Classic galactosemia: features of diagnosis and treatment

Background. Galactosemia type I, or classic galactosemia (CG), is the most severe form of hereditary disorders of carbohydrate metabolism, in particular, galactose. Galactosemia is not included in the program of massive neonatal screening in Ukraine. The CG is characterized by the non-specific onset symptoms and leads to high mortality among infants in the neonatal period. The problem of early diagnosis and treatment of infants with CG in the absence of a program for massive neonatal screening in Ukraine requires solution. The purpose was to analyse the clinical and laboratory, molecular genetic features of patients with CG; to define a set of clinical symptoms and to form selective groups of patients for administration of diet therapy and laboratory diagnosis; to develop schemes-stages of effective early diagnosis and treatment of patients with CG in the absence of mass neonatal screening in order to reduce infant mortality and prevent the disability of patients with this pathology. Materials and methods. In 2014–2017, 317 patients with a diagnosis of hepatitis of uncertain origin were examined. The age of patients ranged from 3 days to 16 years; 145 (45 %) of them were males, 172 (55 %) — females. In all patients, a polysyndromic clinical picture with predominant lesion in the liver function was observed. All patients were examined for the activity of galactose-1-phosphate uridylyltransferase (GALT) enzyme in the red blood cells and underwent DNA diagnosis for the detection of major mutations in the GALT gene. All patients were examined for viral hepatitis, underwent biochemical blood tests for hepatic transaminases, alkaline phosphatase, bilirubin levels, and coagulopathy. Tandem mass spectrometry was also performed to exclude or confirm the metabolic imbalance of amino acids, organic acids, and mitochondrial beta-oxi­dation of fatty acids. Five patients with suspected glycogenosis have been subjected to a quantitative glycogen test in the liver biopsy sample. Results. The diagnosis of CG was established in 15 (5 %) of 317 patients. Male/female ratio was 9 : 6, patient’s age ranged from 14 days to 15 years at the time of investigation in the Center. In 13 out of 15 children, the clinical diagnosis of CG was made on average of 47 days of life (47 ± 15 days). In two patients, the CG was diagnosed at the age of 2 and 15 years. In all patients, the activity of GALT enzyme in erythrocytes was reduced and ranged from 0.08 to 5.8 U/g Hb (mean value 3.3 ± 1.6 U/g Hb) at a normal value > 10 U/g Hb. Molecular genetic analysis was performed in 14 patients. Five patients had a homozygous genotype of Q188R, 1 patient — homozygous K285N genotype, 6 patients were heterozygotes in two major mutations, Q188R and K285N (genotype Q188R/K285N); one patient had р.Y209S/р.K285N genotype, another one — р.K285N mutation only in one allele. Thus, 28 alleles in the GALT gene were examined from 14 patients and 27 mutations were identified: Q188R —57 %, K285N — 36 %, Y209S — 3 % (detected in one patient in one allele). The mutations Q188R and K285N together amounted to 93 % indicating a high level among Ukrainian population. Cataract has been diagnosed in 6 patients (40 %). In our group of CG patients, in all of them it was combined with neurological symptoms. Defeats of the nervous system (cognitive deficiency, spastic tetraparesis, dystonia, tremor and disorders in the form of dysarthria and delayed speech development) were noted in 7 CG patients (47 %). The analysis of the mortality in this group showed that it was 27 % (4 of 15 patients dead at the age of 24 days to 2.5 months). Additionally, the analysis of families with CG patients showed frequent cases of early death from liver failure in the age up to 14 weeks. In three families, there were four deaths in the neonatal period. If we consider all dead children with similar symptoms in the families with CG patients, then the percentage of deceased patients would be 47 % (8 of 19 children born in families with CG). In all cases, treatment was started too late, on average on day 44. Jaundice was observed in 93 % of CG patients, hepatomegaly — in 80 %, dyspeptic manifestations — in 87 %. The scheme has been proposed of stages of diagnostic and therapeutic measures in the selective group with suspected CG. Conclusions. CG is a life-threatening disease characterized by severe hepatocellular lesions, dyspeptic syndrome, sepsis, and high mortality in the neonatal period. Mutations Q188R and K285N together make up 93 % that indicates a high level in Ukraine. All infants with jaundice due to hyperbilirubinemia, hepatomegaly, dyspeptic disorders, high levels of transaminases, and blood clotting disorders should be screened for the presence of CG and urgently change the diet to lactose-free one, until the results of the confirmatory laboratory diagnosis are obtained

Methylovirgula ligni gen. nov., sp. nov., an obligately acidophilic, facultatively methylotrophic bacterium with a highly divergent mxaF gene

Two strains of Gram-negative, aerobic, non-pigmented, non-motile, rod-shaped bacteria were isolated from beech wood blocks during decay by the white-rot fungus Hypholoma fasciculare (Folman et al., 2008) and were designated strains BW863T and BW872. They are capable of methylotrophic growth and assimilate carbon via the ribulose-bisphosphate pathway. In addition to methanol, the novel isolates utilized ethanol, pyruvate and malate. Strains BW863T and BW872 are obligately acidophilic, mesophilic organisms capable of growth at pH values between 3.1 and 6.5 (with an optimum at pH 4.5-5.0) and at temperatures between 4 and 30 °C. Phospholipid fatty acid profiles of these bacteria contain unusually high amounts (about 90%) of 18:17c fatty acid, thereby resembling the profiles of Methylobacterium strains. The predominant quinone is Q-10. The DNA G+C content of novel isolates is 61.8-62.8 mol %. On the basis of 16S rRNA gene sequence identity, strains BW863T and BW872 are most closely related to the acidophilic methanotroph Methylocapsa acidiphila B2 (96.5-97 %). Comparative sequence analysis of mxaF, the gene encoding the large subunit of methanol dehydrogenase, placed the MxaF sequences of two novel strains in a cluster that is distinct from all previously described MxaF sequences of cultivated methylotrophs. The identity values between the MxaF sequences of the acidophilic isolates and the MxaF sequences from known alpha-, beta- and gammaproteobacterial methylotrophs comprised 69-75%, 61-63% and 64-67%, respectively. The data therefore suggest that strains BW863T and BW872 represent a novel genus and species of methylotrophic bacteria; the name Methylovirgula ligni gen. nov., sp. nov. is proposed, with strain BW863T (=DSM 19998T = NCIMB 14408T) as the type strain.

Modeling and experimental research of measuring channels characteristics using of virtual stands

У статті розглянуті питання розробки програмних моделей у середовищі графічного програмування LabView, необхідних при побудові віртуальних лабораторних стендів для дослідження метрологічних характеристик каналів інформаційно-вимірювальних систем. Представлено віртуальні прилади для експериментального дослідження характеристик вимірювального каналу гідротранспортної системи гірничометалургійного комбінату, а також для виконання комплектної та поелементної перевірок вимірювальних каналів методами зразкової міри та зразкового приладу.В статье рассмотрены вопросы разработки программных моделей в среде графического программирования LabView, необходимых при построении виртуальных лабораторных стендов для исследования метрологических характеристик информационно-измерительных систем. Представлены виртуальные приборы для экспериментального исследования характеристик измерительного канала гидротранспортной системы горно-металлургического комбината, а также для выполнения комплектной и поэлементной проверок измерительных каналов методами образцовой меры и образцового прибора.In article there are considered working out questions of program models in the graphical programming environment LabView wich are necessary to creation virtual laboratory stands for metrological characteristics of information-measuring systems. Virtual devices for an experimental research of the measuring channel characteristics for hydrotransport system of miningconcentrating plant, and also for performance of complete and bit-by-bit checks of measuring channels by methods of exemplary measure and exemplary device are presente