findings, and the impact of previous chemotherapy. Amongst 1159 patients with cancer treated at the Centro Infantil Boldrini from 2003 to 2007, 188 (16.2%) patients had 1 or more episode of enterocolitis. An intestinal wall thickness of >or=3 mm on ultrasound was considered diagnostic of enterocolitis. There were 231 episodes of enterocolitis with a death rate of 11.7%. Previous therapy with cytarabine and the presence of abdominal distention affected survival. An intestinal wall thickness of >or=10 mm in the ultrasonographic examination was associated with greater mortality. In multivariate analysis, age, gender, tumor type, degree of neutropenia, intestinal wall thickness, and number of intestinal segments were not statistically significant difference. In children and young adults with cancer and enterocolitis, the clinical findings of 4 or more symptoms and presence of abdominal distention were associated with higher risk of death. Use of cytarabine and an intestinal wall thickness of >or=10 mm were associated with a higher death rate.