- Resting energy expenditure and substrate oxidation in malnourished patients with type 1 glycogenosis. [Journal Article]
- JCJ Clin Endocrinol Metab 2019 Jul 19
- CONCLUSIONS: According to data obtained in this small sample of patients with GSD1, an elevated REE seems to be a common characteristic that may contribute to malnutrition. A low basal protein oxidation rate and elevated blood lactic acid concentrations appear to be associated with malnutrition.
- Modified Atkins ketogenic diet improves heart and skeletal muscle function in glycogen storage disease type III. [Journal Article]
- AMActa Myol 2019; 38(1):17-20
- Glycogen storage disease type III (GSDIII) management in adult patients includes a high-protein diet with cornstarch supplementation to maintain a normal level of glucose in the blood. This regimen c…
Glycogen storage disease type III (GSDIII) management in adult patients includes a high-protein diet with cornstarch supplementation to maintain a normal level of glucose in the blood. This regimen can prevent hypoglycaemia but does not seem to improve skeletal muscle and heart function. A 34 years-old patient with GSD IIIa with hypertrophic cardiomyopathy was then treated with a modified Atkins ketogenic diet. After 12 months of treatment ejection fraction raised from 30 to 45%, liver enzymes were reduced and CK plasma level dropped from 568 to 327 U/l. Physical activity increased from about 1300 to 2800 steps per day and health-related quality of life assessment ameliorated. An increase in uric acid triglycerides plasma level was observed. This data obtained in an adult patient confirm previous reports evidencing the effectiveness of ketogenic diets in improving cardiac and muscular manifestations in children with GSDIII.
- Identification of patients with Pompé disease using routine pathology results: PATHFINDER (creatine kinase) study. [Journal Article]
- JCJ Clin Pathol 2019 Jul 15
- CONCLUSIONS: Screening pathology databases for elevated CK may identify patients with inherited metabolic errors affecting muscle metabolism. However, the frequency of Pompé's disease identified from laboratory populations was less than that in patients referred for neurological investigation.
- Assessment of the functional impact on the pre-mRNA splicing process of 28 nucleotide variants associated with Pompe disease in GAA exon 2 and their recovery using antisense technology. [Journal Article]
- HMHum Mutat 2019 Jul 13
- Glycogen storage disease II (GSDII), also called Pompe disease, is an autosomal recessive inherited disease caused by a defect in glycogen metabolism due to the deficiency of the enzyme acid alpha-gl…
Glycogen storage disease II (GSDII), also called Pompe disease, is an autosomal recessive inherited disease caused by a defect in glycogen metabolism due to the deficiency of the enzyme acid alpha-glucosidase (GAA) responsible for its degradation. So far, more than 500 sequence variants of the GAA gene have been reported but their possible involvement on the pre-mRNA splicing mechanism has not been extensively studied. In this work, we have investigated, by an in vitro functional assay, all putative splicing variants within GAA exon 2 and flanking introns. Our results show that many variants falling in the canonical splice site or the exon can induce GAA exon 2 skipping. In these cases, therefore, therapeutic strategies aimed at restoring protein folding of partially active mutated GAA proteins might not be sufficient. Regarding this issue, we have tested the effect of antisense oligonucleotides (AMOs) that were previously shown capable of rescuing splicing misregulation caused by the common c.-32-13T>G variant associated with the childhood/adult phenotype of GSDII. Interestingly, our results show that these AMOs are also quite effective in rescuing the splicing impairment of several exonic splicing variants, thus widening the potential use of these effectors for GSDII treatment. This article is protected by copyright. All rights reserved.
- Gene therapy for Pompe disease: the time is now. [Journal Article]
- HGHum Gene Ther 2019 Jul 12
- Pompe disease (PD) is caused by the deficiency of the lysosomal enzyme acid α-glucosidase (GAA), resulting in systemic pathological glycogen accumulation. PD can present with cardiac, skeletal muscle…
Pompe disease (PD) is caused by the deficiency of the lysosomal enzyme acid α-glucosidase (GAA), resulting in systemic pathological glycogen accumulation. PD can present with cardiac, skeletal muscle, and central nervous system (CNS) manifestations, as a continuum of phenotypes among two main forms: classical infantile-onset PD (IOPD) and late-onset PD (LOPD). IOPD is caused by severe GAA deficiency and presents at birth with cardiac hypertrophy, muscle hypotonia and severe respiratory impairment, leading to premature death, if not treated. LOPD is characterized by levels of residual GAA activity up to ~20% of normal and presents both in children and adults with a varied severity of muscle weakness, motor and respiratory deficit. Enzyme replacement therapy (ERT), based on repeated intravenous infusions of recombinant human GAA (rhGAA), represents the only available treatment for PD. Upon more than 10 years from its launch, it is becoming evident that ERT can extend the lifespan of IOPD and stabilize disease progression in LOPD, however it does not represent a cure for PD. The limited uptake of the enzyme in key affected tissues and the high immunogenicity of rhGAA are some of the hurdles that limit ERT efficacy. GAA gene transfer with adeno-associated virus (AAV) vectors has been shown to reduce glycogen storage and improve the PD phenotype in pre-clinical studies following different approaches. Here, we will present an overview of the different gene therapy approaches for PD, focusing on in vivo gene transfer with AAV vectors and discussing the potential opportunities and challenges in developing safe and effective gene therapies for the disease. Based on emerging safety and efficacy data from clinical trials for other protein deficiencies, in vivo gene therapy with AAV vectors appears to have the potential to provide a therapeutically relevant, stable source of GAA enzyme, which could be highly beneficial in PD.
- Late-onset Pompe disease manifests in the brain. [Journal Article]
- MGMol Genet Metab Rep 2019; 20:100488
- PRE AND POST-OPERATIVE OTORHINOLARYNGOLOGY SURGERY CARE IN PATIENTS WITH GLYCOGEN STORAGE DISEASE TYPE 1. [Journal Article]
- RPRev Paul Pediatr 2019 Jul 04
- CONCLUSIONS: Patients with glycogen storage disease type 1b present recurrent infections, including the otorhinolaryngology affections. When there is an indication for surgical treatment, the caloric intake should be carefully followed in order to prevent hypoglycemia. The way to ensure this is to perform the pre and postoperative period in the hospital ward. In the postoperative period, it is important to make a slow transition between the intravenous and oral routes and not suspend the infusion of glucose during the surgical procedure. The cases illustrate the need for the interaction of the otorhinolaryngologic surgeon with the anesthesiologist, the pediatrician and the gastro-pediatrician in the management of these patients, avoiding hypoglycemic episodes.
- Rehabilitation management of Pompe disease, from childhood trough adulthood: A systematic review of the literature. [Journal Article]
- NINeurol Int 2019 Jun 18; 11(2):7983
- Pompe disease (PD) is a rare neuromuscular disorder caused by a deficiency of the enzyme acid alpha-glucosidase. There are three forms of PD depending on the age at onset and clinical severity. PD ca…
Pompe disease (PD) is a rare neuromuscular disorder caused by a deficiency of the enzyme acid alpha-glucosidase. There are three forms of PD depending on the age at onset and clinical severity. PD causes involvement of different organ systems, such as the heart, musculoskeletal system, and respiratory system. As of today, enzyme replacement therapy represents the main therapeutic tool for PD. Rehabilitation is an integral part of a multidisciplinary approach to this pathology. The goal of the present review is to find scientific evidence for the rehabilitative approach to PD, with respect to both the infantile- and adult-onset forms. A systematic literature review was made using the following databases: Pubmed, Pedro, Cochrane Library, EDS Base Index, Trip, and Cinhal. Randomized controlled trials or cohort studies with a sample population of at least six subjects were retrieved. The PICO method was used to formulate the clinical query. The search resulted in 1665 articles. Of these, four cohort studies were subjected to the final phase of the review. Three studies regarded inspiratory muscle training with a threshold, while the fourth study analyzed the effectiveness of therapeutic, aerobic, and reinforcement exercises. Inspiratory muscle training with a threshold increases the pressures generated during inhalation. Aerobic exercise is capable of increasing patients' muscular endurance and performance. To date, however, rehabilitative treatment for patients with PD has no validation in evidencebased medicine. Further studies, possibly with a larger sample size and higher quality are necessary to confirm the effectiveness of rehabilitation in patients with PD.
- Acute psychosis in glycogen storage disease: a rare but severe complication. [Journal Article]
- BCBMJ Case Rep 2019 Jul 04; 12(7)
- Glycogen storage disease type 1 (GSD-1) is a group of inherited metabolic disorders characterised by the inability to use intracellular glucose stores. It is associated with a high risk of hypoglycae…
Glycogen storage disease type 1 (GSD-1) is a group of inherited metabolic disorders characterised by the inability to use intracellular glucose stores. It is associated with a high risk of hypoglycaemia, as well as long-term complications including growth retardation, hepatocellular adenomas, renal disease, hypertriglyceridaemia and hyperuricaemia. Treatment involves slow absorption carbohydrates, for example, cornstarch. We present a case of acute psychosis in a patient with GSD-1a. This was initially attributed to his opiate use. Later in his management an MRI scan of his head was performed which revealed regions of brain atrophy following significant hypoglycaemic insult, thus identifying an organic cause of his psychosis. This case presents a rare complication of glycogen storage disease: organic psychosis attributable to cortical atrophy from profound hypoglycaemic insult. It emphasises the importance of investigating organic causes of psychiatric symptoms.
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- Liver fibrosis during clinical ascertainment of glycogen storage disease type III: a need for improved and systematic monitoring. [Journal Article]
- GMGenet Med 2019 Jul 02
- CONCLUSIONS: Liver fibrosis can occur at an early age, and may explain the decrease in aminotransferases and Glc4 with age. Our data outlines the need for systematic follow-up and specific biochemical and radiological tools to monitor the silent course of the liver disease process.