The multiple faces of urinary glucose tetrasaccharide as biomarker for patients with hepatic glycogen storage diseases.
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ABSTRACT:
SUBMITTER: Heiner-Fokkema MR
PROVIDER: S-EPMC7605430 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
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The multiple faces of urinary glucose tetrasaccharide as biomarker for patients with hepatic glycogen storage diseases.
Heiner-Fokkema M Rebecca MR van der Krogt Jennifer J de Boer Foekje F Fokkert-Wilts Marieke J MJ Maatman Ronald G H J RGHJ Hoogeveen Irene J IJ Derks Terry G J TGJ
Genetics in medicine : official journal of the American College of Medical Genetics 20200713 11
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Project description:INTRODUCTION:The gut microbiome has been related to several features present in Glycogen Storage Diseases (GSD) patients including obesity, inflammatory bowel disease (IBD) and liver disease. OBJECTIVES:The primary objective of this study was to investigate associations between GSD and the gut microbiota. METHODS:Twenty-four GSD patients on treatment with uncooked cornstarch (UCCS), and 16 healthy controls had their faecal microbiota evaluated through 16S rRNA gene sequencing. Patients and controls were ≥3 years of age and not on antibiotics. Faecal pH, calprotectin, mean daily nutrient intake and current medications were recorded and correlated with gut microbiome. RESULTS:Patients' group presented higher intake of UCCS, higher prevalence of IBD (n = 04/24) and obesity/overweight (n = 18/24) compared to controls (n = 0 and 06/16, respectively). Both groups differed regarding diet (in patients, the calories' source was mainly the UCSS, and the intake of fat, calcium, sodium, and vitamins was lower than in controls), use of angiotensin-converting enzyme inhibitors (patients = 11, controls = 0; p-value = 0.001) multivitamins (patients = 22, controls = 01; p-value = 0.001), and mean faecal pH (patients = 6.23; controls = 7.41; p = 0.001). The GSD microbiome was characterized by low diversity and distinct microbial structure. The operational taxonomic unit (OTU) abundance was significantly influenced by faecal pH (r = 0.77; p = 6.8e-09), total carbohydrate (r = -0.6; p = 4.8e-05) and sugar (r = 0.057; p = 0.00013) intakes. CONCLUSIONS:GSD patients presented intestinal dysbiosis, showing low faecal microbial diversity in comparison with healthy controls. Those findings might be due to the disease per se, and/or to the different diets, use of UCSS and of medicines, and obesity rate found in patients. Although the main driver of these differences is unknown, this study might help to understand how the nutritional management affects GSD patients.
| S-EPMC6445422 | biostudies-literature
Project description:The association between bone mineral density (BMD) and hepatic glycogen storage diseases (GSDs) is still unclear. To evaluate the BMD of patients with GSD I, IIIa and IXα, a cross-sectional study was performed, including 23 patients (GSD Ia = 13, Ib = 5, IIIa = 2 and IXα = 3; median age = 11.9 years; IQ = 10.9-20.1) who underwent a dual-energy X-ray absorptiometry (DXA). Osteocalcin (OC, n = 18), procollagen type 1 N-terminal propeptide (P1NP, n = 19), collagen type 1 C-terminal telopeptide (CTX, n = 18) and 25-OH Vitamin D (n = 23) were also measured. The participants completed a 3-day food diary (n = 20). Low BMD was defined as a Z-score ≤ -2.0. All participants were receiving uncooked cornstarch (median dosage = 6.3 g/kg/day) at inclusion, and 11 (47.8%) presented good metabolic control. Three (13%) patients (GSD Ia = 1, with poor metabolic control; IIIa = 2, both with high CPK levels) had a BMD ≤ -2.0. CTX, OC and P1NP correlated negatively with body weight and age. 25-OH Vitamin D concentration was decreased in seven (30.4%) patients. Our data suggest that patients with hepatic GSDs may have low BMD, especially in the presence of muscular involvement and poor metabolic control. Systematic nutritional monitoring of these patients is essential.
| S-EPMC8469033 | biostudies-literature
Project description:AimThe urinary glucose tetrasaccharide, Glcα1-6Glcα1-4Glcα1-4Glc (Glc4), is a glycogen limit dextrin that is elevated in patients with glycogen storage disease (GSD) type III. We evaluated the potential of uncooked cornstarch therapy to interfere with Glc4 monitoring, by measuring the diurnal variability of Glc4 excretion in patients with GSD III.MethodsVoids were collected at home over 24 hours, stored at 4°C and frozen within 48 hours. Glc4 was analyzed using liquid chromatography-tandem mass spectrometry and normalized to creatinine.ResultsSubjects with GSD III (median age: 13.5 years, range: 3.7-62; n = 18) completed one or more 24-hour urine collection, and 28/36 collections were accepted for analysis. Glc4 was elevated in 16/18 subjects (median: 13 mmol/mol creatinine, range: 2-75, reference range: <3). In collections with elevated Glc4 (23/28), two-thirds (15/23) had low diurnal variability in Glc4 excretion (coefficient of variation [CV%] <25). The diurnal variability was significantly correlated with the Glc4 concentration (Pearson R = .644, P < .05), but not with the dose of uncooked cornstarch. High intraday variability (>25%) was not consistently observed in repeat collections by the same subject.ConclusionsThe extent and variability of Glc4 excretion relative to creatinine was not correlated with cornstarch dose. A majority of collections showed low variability over 24 hours. These findings support the use of single time-point collections to evaluate Glc4 in patients with GSD III treated with cornstarch. However, repeat sampling over short time-periods will provide the most accurate assessment of Glc4 excretion, as intraday variability may be increased in patients with high Glc4 excretion.
| S-EPMC7932871 | biostudies-literature
Project description:Background: Hepatic glycogen storage diseases (GSDs) are inborn errors of metabolism affecting the synthesis or breakdown of glycogen in the liver. This study, for the first time, systematically assessed vitamin B12 status in a large cohort of hepatic GSD patients. Methods: Plasma vitamin B12, total plasma homocysteine (tHcy) and methylmalonic acid concentrations were measured in 44 patients with hepatic GSDs and compared to 42 healthy age- and gender-matched controls. Correlations of vitamin B12 status with different disease markers of GSDs (including liver transaminase activities and triglycerides) as well as the vitamin B12 intake were studied. Results: GSD patients had significantly higher plasma vitamin B12 concentrations than healthy controls (p = 0.0002). Plasma vitamin B12 concentration remained elevated in GSD patients irrespective of vitamin B12 intake. Plasma vitamin B12 concentrations correlated negatively with triglyceride levels, whereas no correlations were detected with liver transaminase activities (GOT and GPT) in GSD patients. Merging biomarker data of healthy controls and GSD patients showed a positive correlation between vitamin B12 status and liver function, which suggests complex biomarker associations. A combined analysis of biomarkers permitted a reliable clustering of healthy controls versus GSD patients. Conclusions: Elevated plasma concentration of vitamin B12 (irrespective of B12 intake) is a common finding in patients with hepatic GSD. The negative correlation of plasma vitamin B12 with triglyceride levels suggests an influence of metabolic control on the vitamin B12 status of GSD patients. Elevated vitamin B12 was not correlated with GOT and GPT in our cohort of GSD patients. Merging of data from healthy controls and GSD patients yielded positive correlations between these biomarkers. This apparent dichotomy highlights the intrinsic complexity of biomarker associations and argues against generalizations of liver disease and elevated vitamin B12 in blood. Further studies are needed to determine whether the identified associations are causal or coincidental, and the possible impact of chronically elevated vitamin B12 on GSD.
| S-EPMC7463656 | biostudies-literature
Project description:BackgroundGlycogen storage disease (GSD) is a relatively rare inborn metabolic disorder, our study aims to investigate the genotypic and clinical feature of hepatic GSDs in China.MethodsThe clinical and genotypic data of 49 patients with hepatic GSDs were collected retrospectively and analyzed.ResultsAfter gene sequencing, 49 patients were diagnosed as GSDs, including GSD Ia (24 cases), GSD IIIa (11 cases), GSD IXa (8 cases), GSD VI (3 cases) and GSD Ib (3 cases). About 45 gene variants of G6PC, AGL, PHKA2, PYGL, and SLC37A4 were detected; among which, 22 variants were unreported previously. c.648G>T (p. Leu216Leu) of G6PC exon 5 is the most common variant for GSD Ia patients (20/24,83.33%）, splice variant c.1735+1G>T of AGL exon 13 is relatively common among GSD IIIa, while novel variant accounts for the majority of GSD IXa and GSD VI patients. As for clinical features, there was no significant difference in the onset age among group GSD Ia, GSD IIIa, and GSD IXa, but the age at diagnosis and average disease duration from diagnosis of GSD Ia were significantly higher than GSD IIIa and GSD IXa. Body weight of GSD patients was basically normal, but growth retardation was relatively common among them, especially for GSD Ia patients; and renomegaly was only found in GSD Ia. Besides, serum cholesterol, triglyceride, lactic acid, and uric acid in GSD Ia were significantly higher than those with GSD IIIa and IXa (p < 0.05); but ALT, AST, CK, and LDH of GSD III and GSD IXa were significantly higher when compared to GSD Ia (p < 0.05).ConclusionsAll hepatic GSDs patients share similarity in clinical and biochemical spectrum, but delayed diagnosis and biochemical metabolic abnormalities were common in GSD Ia. For family with GSD proband, pedigree analysis and genetic testing is strongly recommended.
| S-EPMC7549605 | biostudies-literature
Project description:Hepatic glycogen storage diseases (GSDs) are inborn errors of metabolism whose dietary treatment involves uncooked cornstarch administration and restriction of simple carbohydrate intake. The prevalence of feeding difficulties (FDs) and orofacial myofunctional disorders (OMDs) in these patients is unknown.ObjectiveTo ascertain the prevalence of FDs and OMDs in GSD.MethodsThis was a cross-sectional, prospective study of 36 patients (19 males; median age, 12.0 years; range, 8.0-18.7 years) with confirmed diagnoses of GSD (type Ia = 22; Ib = 8; III = 2; IXa = 3; IXc = 1). All patients were being treated by medical geneticists and dietitians. Evaluation included a questionnaire for evaluation of feeding behavior, the orofacial myofunctional evaluation (AMIOFE), olfactory and taste performance (Sniffin' Sticks and Taste Strips tests), and facial anthropometry.ResultsNine (25%) patients had decreased olfactory perception, and four (11%) had decreased taste perception for all flavours. Eight patients (22.2%) had decreased perception for sour taste. Twenty-six patients (72.2%) had FD, and 18 (50%) had OMD. OMD was significantly associated with FD, tube feeding, selective intake, preference for fluid and semisolid foods, and mealtime stress (p < 0.05). Thirteen patients (36.1%) exhibited mouth or oronasal breathing, which was significantly associated with selective intake (p = 0.011) and not eating together with the rest of the family (p = 0.041). Lower swallowing and chewing scores were associated with FD and with specific issues related to eating behavior (p < 0.05).ConclusionThere is a high prevalence of FDs and OMDs in patients with GSD. Eating behavior, decreased taste and smell perception, and orofacial myofunctional issues are associated with GSD.
| S-EPMC6336547 | biostudies-literature
Project description:Glycogen storage diseases (GSDs), also referred to as glycogenoses, are inherited metabolic disorders of glycogen metabolism caused by deficiency of enzymes or transporters involved in the synthesis or degradation of glycogen leading to aberrant storage and/or utilization. The overall estimated GSD incidence is 1 case per 20000-43000 live births. There are over 20 types of GSD including the subtypes. This heterogeneous group of rare diseases represents inborn errors of carbohydrate metabolism and are classified based on the deficient enzyme and affected tissues. GSDs primarily affect liver or muscle or both as glycogen is particularly abundant in these tissues. However, besides liver and skeletal muscle, depending on the affected enzyme and its expression in various tissues, multiorgan involvement including heart, kidney and/or brain may be seen. Although GSDs share similar clinical features to some extent, there is a wide spectrum of clinical phenotypes. Currently, the goal of treatment is to maintain glucose homeostasis by dietary management and the use of uncooked cornstarch. In addition to nutritional interventions, pharmacological treatment, physical and supportive therapies, enzyme replacement therapy (ERT) and organ transplantation are other treatment approaches for both disease manifestations and long-term complications. The lack of a specific therapy for GSDs has prompted efforts to develop new treatment strategies like gene therapy. Since early diagnosis and aggressive treatment are related to better prognosis, physicians should be aware of these conditions and include GSDs in the differential diagnosis of patients with relevant manifestations including fasting hypoglycemia, hepatomegaly, hypertransaminasemia, hyperlipidemia, exercise intolerance, muscle cramps/pain, rhabdomyolysis, and muscle weakness. Here, we aim to provide a comprehensive review of GSDs. This review provides general characteristics of all types of GSDs with a focus on those with liver involvement.
| S-EPMC10354582 | biostudies-literature
Project description:BackgroundHepatic glycogen storage diseases (GSDs) are characterised by enzyme defects affecting liver glycogen metabolism, where carbohydrate supplementation to prevent overnight hypoglycaemia is common. Concerns around sleep quality in hepatic GSDs relate to emerging evidence that overnight dysglycaemia impacts sleep quality.MethodsThis prospective observational study reported sleep quality and duration in children with hepatic GSDs over 7 days utilising: actigraphy (Actiwatch 2 by Phillips Respironics), sleep diaries, proxy reported age-appropriate sleep and quality-of-life (QoL) questionnaires, in the context of nocturnal glycaemic profiles continuous glucose monitor (CGM, Dexcom G6) and nocturnal dietary management strategies. Significant hypo- and hyperglycaemia were defined as ≥1% of sleep diary documented nocturnal period, recording <3.5 and >10.0 mmol/L, respectively.ResultsSeven children with hepatic GSD (aged 1-17 years) participated. Objective sleep quality was poor, with actigraphy demonstrating that no child achieved the minimum sleep duration recommended for age. Subjective sleep quality was also poor, with 4/5 documenting significant daytime sleepiness and 6/6 reporting poor sleep hygiene. Children prescribed overnight bolus feeds (OBF) (n = 2) recorded shorter sleep duration compared to other nocturnal management strategies. Parent-reported QoL suggested poor disease-related QoL outcomes for this cohort.ConclusionObjective and subjective sleep disturbances and reduced QoL are common within our sample of children with hepatic GSD. From our observations these outcomes may be linked to nutritional overnight interventions, especially OBFs, rather than overnight glucose levels. Consideration of the impacts of overnight feeding strategies on sleep quality and QoL in children with hepatic GSD should inform future management strategies.
| S-EPMC11667772 | biostudies-literature
Project description:BackgroundGlycogen storage disease (GSD) type 0, VI and IX are inborn errors of metabolism involving hepatic glycogen synthesis and degradation. We performed a characterization of a large Italian cohort of 30 patients with GSD type 0a, VI, IXa, IXb and IXc. A retrospective evaluation of genetical, auxological and endocrinological data, biochemical tests, and nutritional intakes was assessed. Eventual findings of overweight/obesity and insulin-resistance were correlated with diet composition.ResultsSix GSD-0a, 1 GSD-VI, and 23 GSD-IX patients were enrolled, with an age of presentation from 0 to 72 months (median 14 months). Diagnosis was made at a median age of 30 months, with a median diagnostic delay of 11 months and a median follow-up of 66 months. From first to last visit, patients gained a median height of 0.6 SDS (from - 1.1 to 2.1 SDS) and a median weight of 0.5 SDS (from - 2.5 to 3.3 SDS); mean and minimal glucose values significant improved (p < 0.05). With respect to dietary intakes, protein intake (g/kg) and protein intake (g/kg)/RDA ratio directly correlated with the glucose/insulin ratio (p < 0.05) and inversely correlated with HOMA-IR (Homeostasis model assessment of insulin resistance, p < 0.05), BMI SDS (p < 0.05) and %ibw (ideal body weight percentage, p < 0.01).ConclusionA prompt establishment of specific nutritional therapy allowed to preserve growth, improve glycemic control and prevent liver complication, during childhood. Remarkably, the administration of a high protein diet appeared to have a protective effect against overweight/obesity and insulin-resistance.
| S-EPMC9295101 | biostudies-literature
Project description:Hepatic glycogen storage diseases (GSD) underscore the intimate relationship between carbohydrate and lipid metabolism. The hyperlipidemias in hepatic GSD reflect perturbed intracellular metabolism, providing biomarkers in blood to monitor dietary management. In different types of GSD, hyperlipidemias are of a different origin. Hypertriglyceridemia is most prominent in GSD type Ia and associated with long-term outcome morbidity, like pancreatitis and hepatic adenomas. In the ketotic subtypes of GSD, hypertriglyceridemia reflects the age-dependent fasting intolerance, secondary lipolysis and increased mitochondrial fatty acid oxidation. The role of high protein diets is established for ketotic types of GSD, but non-traditional dietary interventions (like medium-chain triglycerides and the ketogenic diet) in hepatic GSD are still controversial and necessitate further studies. Patients with these rare inherited disorders of carbohydrate metabolism meet several criteria of the metabolic syndrome, therefore close monitoring for cardiovascular diseases in ageing GSD patients may be justified.
| S-EPMC4432100 | biostudies-literature