A novel mutation in the glycogen synthase 2 gene in a child with glycogen storage disease type 0

<p>Abstract</p> <p>Background</p> <p>Glycogen storage disease type 0 is an autosomal recessive disease presenting in infancy or early childhood and characterized by ketotic hypoglycemia after prolonged fasting and postprandial hyperglycemia and hyperlactatemia. Sixteen different mutations have been identified to date in the gene which encodes hepatic glycogen synthase, resulting in reduction of glycogen storage in the liver.</p> <p>Case Presentation</p> <p>Biochemical evaluation as well as direct sequencing of exons and exon-intron boundary regions of the <it>GYS2 </it>gene were performed in a patient presenting fasting hypoglycemia and postprandial hyperglycemia and her parents. The patient was found to be compound heterozygous for one previously reported nonsense mutation (c.736 C>T; R243X) and a novel frameshift mutation (966_967delGA/insC) which introduces a stop codon 21 aminoacids downstream from the site of the mutation that presumably leads to loss of 51% of the COOH-terminal part of the protein. The glycemia and lactatemia of the parents after an oral glucose tolerance test were evaluated to investigate a possible impact of the carrier status on the metabolic profile. The mother, who presented a positive family history of type 2 diabetes, was classified as glucose intolerant and the father, who did not exhibit metabolic changes after the glucose overload, had an antecedent history of hypoglycemia after moderate alcohol ingestion.</p> <p>Conclusion</p> <p>The current results expand the spectrum of known mutations in <it>GYS2 </it>and suggest that haploinsufficiency could explain metabolic abnormalities in heterozygous carriers in presence of predisposing conditions.</p

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. A diagnosis of DKA is confirmed when all of the three criteria are present — ‘D’, either elevated blood glucose levels or a family history of diabetes mellitus; ‘K’, the presence of high urinary or blood ketoacids; and ‘A’, a high anion gap metabolic acidosis. Early diagnosis and management are paramount to improve patient outcomes. The mainstays of treatment include restoration of circulating volume, insulin therapy, electrolyte replacement and treatment of any underlying precipitating event. Without optimal treatment, DKA remains a condition with appreciable, although largely preventable, morbidity and mortality. In this Primer, we discuss the epidemiology, pathogenesis, risk factors and diagnosis of DKA and provide practical recommendations for the management of DKA in adults and children

Análise dos ajustes insulinoterápicos realizados a partir de dois esquemas de monitorização domiciliar em pacientes com diabetes mellitus do tipo 1 Análisis de los ajustes insulinoterápicos realizados a partir de dos esquemas de monitorización domiciliaria en pacientes con diabetes mellitus del tipo 1 Frequency and insulin adjustments among patients with type 1 diabetes mellitus

OBJETIVOS: Identificar a freqüência e magnitude nos ajustes das doses de insulina a partir de dois esquemas de monitorização domiciliar sangüíneo e urinário em pacientes com diabetes mellitus do tipo1 e avaliar a efetividade dos ajustes no controle metabólico. MÉTODOS: Amostra de 25 pacientes dividida em dois grupos. Osdo Grupo A realizaram monitorização domiciliar da glicemia capilar e osdo Grupo B, monitorização domiciliar da glicosúria, conforme esquemas preconizados. Estes esquemas possibilitaram construção de perfis e de ajustes insulinoterápicos. RESULTADOS: Houve 204 possibilidades de ajustes no Grupo A e 87 no Grupo B. Com relação às doses de insulina NPH matutina, no Grupo A foram implementados 95 (46,57%)ajustes e no Grupo B 30 (34,48%) (p= 0,03715). Os ajustes nas doses de insulina regular feitas antes do jantar também foram maiores no Grupo A ,22 (10,84%)do que no Grupo B, 3 (3,45%) (p=0,02852). O Grupo A, apresentou-se com melhor controle metabólico (HbA1c=10,17%) quando comparado ao Grupo B (HbA1c=12,31%). CONCLUSÕES: A monitorização domiciliar da glicemia, possibilitou maior número de ajustes, maior número de aplicações e melhor controle metabólico.<br>OBJETIVOS: Identificar la frecuencia y magnitud en los ajustes de las dosis de insulina a partir de dos esquemas de monitorización domiciliaria sanguíneo y urinario en pacientes con diabetes mellitus del tipo1 y evaluar la efectividad de los ajustes en el control metabólico. MÉTODOS: muestra de 25 pacientes dividida en dos grupos. Losdel Grupo A realizaron monitorización domiciliaria de la glicemia capilar y losdel Grupo B, monitorización domiciliaria de la glicosuria, conforme esquemas establecidos. Estos esquemas posibilitaron la construcción de perfiles y de ajustes insulinoterápicos. RESULTADOS: Hubo 204 posibilidades de ajustes en el Grupo A y 87 en el Grupo B. Con relación a las dosis de insulina NPH matutina, en el Grupo A fueron implementados 95 (46,57%) ajustes y en el Grupo B 30 (34,48%) (p= 0,03715). Los ajustes en las dosis de insulina regular realizadas antes de la cena fueron también mayores en el Grupo A, 22 (10,84%) que en el Grupo B, 3 (3,45%) (p=0,02852). El Grupo A, presentó mejor control metabólico (HbA1c=10,17%) que el Grupo B (HbA1c=12,31%). CONCLUSIONES: La monitorización domiciliaria de la glicemia, posibilitó un mayor número de ajustes, mayor número de aplicaciones y mejor control metabólico.<br>OBJECTIVES: To describe the frequency and effectiveness of insulin adjustments among patients with type 1 diabetes. METHODS: A sample of 25 patients was assigned to a glucose monitoring group (Group A) or to a urine monitoring group (Group B). Group A performed daily blood glucose monitoring and Group B performed daily urine glucose monitoring, according to established protocols. These protocols were used to construct patients' glycemic profile and therapeutic insulin adjustments. RESULTS: There were 204 and 87 possibilities of insulin adjustments in Group A and Group B, respectively. Group differences show that Group A performed more NPH insulin adjustments in the morning (95 adjustments [46.57%]) than Group B (30 adjustments [34.48%]) (p=0. 03715). Regular insulin adjustments before supper were also performed more by Group A, 22 adjustments (10.84%) than by Group B, 3 adjustments (3.45%) (p=0.02852). In additions, Group A showed better metabolic control (HbA1c = 10.17%) than Group B (HbA1c=12.31%). CONCLUSIONS: Home blood glucose monitoring led to greater number of adjustments, greater number of insulin injections, and better metabolic control

Mutation Analysis in Glycogen Storage Disease Type III Patients in the Netherlands:Novel Genotype-Phenotype Relationships and Five Novel Mutations in the AGL Gene

Glycogen Storage Disease type III (GSD III) is an autosomal recessive disorder in which a mutation in the AGL gene causes deficiency of the glycogen debranching enzyme. In childhood, it is characterized by hepatomegaly, keto-hypoglycemic episodes after short periods of fasting, and hyperlipidemia. In adulthood, myopathy, cardiomyopathy, and liver cirrhosis are the main complications. To determine the genotype of the GSD III patients (n = 14) diagnosed and treated in our center, mutation analysis was performed by either denaturing gradient gel electrophoresis or full gene sequencing. We developed, validated and applied both methods, and in all patients a mutation was identified on both alleles. Five novel pathogenic mutations were identified in seven patients, including four missense mutations (c.643G>A, p.Asp215Asn; c.655A>G, p.Asn219Asp; c.1027C>T, p.Arg343Trp; c.1877A>G, p.His626Arg) and one frameshift mutation (c.3911delA, p.Asn1304fs). The c.643G>A, p.Asp215Asn mutation is related with type IIIa, as this mutation was found homozygously in two type IIIa patients. In addition to five novel mutations, we present new genotype-phenotype relationships for c.2039G>A, p.Trp680X; c.753_756delCAGA, p.Asp251fs; and the intron 32 c.4260-12A>G splice site mutation. The p.Trp680X mutation was found homozygously in four patients, presenting a mild IIIa phenotype with mild skeletal myopathy, elevated CK values, and no cardiomyopathy. The p.Asp251fs mutation was found homozygously in one patient presenting with a severe IIIa phenotype, with skeletal myopathy, and severe symptomatic cardiomyopathy. The c.4260-12A>G mutation was found heterozygously, together with the p.Arg343Trp mutation in a severe IIIb patient who developed liver cirrhosis and hepatocellular carcinoma, necessitating an orthotopic liver transplantation