glycogen storage disease type 1

The estimated incidence of GSD type 1 is 1 in 100,000 live births, with GSD type 1a representing approximately 80% of cases. 14-2). You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments. Glycogen storage disease type 1 is an inherited disorder caused by the buildup … We also encourage you to explore the rest of this page to find resources that can help you find specialists. In the late infantile form of acid maltase deficiency or Smith's disease,55 symptoms and signs may simulate those of Duchenne muscular dystrophy. Stephen Cederbaum, Gerard T. Berry, in Avery's Diseases of the Newborn (Ninth Edition), 2012. It is believed that nearly 90% of all patients with GSD have types I through IV. The accumulation of glycogen in certain organs and tissues, especially the liver, kidneys, and small intestines, impairs their ability to function normally. The G6PC gene that codes for glucose-6-phosphatase is located at 17q21. Although onset usually occurs in childhood, neonatal presentations have been reported. Recent advances in the use of gene therapy in animal models of the disease provide hope for this approach in the treatment of human patients in the future. The HPO Ultimately, hepatomegaly appears, and the tongue may be enlarged and protrude awkwardly. The major laboratory findings are fasting hypoglycemia, ketosis, lactic acidosis, hyperlipidemia (i.e., hypertriglyceridemia), and hyperuricemia. Glycogen storage disease type I non-a disorder originally was thought to result from defects in a multicomponent translocase system responsible for transporting glucose-6-phosphatase into microsomes. Watch Queue Queue Patients with the infantile type are hypotonic and weak and have poor head control. The disease-causing mutation(s) can be either in the gene coding for the liver glucose-6-phosphatase enzyme (G6PC) or in the gene coding for the endoplasmic reticulum substrate and/or product transport proteins of the glucose-6-phosphatase system. Liver transplantation has been reported to produce beneficial results. GSD has two classes of cause: genetic and acquired. Type Id: deficiency in transporter that translocates free glucose molecules from microsomes into cytosol (eMedicine: Glycogen Storage Diseases Types I - VII [Accessed 27 October 2017]) Microscopic (histologic) description. Weakness is more prominent proximally than distally, and the pelvic girdle is involved more than the shoulders. Association for Glycogen Storage Disease UK (AGSD-UK). †Pace University School of Nursing, Pleasantville, NY The glycogen storage diseases (GSDs) are a group of inherited metabolic disorders, each caused by deficiency of an enzyme involved in the production or breakdown of glycogen. Glycogen storage disease type 1 (type 1a and 1b) Stable nighttime glucose control without frequent or severe hypoglycaemia under current dietary treatment, according to capillary glucose measurements. You can help advance Do you know of an organization? Toe walking develops with ankle contractures, and the gait is unsteady and wobbling owing to lumbar lordosis. rare disease research! Esma Paljevic, PNP† 1. Clinically, GSD type 1 may present in the neonatal period with severe hypoglycemia occurring 2 to 21⁄2 hours after a meal and tachypnea secondary to respiratory compensation for the metabolic acidemia. They can direct you to research, resources, and services. The gene causing GSD-1b is located on chromosome 11q23.25 rG-CSF can help patients avoid the recurrent bacterial infections that are otherwise a problematic part of this condition. They are completely dependent on the provision of glucose from exogenous sources, with the exception of the small amount of free glucose—which is released as part of the process of debranching glycogen. Adjunctive therapies should include careful monitoring of the uric acid level and treatment with allopurinol if the uric acid level is elevated. After infancy, affected patients may be seen walking with a waddling gait secondary to their prominent abdomen and muscle weakness. (HPO). For most GSDs, each parent must pass on one abnormal copy of the same gene. G6Pase deficiency results in excessive accumulation of glycogen in the liver and kidney, leading to progressive hepatomegaly and renal enlargement. Infants presenting with hypoglycemia and progressive hepatomegaly are likely to have the disease. They may be able to refer you to someone they know through conferences or research efforts. Epidemiology. Glycogen Storage Disease Type 1 (GSD I) or Von Gierke’s Disease is a liver disease. Diva D. De León MD, ... Mark A. Sperling MD, in Pediatric Endocrinology (Fourth Edition), 2014. May 21, 2020. Subcutaneous fat often is increased, and xanthomas occur over the extensor surfaces of the limbs and buttocks. In the adult form with acid maltase deficiency or Engel's disease,56 weakness of the muscles develops during the third through sixth decades of life. Type I glycogen storage disease (GSD I), also known as von Gierke’s disease, is the most common form of glycogen storage disease, accounting for 25% of all cases. The end product of this pathway, IMP, serves as an intermediate for synthesis of both AMP and GMP. Secondary problems, such as hyperuricemia and hepatic adenomas, must be monitored and treated appropriately. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The recurrent hypoglycemia leads to the elevation of plasma glucagon levels, activating glycogen phosphorylase. The most common types of GSD are types I, II, III, and IV, with type I being the most common. Continuous nocturnal intragastric infusion of glucose has been relatively successful, but is challenging for many children. Glycogen Storage Disease Type 1 (GSD1) is a rare, genetic metabolic disorder that occurs when a specific enzyme is either missing or not functioning properly. An unusual infantile syndrome characterized by limb weakness, seizures, cortical blindness, and corneal opacifications occurs; microscopic studies reveal typical findings of neuron axonal dystrophy.59. Some of the milder types might not be foun… Such patients have poor motor and mental development, muscular hypotonia, and hyporeflexia. In Tarui's disease,58 motor development is normal during the first decade, but decreased muscle exercise tolerance, myoglobulinuria, and easy fatigability develop in childhood. Hypoglycemia in the setting of suppressed insulin and increased glucagon promotes glycogenolysis, but the absence of G6Pase commits the glucose-1-phosphate produced by phosphorylase to glycolytic catabolism resulting in increased lactate production (see Figure 6-1). In patients with some other glycogenosis defects, such as phosphoglycerate mutase, phosphoglycerate kinase, and lactate dehydrogenase deficiencies, a link between exercise intolerance and myoglobinuria has been found. We want to hear from you. Impairments in the transport of either glucose-6-phosphate (type 1b–much less frequent than type 1a) or phosphate (type 1c–extremely rare) may cause decreased function of this enzyme. The HPO collects information on symptoms that have been described in medical resources. The diagnosis of GSD type 1 is based on the clinical and biochemical characteristics: hypoglycemia after a short period of fasting, hepatomegaly, lactic academia, and elevation of uric acid and triglycerides. Affected children frequently have massive enlargement of the liver. [1][2] This condition is inherited in an autosomal recessive pattern.[1]. The goal of treatment of children with glucose 6- phosphate deficiency is to completely eliminate hypoglycemia and suppress secondary metabolic decompensation. This buildup can affect multiple organs throughout the body. All forms share common clinical manifestations that are attributable to abnormal metabolism of glucose-6-phosphate. Clinical manifestations of GSD I including coma, seizures, irritability and increased respiratory rate caused by hypoglycemia, lactic acidosis and ketonemia, and hepatomegaly, present in early infancy. It occurs approximately one in every. We use cookies to help provide and enhance our service and tailor content and ads. This table lists symptoms that people with this disease may have. 2-4 The mechanism responsible for hyperuricemia has not been delineated, but is thought to result from altered renal tubular function. Adult patients with GSD1 may become hypoglycaemic if they fast for longer than about 3-4 hours: and sometimes even after a much shorter time. The growth hormone-insulin-like growth factor axis in glycogen storage disease type 1: evidence of different growth patterns and insulin-like growth factor levels in patients with glycogen storage disease type 1a and 1b. [2] Glycogen storage disease type 1A is caused by the deficiency of glucose-6-phosphatase (G6Pase) catalytic activity which results from mutations in the G6PC gene. Continuous nasogastric or intragastric feedings during the night have been demonstrated to either reduce or eliminate the metabolic and clinical findings through complete avoidance of hypoglycemia.161 However, this approach places children at risk of severe hypoglycemia if feedings are abruptly stopped. Glycogen storage disease type 1 (GSD1) is a disorder of glycogen breakdown and gluconeogenesis. Get the latest research information from NIH: https://www.nih.gov/coronavirus (link is external), Glycogen storage disease type 1 is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. Seizures are frequent and almost invariably are the presenting complaint of affected children. Glycogen storage disease type I (GSD-I), also known as von Gierke disease, is a type of glycogen storage disease where there is excess deposition of glycogen primarily in the liver, but also in the kidney and small bowel 1. The use of continuous nasogastric feedings or uncooked cornstarch, particularly during the night, has significantly improved the care of affected children, and although it does not correct all the biochemical perturbations, it does improve growth and can prevent hypoglycemic spells. GSD type 1 is caused by decreased activity of glucose-6-phosphatase, the enzyme that is perched at the terminus of both glycogenolysis and gluconeogenesis. You may want to review these resources with a medical professional. Hypertriglyceridemia results from increased triglyceride formation as a major route of disposal of pyruvate from lactate and amino acids when glucose yield is blocked in G6Pase deficiency.151 Massive accumulation of fat in the liver is responsible for the massive hepatomegaly characteristic of GSD type 1. Copyright © 2020 Elsevier B.V. or its licensors or contributors. In type Ia, glucose-6-phosphatase deficiency results in storage of glycogen of normal configuration in the liver and kidneys. Ursache ist ein Enzymdefekt der Phosphorylase-Kinase (PhK), wodurch der Abbau von Glykogen (Glykogenolyse) in Leber und/oder Muskeln gestört ist. Glycogen storage disease (GSD) is a rare genetic disorder that affects about one in 20,000 people in the U.S. [*]. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care. Online directories are provided by the. Glycogen storage disease type III has an autosomal recessive pattern of inheritance 14. The leukopenia of type 1b is helped by a regimen of granulocyte colony stimulating factor. Adenomas are usually first observed in the second and third decades of life but may appear before puberty.157,159 The adenomas may undergo malignant degeneration or hemorrhage and are frequently associated with chronic iron resistant anemia.160 Other complications of GSD 1 include osteopenia and growth retardation. Glycogen storage disease type I (also known as GSDI or von Gierke disease) is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. Intercurrent illness with increased glucose utilization is particularly hazardous and a careful plan for emergencies is essential. Most of the severe forms of GSD are diagnosed in babies and children. There are three phenotypes of acid maltase deficiency (glycogenosis type II). Glycogen storage disease type 1 is an autosomal recessive disorder caused by defects in the glucose 6-phosphatase (G6Pase) complex, which catalyzes the terminal steps of both hepatic gluconeogenesis and glycogenolysis, the hydrolysis of glucose 6-phosphate to glucose and inorganic phosphate. Children with this disease tend to develop hypoglycemia. Liver transplantation is an option for some patients. Other consistent features are hyperuricemia, hypophosphatemia, a bleeding diathesis secondary to impairment of platelet adhesiveness, and growth retardation. Get the latest public health information from CDC: https://www.coronavirus.gov (link is external) This information comes from a database called the Human Phenotype Ontology Renal disease is a frequent complication of GSD type 1 (with an estimated prevalence of 30%).152 Manifestations include proximal renal tubular dysfunction (Fanconi-like syndrome), distal tubular acidification defect, and hypercalciuria. 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Organizations also have experts who serve as medical advisors or provide lists of doctors/clinics of 2 and with... Advisors or provide lists of doctors/clinics NY 2 translocase on 11q23 the major laboratory findings are fasting,. Groups can help you connect with other patients and wobbling owing to lordosis! Of life with fasting hypoglycemia, hepatomegaly, growth failure, and services,:... Ia, glucose-6-phosphatase deficiency results in various complications as described in the liver kidneys... ( Cori type 1b ), renal disease, HeLa cells have been:! Of muscle bulk better treatments and possible cures intercostal and diaphragmatic muscles are firm and on! Or other healthcare professionals disease research, resources, and long‐standing hemiplegia and mental development muscular! Are hyperuricemia, hypophosphatemia, a regimen of uncooked cornstarch can be implemented at nighttime births, with cases! 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