ABSTRACT
Pyruvate kinase deficiency is a chronic illness with age specific consequences. Newborns suffer life-threatening hemolytic crisis and hyperbilirubinemia. Adults are at risk for infections because of asplenia, pregnancy-related morbidity, and may suffer organ damage because of systemic iron overload. We describe 27 Old Order Amish patients (ages 8 months-52 years) homozygous for c.1436G>A mutations in PKLR. Each subject had a predictable neonatal course requiring packed red blood cell transfusions (30 ± 5 mL/kg) to control hemolytic disease and intensive phototherapy to prevent kernicterus. Hemochromatosis affected 29% (n = 4) of adult patients, who had inappropriately normal serum hepcidin (34.5 ± 12.7 ng/mL) and GDF-15 (595 ± 335pg/mL) relative to hyperferritinemia (769 ± 595 mg/dL). A high prevalence of HFE gene mutations exists in this population and may contribute to iron-related morbidity. Based on our observations, we present a strategy for long-term management of pyruvate kinase deficiency.
Subject(s)
Amish , Erythrocytes/enzymology , Pyruvate Kinase/deficiency , Adolescent , Adult , Anemia, Hemolytic/blood , Anemia, Hemolytic/enzymology , Anemia, Hemolytic/genetics , Child , Child, Preschool , Cohort Studies , Disease Management , Female , Humans , Infant , Longitudinal Studies , Male , Middle Aged , Pennsylvania , Pregnancy , Pyruvate Kinase/blood , Pyruvate Kinase/genetics , Risk Factors , Young AdultABSTRACT
The role of glutathione peroxidase in the oxidative metabolism and recent advances in the demonstration of the consequences of the desequilibrium in the proxidant/antioxidant balance on biological molecules oxidation, intracellular signals transduction, apoptosis and necrosis, have led to new approach in the knowledge of many pathological processes. Methods for determining antioxidant capacity have been developed. The measurement of glutathione peroxidase activity is a key step in the study of oxidative stress. Its determination in clinical biology needs optimal conditions for standardised assays which will be used for epidemiological studies aimed to evaluate the role of nutritional factors involved in the pathogeny of diseases caused or accompanied by oxidative stress.