Red Cell Enzyme Activities Research Articles

Prevalence of Glucose 6 Phosphate Dehydrogenase Deficiency in Population of Gujarat - Report of 9184 Cases

Background: All humans have the Glucose 6 phosphate dehydrogenase gene. Some people are born with a mutation of the Glucose 6 phosphate dehydrogenase gene. Most of these individuals are asymptomatic but may exhibit non-immune hemolytic anemia, even severe anemia in response to exposure to certain environmental triggers, most commonly, infection or exposure to certain foods like fava beans (favism), medications or chemicals. G6PD deficiency is an X-linked disorder that primarily affects males. Heterozygous females do not usually develop severe hemolytic anemia due to G6PD deficiency. This study destined to reveal the prevalence of G6PD deficiency in south Gujarat population. Methods: This is a retrospective case study designed to assess the prevalence of G6PD deficiency in gujarat population, for patient requesting G6PD test at multiple collection center of Desai metropolis laboratory pvt ltd. between January 2022 to May 2023. Glucose-6-phosphate dehydrogenase deficiency analysis was done by Methylene dye blue test (Arkray MBK) – Qualitative method. All G6PD deficient patient confirmed by G6PD-quantitative (Kinetic method). Results: Total 9180 patients (5790 male and 3394 female) were included in this study. They were subsequently categorized into various subgroups and analysed properly. The incidence of G6PD deficiency in the selected sample frame of cases was 3.69 %. In which 4.11% of G6PD deficient cases belong to the male while the rest 2.98 % belong to the female. Conclusion: Therefore, to conclude whenever clinical and hematological findings raise the suspicion of glucose 6 phosphate dehydrogenase deficiency, the disorder should be confirmed by quantitative/quantitative measurement of red blood cell enzyme activity in both male and female. There is also need for a large screening programme, especially in malaria endemic zones.

Effect of Ficus carica extract on hematological parameters and antioxidant defense system in erythrocytes of albino rats exposed to nickel chloride

Heavy metals including nickel have adverse effects on hematological system and red blood cells antioxidant defense. The purpose of the study is to examine the possible corrective effect of fig (Ficus carica L.) extract (FCE) on hematological parameters and antioxidant enzyme activities in red blood cells of rats exposed to sub-lethal concentration of nickel. Male Wistar rats were exposed to nickel chloride (10 mg/kg) and then treated or no with FCE (350 mg/kg) for 4-weeks. The intoxication induces alteration of haematological parameters and enhances blood haemolysis, generates oxidative stress induced decrease in the antioxidant enzyme activities and depletion in reduced glutathione levels in intoxicated group compared to the control group. The oral administration of FCE increase significantly hemoglobin levels (Hb), red blood cells count (RBC), hematocrit (Ht) and decreases white blood cells counts (WBC), and platelets in F. carica treated groups, and also the extract increase the GSH-Px and SOD antioxidant activity, GSH reserves in red blood cells, and reduces lipids peroxidation. The present study concludes that fig fruits may exhibit potent antioxidant potential for erythrocytes and have a positive effect on hematological system.

Galactose epimerase deficiency: lessons from the GalNet registry

BackgroundGalactose epimerase (GALE) deficiency is a rare hereditary disorder of galactose metabolism with only a few cases described in the literature. This study aims to present the data of patients with GALE deficiency from different countries included through the Galactosemia Network to further expand the existing knowledge and review the current diagnostic strategy, treatment and follow-up of this not well characterized entity.MethodsObservational study collecting medical data from December 2014 to April 2022 of 22 not previously reported patients from 14 centers in 9 countries. Patients were classified as generalized or non-generalized based on their genotype, enzyme activities in different tissues and/or clinical picture and professional judgment of the treating physician.ResultsIn total 6 patients were classified as generalized and 16 as non-generalized. In the generalized group, acute neonatal illness was reported in 3, cognitive and developmental delays were present in 5 and hearing problems were reported in 3. Four generalized patients were homozygous for the genetic variant NM_001008216.2:c.280G > A (p.Val94Met). In the non-generalized group, no clearly related symptoms were found. Ten novel genetic variants were reported in this study population.ConclusionThe phenotypic spectrum of GALE deficiency ranges from asymptomatic to severe. The generalized patients have a phenotype that is in line with the 9 described cases in the literature and prescribing dietary interventions is the cornerstone for treatment. In the non-generalized group, treatment advice is more difficult. To be able to offer proper counseling, in addition to red blood cell enzyme activity, genetic studies, transferrin glycoform analysis and enzymatic measurements in fibroblasts are recommended. Due to lack of facilities, additional enzymatic testing is not common practice in many centers nor a tailored long-term follow-up is performed.

The Use of Next-generation Sequencing in the Diagnosis of Rare Inherited Anaemias: A Joint BSH/EHA Good Practice Paper.

The Use of Next-generation Sequencing in the Diagnosis of Rare Inherited Anaemias: A Joint BSH/EHA Good Practice Paper.

Exposure to Azathioprine Metabolites and Clinical Outcome in Indian Patients with Crohn’s Disease

Aim: To determine the concentration of 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP), the interpatient variability, and the relationship with disease activity in patients with Chron’s disease on long-term stable doses of azathioprine (AZA). Methods: This is a prospective, tertiary care single-center hospital study in adult Chron’s disease patients treated with AZA. The quantification of phenotypic thiopurine methyltransferase enzyme activity in red blood cells and the estimation of the concentration of 6-TGN and 6-MMP in whole blood was performed using the HPLC-UV detector method. A clinical response was categorized as remission (Harvey-Bradshaw Index [HBI] < 5) or improvement (drop from baseline of at least three points of HBI) based on HBI. Exposure to metabolite concentrations and the clinical response to AZA treatment was observed. Results: Study analysis included 30 patients who were initiated on AZA, and they were followed up with an estimation of metabolite concentrations to determine their clinical outcome. At six months, 93% of ( n = 28) patients continued to be on AZA and had clinical improvement. All the patients achieved remission of Chron’s disease. Only two patients developed adverse effects such as joint pain and thrombocytopenia. Conclusion: AZA is a safe and effective therapy in managing Chron’s disease when administered after determining thiopurine methyltransferase phenotype and with dose optimization performed using therapeutic drug monitoring of 6-TGN and 6-MMP.

Haematological Indices and Antioxidant Enzyme Activity in Ghanaian Stroke Patients.

Background Stroke is a cardiovascular disorder causing mortality globally and long-lasting harm worldwide. The disease occurs when the blood flow to the brain is either interrupted or blocked. This disruption leads to the increase in reactive oxygen species (ROS), especially superoxide free radicals, resulting in oxidative stress. The superoxide radicals are removed by superoxide dismutase (SOD), a key antioxidant enzyme. In this work, we investigated haematological indices and superoxide dismutase enzyme activity in Ghanaian patients with stroke and healthy control participants. Materials and Methods Thirty stroke patients attending a stroke clinic and thirty apparently healthy control participants were recruited into the study. Blood samples were collected to determine haematological indices and SOD enzyme activity in red blood cells. Results The stroke patients had significantly high blood parameters such as white blood cell (p < 0.001), neutrophil (p < 0.001), lymphocyte (p = 0.003), and eosinophil (p < 0.001) comparing with study participants without stroke, who were the control group in the study. Other blood parameters such as red blood cell, (p < 0.001), haemoglobin (p < 0.001), and haematocrit (p < 0.001) levels and mean cell haemoglobin concentration (p = 0.030), platelet (p = 0.010), and plateletcrit (p = 0.027) were high in stroke patients comparing with study control participants and statistically significant. Blood lymphocyte levels observed in stroke patients correlated negatively and significantly with SOD activity levels. SOD activity levels were significantly lower in stroke patients compared with the control group (p < 0.001). Low values of the antioxidant enzyme SOD activity levels, lymphocytes, and high values of plateletcrit were significant predictors of stroke. Conclusion Haematological parameters such as WBC, lymphocyte, platelet levels, and red cell indices were significantly different in the stroke patients being studied. There was negative correlation between lymphocyte significantly with SOD activity and high oxidative stress in stroke patients compared with the control group. Lymphocytes and plateletcrit levels were also good predictors of the occurrence of stroke.

Clinical, laboratory, and mutational profile of children with glucose phosphate isomerase deficiency: a single centre report.

Glucose phosphate isomerase (GPI) deficiency is an autosomal recessive condition with mutations in the GPI gene on chromosome 19q13.1. Patients present with congenital non-spherocytic hemolytic anemia, and occasionally intellectual disability. In this study, we describe the clinical, hematological and biochemical parameters in the largest single-center cohort consisting of 17 GPI-deficient cases. Demographic and clinical data were noted, and red cell enzyme activity levels were estimated. Mutation analysis was done by single-stranded-conformation polymorphism, restriction-fragment length polymorphism and Sanger's sequencing of exon 12 of the GPI gene. The male-to-female ratio was 0.7:1, median age at diagnosis was 5.0years, 82.3% of patients had severe neonatal jaundice, and 13.3% had subtle neurological manifestations. Median Hb and MCV levels were 6.3g/dl and 130.2fl. Splenectomized patients required fewer transfusions. Sixteen of 17 patients had the pathogenic c.1040G > A (p.Arg347His) homozygous mutation in exon12 of the GPI gene, and one had the pathogenic c.1414C > T(p.Arg472Cys) homozygous mutation in exon 16. In summary, we report that neonatal jaundice, macrocytosis and high prevalence of p.Arg347His variant were predominant in GPI deficiency with prominent lack of neurological manifestations, and we emphasize the benefits of splenectomy and the need for genetic counseling.

Обеспеченность витаминами В1, В2 организма коренных северян, ведущих полукочевой и оседлый образ жизни

The Komi Republic is one of the regions with large communities of reindeer herders. As a result of the active development of northern territories, the indigenous population is shifting from nomadic to sedentary lifestyle, which is accompanied by significant changes in their traditional way of life and diet. As a result, representatives of the same ethnic group can have different dietary patterns. This paper compares the status of vitamins B1 and B2 between the groups of northerners leading a seminomadic and sedentary lifestyle. Indigenous inhabitants – children (aged 7–17 years, n = 395) and adults (aged 18–57 years, n = 370) – living in the Komi Republic (65–67°N) were examined. The group of reindeer herders consisted of workers of reindeer-herding teams travelling with the herd and their children (either attending boarding schools or living with their families). The control group was represented by indigenous northerners not involved in reindeer herding and permanently living in settlements. The vitamins B1 and B2 status was measured by the activity of vitamin-dependent red cell enzymes. We found a high prevalence of vitamin deficiency (over 40 % for vitamin B1 and over 30 % for vitamin B2) among the indigenous population of the North. The total prevalence of vitamin deficiency among reindeer herders was similar to that in the population leading a sedentary lifestyle; however, severe hypovitaminosis was more than twice as common among the latter. The vitamin status of reindeer herders’ children attending boarding schools and those living with their families during the academic year did not differ significantly from the status of children whose families lead a permanent sedentary lifestyle.

Effect of Astaxanthin on Antioxidant Enzyme Activities in Suspended Leukocyte-Depleted Red Blood Cells Stored for Transfusion

To observe the effect of astaxanthin (ASTA) on the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in suspended leukocyte-depleted red blood cells stored for transfusion. The suspended leukocyte-depleted red blood cells were randomly divided into group A, B, C and D. The ASTA was added into preservation solution of suspended leukocyte-depleted red blood cells of group B, C and D with the final concentration 5, 10 and 20 μmol/L, respectively, while DMSO was added into cells of group A in the same volume. After 7, 14, 28 and 42 days of storage, the reactive oxygen species (ROS) content in red blood cells was detected by fluorescence microplate reader, malondialdehyde (MDA) content was detected by thiobarbituric acid (TBA) method, activity of SOD was detected by xanthine oxidase method, the activity of CAT was detected by visible light method, and activity of GSH-Px was detected by colorimetry. After 7, 14, 28 and 42 days of storage, the contents of ROS and MDA in suspended red blood cells of group B, C and D were significantly lower(P<0.05), while the activities of SOD and GSH-Px were higher than those of group A(P<0.05); and CAT activity in cells treated by ASTA was significantly higher at 28 and 42 days of storage in comparison with that of group A(P<0.05). There were positive correlations between the ROS, MDA content in suspended red blood cells of group A, B, C, D and storage time(P<0.01), while negative correlation between SOD, CAT, GSH-Px activity and storage time(P<0.01). ASTA can decrease the oxidative stress level and peroxide damage degree by increasing the antioxidant enzyme activities in suspended leukocyte-depleted red blood cells during storage.

A RARE CAUSE OF NEONATAL CYANOSIS - CONGENITAL METHEMOGLOBINEMIA — A CASE REPORT

Cyanosis can occur at any age but it is a great challenge when it is in the newborn. Multiple causes have been established, and it usually is an ominous sign, especially when it occurs with neonatal sepsis or cyanotic congenital heart disease. Cyanosis caused by abnormal forms of hemoglobin can be life threatening, and early recognition is mandatory to prevent unnecessary investigations and delay in management. Abnormal hemoglobin newborn screening is a useful tool for the diagnosis. Acquired methemoglobinemia caused by environmental oxidizing agents, is common, but congenital deficiency of the innate reducing enzyme is so rare that only a few cases are documented in the medical literature around the world. Here I am presenting a case of a neonate with cyanosis as a result of congenital deficiency of cytochrome b5 reductase enzyme. This neonate was found to have cyanosis and appeared blue at newborn follow-up visit. Sepsis, congenital heart disease, prenatal administration, and ingestion of oxidant dyes were excluded as causes of the cyanosis by history, examination and appropriate tests. Chocolate discoloration of arterial blood provided a clue to the diagnosis. A normal newborn screen and hemoglobin electrophoresis made the diagnosis of hemoglobin M unlikely as the cause of the methemoglobinemia (Hb A 58.9%, A2 1.9%, and F 39.2%). Red blood cell enzyme activity and DNA analysis revealed a homozygous form of the cytochrome b5 reductase enzyme deficiency. She responded very well to daily methylene blue and ascorbic acid administration, and she has normal growth and developmental parameters, although she shows an exaggerated increase in her methemoglobin level.

Impact of Next-Generation Sequencing on the Diagnosis and Treatment of Congenital Anemias.

Congenital anemias are a wide spectrum of diseases including hypoproliferative anemia syndromes, dyserythropoietic anemias, sideroblastic anemias, red blood cell membrane and enzymatic defects, hemoglobinopathies, and thalassemia syndromes. The various congenital anemia syndromes may have similar clinical and laboratory presentations, making the diagnosis challenging. The traditional work-up, which includes a complete blood count, blood smears, bone marrow studies, flow cytometry, and the osmotic fragility test, does not always lead to the diagnosis. Specialized tests such as red blood cell enzyme activity and ektacytometry are not widely available. In addition, red blood cell transfusions may mask some of the laboratory characteristics. Therefore, genetic testing is crucial for accurate diagnosis of patients with congenital anemias. However, gene-by-gene testing is labor intensive because of the large number of genes involved. Thus, targeted next-generation sequencing using custom-made gene panels has been increasingly utilized, with a high success rate of diagnosis. Accurate genetic diagnosis is important for determining specific therapeutic modalities, as well as for avoiding splenectomy when contraindicated. In addition, molecular diagnosis can allow for genetic counseling and prenatal diagnosis in severe cases. We suggest a work-up scheme for patients with congenital anemias, including early incorporation of targeted next-generation sequencing panels.

Biochemical features of primary cells from a pediatric patient with a gain-of-function ODC1 genetic mutation.

We recently described a new autosomal dominant genetic disorder in a pediatric patient caused by a heterozygous de novo mutation in the ornithine decarboxylase 1 (ODC1) gene. The new genetic disorder is characterized by global developmental delay, alopecia, overgrowth, and dysmorphic features. We hypothesized that this new mutation (c.1342 A>T) leads to a C-terminal truncation variant of the ODC protein that is resistant to normal proteasomal degradation, leading to putrescine accumulation in cells. ODC (E.C. 4.1.1.17) is a rate-limiting enzyme in the biosynthesis of polyamines (putrescine, spermidine, and spermine) that plays a crucial role during embryogenesis, organogenesis, and tumorigenesis. In this study, we show that primary dermal fibroblasts derived from a skin biopsy of a 3-year-old patient contain large amounts of ODC protein and putrescine compared with primary dermal (neonatal and adult) fibroblast control cells. Importantly, the accumulated ODC protein variant remained functionally active as we detected exceptionally high ODC enzyme activity in both primary dermal fibroblasts (12-17-fold of controls) and red blood cells (RBCs) (125-137-fold of controls), using a specific 14C radioactive ODC activity assay. Exposure of primary dermal fibroblasts to ODC inhibitor α-difluoromethylornithine (DFMO) reduced the ODC activity and putrescine to levels observed in controls without adversely affecting cell morphology or inducing cell death. In conclusion, our patient and potentially other patients that carry a similar ODC1 gain-of-function mutation might benefit from treatment with DFMO, a drug with a good safety profile, to suppress the exceptionally high ODC activity and putrescine levels in the body.

Red cell adenylate kinase deficiency in India: identification of two novel missense mutations (c.71A>G and c.413G>A)

Adenylate kinase (AK) deficiency is a rare erythroenzymopathy associated with hereditary nonspherocytic haemolytic anaemia along with mental/psychomotor retardation in few cases. Diagnosis of AK deficiency depends on the decreased level...

Bone marrow transplantation corrects haemolytic anaemia in a novel ENU mutagenesis mouse model of TPI deficiency.

ABSTRACTIn this study, we performed a genome-wide N-ethyl-N-nitrosourea (ENU) mutagenesis screen in mice to identify novel genes or alleles that regulate erythropoiesis. Here, we describe a recessive mouse strain, called RBC19, harbouring a point mutation within the housekeeping gene, Tpi1, which encodes the glycolysis enzyme, triosephosphate isomerase (TPI). A serine in place of a phenylalanine at amino acid 57 severely diminishes enzyme activity in red blood cells and other tissues, resulting in a macrocytic haemolytic phenotype in homozygous mice, which closely resembles human TPI deficiency. A rescue study was performed using bone marrow transplantation of wild-type donor cells, which restored all haematological parameters and increased red blood cell enzyme function to wild-type levels after 7 weeks. This is the first study performed in a mammalian model of TPI deficiency, demonstrating that the haematological phenotype can be rescued.

Molecular basis of pyruvate kinase deficiency among Tunisians: description of new mutations affecting coding and noncoding regions in the PKLR gene.

Pyruvate kinase (PK) deficiency is one of the most common hereditary nonspherocytic hemolytic anemias worldwide with clinical manifestations ranging from mild to severe hemolysis. However, investigation of this enzymopathy is lacking in Tunisia. We report here a pioneer investigation of PK deficiency among Tunisian cases referred to our laboratory for biological analysis of unknown cause of hemolytic anemia. Two hundred and fifty-three patients with unknown cause of hemolytic anemia have been addressed to our laboratory in order to investigate for red blood cells genetic disorders. Red cell enzyme activities were measured by standard methods, and molecular analysis was performed by DNA sequencing. The interpretation of mutation effect and the molecular modeling were performed by using specific software. Six different PKLR mutations were found (c.966-1G>T; c.965+1G>A; c.721G>T; c.1163C>A; c.1456C>T; c.1537T>A), among which four are described for the first time. Genotype-phenotype correlations for the novel missense mutations were investigated by three-dimensional structure analysis. This study provides important data of PK deficiency among Tunisians. It might be followed by a large neonatal screening to determine the spectrum of PK mutations and identify potential deficient patients for an early medical follow-up.

The Novel Missense Mutation of GATA1 Caused Red Cell Adenosine Deaminase Overproduction Associated with Congenital Hemolytic Anemia

Red cell adenosine deaminase (ADA) overproduction (OMIM 102730) is a rare form of congenital hemolytic anemia. To date, only four independent families have been reported. Recently, we examined the red cell enzyme activities of an 18-year-old male Japanese patient with congenital hemolytic anemia, and diagnosed a new case of ADA overproduction. His ADA activity was measured as 39.7 IU/gHb, representing an over 30-fold elevation of the normal mean value. The patient’s mother also showed a high red cell ADA, 7.40 IU/gHb, and the father had normal ADA activity. To elucidate the molecular basis of the elevated ADA activity, we performed a target-captured sequencing focusing on the 67 congenital-anemia related genes. The results showed that there was no structural mutation of ADA gene, and that the proband had a novel missense mutation of GATA1, c.920G>A, p.R307H. The proband was hemizygous, and the mother was heterozygous for the mutation. Subsequently, we examined a previously reported case of ADA overproduction, and identified the identical missense mutation of GATA1. These two cases had clinical similarities, such as low birth weight with hypospadias, splenomegaly, and slightly decreased platelet counts, suggesting that these cases could be categorized as X-linked anemia with or without neutropenia and/or platelet abnormality (XLANP, OMIM#300835). The previous case showed a rare blood type, Lu(a-b-) and a low beta/alpha globin synthetic ratio, whereas the present case depicted abnormal red cell morphology, such as stomatocytosis and target cells. Taken together, the missense mutation of GATA1 might cause the aberrant expression of erythroid-genes, inducing a short life-span of red cells. DisclosuresNo relevant conflicts of interest to declare.

Clinical observation over the dynamic of the intrauteral mixed infection in the child of early age

Difficulty in diagnosis of the intrauterine infections (IUI) is associated with the low specificity of clinical manifestations and the multiple organ injury, prolonged persistence of the pathogen in the body, a significant prevalence of mixed infections and their frequent combination with the somatic disorders in newborns. The clinical case of mixed intrauterine infection in the child of early age is presented. The full-term boy was under the observation, he was born with severe anemic syndrome, indirect hyperbilirubinemia and hepatosplenomegaly. According to clinical observation and ultrasound of the abdomen the size of his liver and spleen increased progressively for six days after birth, it was accompanied by dynamic increase of total bilirubin due to its direct fraction, decrease of platelets count. ELISA-diagnostics of the child’s serum revealed the presence of the anti-toxoplasma and anti-cytomegalovirus antibodies. Taking into account obtained clinical and paraclinical data, the newborn child was diagnosed with intrauterine mixed infection with primary hematopoietic and liver damage (cholestatic-cytolytic variant). Anti-toxoplasma immunoglobulin was administered to child, but because of severe liver injury specific causal treatment of toxoplasmosis was postponed due to its hepatotoxicity. Later on anemic syndrome with indirect hyperbilirubinemia recurrently repeated in a child, it was dependent on transfusions but refractory to treatment. The presence of DNA of CMV and herpes virus type 6 was confirmed by PCR in the dynamic study of the five-month old child’s blood. Taking into account the obtained results of the examination, the child was diagnosed with severe congenital cytomegalovirus infection in the replication phase and comorbid congenital nonspherocytic hemolytic anemia of unknown origin with continuous crisis. The patient received anti-cytomegalovirus ganciclovir intravenously, antiherpetic valaciclovir orally. As a result of the treatment positive clinical dynamics was observed, which was accompanied by a decrease of the hepatolienal syndrome and gaining weight, but multiple red blood cell transfusions were not accompanied by significant or prolonged rise in hemoglobin levels. After the treatment twice done PCR child’s blood tests for CMV DNA were negative. Taking into account the crisis duration of the disease, splenectomy was discussed. The clinical case refers to the rare clinical diagnostic situations in medical practice when it is difficult to make a final conclusion about the etiology of the IUI. Verification of the intrauterine mixed infection was problematic in the neonatal period and during follow-up. The complexity of the diagnostic process was caused by the absence of the typical neurological symptoms. The diagnosis of mixed IUI was complicated by coexistence of the congenital nonspherocytic hemolytic anemia, the genesis of which could not be set, despite the study of enzyme activity in red blood cells, assessment of their osmotic resistance and Coombs tests. Damage of the erythroid stem hematopoiesis probably was caused by the infectious factors during the intrauteral period as well as by the hereditary pathology of the erythron.

Mutual Interactions among Anti‐oxidative Nutrients, Antioxidant Enzymes and Urinary Biomarkers of Oxidative Stress in Guatemalan Preschoolers in the Western Highlands

Background The harmonization of action of enzymes and non-enzymatic compounds is poorly understood. Objective To explore interaction among enzymatic and nutrient markers of the antioxidant defense system in blood with urinary biomarkers of oxidative stress in low-income Guatemalan children consuming a common menu offering. Methods: Whole blood and 24-h urines were collected from 82 children, 2-7y, from the Western Highlands. Urinary oxidative stress biomarkers included F2-isoprostanes (F2-Iso) and 8-OHdG. Red cell enzyme activities were: catalase; superoxide dismutase; glutathione peroxidase and glutathione reductase. Circulating antioxidant nutrients included: retinol, α-tocopherol, β-carotene and coenzymes Q9 and Q10. Results: 28 (51%) of 55 paired combinations of the 11 biomarkers were significantly and mutually correlated (p蠄0.05), most strongly between retinol and α-tocopherol (r=0.697, p<0.001). F2-Iso showed the greatest number of cross-associations, having significant interactions with 8 of the 10 remaining biomarkers. Backward-elimination multiple regression indicated that plasma retinol, β-carotene and coenzyme Q10 were independent predictors of urinary F2-Iso. Conclusions The antioxidant enzymes and antioxidant nutrient mitigation of oxidative stress works in concert to deal with daily life prooxidative challenges. Funding: Hildegard Grunow Foundation.

Novel GALT variations and mutation spectrum in the Korean population with decreased galactose-1-phosphate uridyltransferase activity.

BackgroundClassic galactosemia (OMIM #230400) is an autosomal recessive metabolic disorder caused by a deficiency of the galactose-1-phosphate uridyltransferase (GALT, EC2.7.7.12) protein due to mutations in the GALT gene. The aim of this study was to provide a comprehensive and updated mutation spectrum of GALT in a Korean population.MethodsThirteen unrelated patients screened positive for galactosemia in a newborn screening program were included in this study. They showed a reduced GALT enzyme activity in red blood cells. Direct sequencing of the GALT gene and in silico analyses were done to evaluate the impact of novel variations upon GALT enzyme activity. We also reviewed previous reports for GALT mutations in Koreans.ResultsWe identified six novel likely pathogenic variations including three missense (p.Ala101Asp, p.Tyr165His, and p.Pro257Thr), one small deletion/insertion [c.826_827delinsAA (p.Ala276Asn)], one frameshift (p.Asn96Serfs*5), and one splicing (c.378-1G > C) likely pathogenic variations. The most frequent variation was the Duarte variant (c.940A > G, 35.3%), followed by c.507G > C (p.Gln169His, 9.6%), among 34 Korean patients. Other mutations were widely scattered. None of the eight common mutations used for targeted mutation analysis in Western countries including p.Gln188Arg, p.Ser135Leu, p.Lys285Asn, p.Leu195Pro, p.Tyr209Cys, p.Phe171Ser, c.253-2A > G, and a 5 kb deletion, had been found in Koreans until this study.ConclusionsConsidering the mutation spectrum in Koreans, direct sequence analysis of entire GALT exons is recommended for accurate diagnosis. The mutations responsible for GALT deficiency in the Korean population were clearly different from those of other populations.

Effect of HIV Infection and Antiretroviral Therapy on Some Red Cell Enzyme Activities and Coagulation Parameters

Aim: To assess G-6-PD, Pyruvate kinase enzyme activity and some coagulation parameters in HIV positive patients on antiretroviral treatment (ART) and those not on antiretroviral treatments with varying durations of infection and Antiretroviral treatments. Study Design: Case-control study Place and Duration of Study: Nnamdi Azikiwe University Teaching Hospital Nnewi, Nigeria from March to August 2013. Methodology: We included 181 subjects; Sixty HIV patients on ART with infection and ART duration of 5 – 8 and >8 – 17 years; Sixty HIV patients not on ART with an infection duration of 3 – 6 and >6 – 11 years; and Sixty-one apparently healthy individuals control. Glucose-6-Phosphate Dehydrogenase (G-6-PD) activity, Pyruvate kinase (PK) activity, Activated Partial Thromboplastin time (APTT), Prothrombin time