Glycogen Storage Diseases

Glycogen storage diseases are disorders of carbohydrate metabolism and are caused by a deficiency of an enzyme that is involved either the synthesis or the degradation of glycogen. The deficiency can occur in the liver or muscle and causes hypoglycemia or leads to the deposition of abnormal amounts or types of glycogen or its intermediates in the tissues.

The inheritance of glycogen storage diseases (engl.GSDs) are autosomal recessive. An exception is the OTC deficiency (GSD-Type VIII / IX), which is inherited X-linked. The incidence is estimated to be 1 of 25,000 live births. s. Table glycogen storage diseases and disorders of gluconeogenesis for a more complete overview.

Glycogen storage diseases are disorders of carbohydrate metabolism and are caused by a deficiency of an enzyme that is involved either the synthesis or the degradation of glycogen. The deficiency can occur in the liver or muscle and causes hypoglycemia or leads to the deposition of abnormal amounts or types of glycogen or its intermediates in the tissues. The inheritance of glycogen storage diseases (engl.GSDs) are autosomal recessive. An exception is the OTC deficiency (GSD-Type VIII / IX), which is inherited X-linked. The incidence is estimated to be 1 of 25,000 live births. s. Table glycogen storage diseases and disorders of gluconeogenesis for a more complete overview. The age of onset, the clinical manifestations and severity of the disease may vary depending on the type. The symptoms and signs are mostly hypoglycaemia and myopathy. A tentative diagnosis of glycogen storage disease is provided by history and physical examination and retrieval of glycogen or its intermediate metabolite in the tissue using MRI or biopsy. The diagnosis is due to a significant decrease in enzyme activity in the liver (type I, III, VI and VIII / IX), in the muscles (type IIb, III, VII and VIII / IX), in the skin fibroblasts (type IIa and IV) or red blood cells (type VII) or diagnosed with type forearm / ischemia (type V and VII) because of a missing rise in lactate in the venous blood. (See also check on suspicion of inherited metabolic disorders.) The prognosis and treatment of glycogen storage disease varies with the type of treatment typically always includes the transfer of cornstarch to keep in stock a sustainable source of glucose in the hepatic forms of GSE, and in the muscular form avoidance of gymnastics. Disorders in glycolysis (rarely) may cause the GSE syndromes similar. The lack of phosphoglycerate kinase, phosphoglycerate and lactate dehydrogenase can mimic myopathies of the GSE-type V and VII; the lack of Glykogentransportprotein (Bickel-Fanconi syndrome), the hepatopathy of the other GSE types (I, III, IV, VI) mimic. Glycogen storage diseases and disorders of gluconeogenesis disease (OMIM number) Defective proteins or enzymes defective gene or genes (chromosomal location) Comments GSD I frequent (From Gierke’s disease) form of GSD I: Ia (> 80%) Start: In the first year of life Clinical features: In the first year of life severe hypoglycemia, lactic acidosis and hepatomegaly, hepatic adenomas later, renomegaly with progressive renal failure and high blood pressure, short stature, hypertriglyceridemia, hyperuricemia, platelet dysfunction with epistaxis and anemia In type Ib Weni ger hard, but including neutropenia, neutrophil dysfunction with recurrent infections and inflammatory bowel disease treatment: uncooked cornstarch 1.5-2.5 g / kg p.o. every 4-6 h or lactose-free infant formula with maltodextrin to maintain normoglycemia; nocturnal feeding (important); Fructose and galactose restriction; When lactic acidosis: bicarbonate 0.25-0.5 mmol / kg four times a day; Allopurinol, to keep the uric acid in <6.4 mg / dl; Liver and kidney transplantation (to be successful) in type Ib patients with neutropenia, G-CSF type Ia (232200) glucose-6-phosphatase G6PC (17q21) * Type Ib (232220) glucose-6-phosphate translocase G6PT1 (11q23 ) * type Ic (232240) Microsomal phosphate or Pyrophosphattransporter G6PT1 (11q23) * type Id Microsomal glucose transporter Wahrsc heinlich as Ic GSD II (Pompe's disease, 232300) Starting in infancy, in childhood or adulthood; remaining enzyme activity in infant and adult forms Clinical features: In the infantile form cardiomyopathy with heart failure, severe hypotension, macroglossia In the juvenile and adult forms of skeletal myopathy with delayed motor development, progressive peripheral airway and muscle weakness In Type IIb, mental retardation treatment: None known for cardiomyopathy, cardiac transplant type IIa Lysosomalsäure ?-glucosidase GAA (17q25) * type IIb (Danon) lysosomal membrane protein-2 LAMP2 (Xq24) * GSD III (Forbes disease, Cori crane kheit, borderline Dextrinose; 232400) Frequency: IIIa, 85%; IIIb, rarely start 15%, IIIc and IIId: in infancy or childhood Clinical Characteristics: Type IIIa, liver and muscle involvement with features of type I and II In Type IIIb only liver involvement with additional hallmark of type Ia For the types IIIc and IIId various features depending on the affected tissue treatment: raw corn starch and continuous feeding, to obtain the Normoglycämie; protein diet to stimulate gluconeogenesis types IIIa and IIIb débrancher enzyme (amyloglucosidase and oligoglucanotransferase) AGL (1p21) * Type IIIc only amyloglucosidase type IIId only Oligoglukanotransferase GSD IV (Andersen disease; 232500) branching enzyme GBE1 (3P12) * Start : in the early K indheit; rare in the neonatal period, in late childhood or adulthood (manifested as nonprogressive variant or a neuromuscular form) Clinical features: hepatomegaly with progressive liver cirrhosis and hypoglycemia, esophageal varices and ascites; splenomegaly; Failure to thrive In neuromuscular forms: hypotension and muscle atrophy Treatment: No known case of cirrhosis, liver transplantation, the treated just the primary disease virtually GSD V (McArdle disease; 232600) muscle phosphorylase PYGM (11q13) * Starting in adolescence or early adulthood clinical features: exercise intolerance due to muscle spasms, rhabdomyolysis treatment: carbohydrate offering before the workout, high protein diet GSD VI (Hers disease; 232700) Leberphosphorylase PYGL (14q21-q22) * frequency: rare start: In early childhood, K linische features: benign course with symptoms diminish with aging, growth disorders, hepatomegaly, hypoglycemia, hyperlipidemia, ketosis treatment: None required GSD VII (Tarui disease; 232800) phosphofructokinase PFKM (12q13.3) * Start: in middle childhood Clinical features: exercise intolerance due to muscle spasms, rhabdomyolysis, hemolysis treatment: Unspecific; Prevention of movement GSD VIII / IX (306000, 172490, 604549, 311870) - Start: heterogeneous Clinical features: heterogeneous; Hepatomegaly, growth retardation, hypotonia, hypercholesterolemia Treatment: unspecific type VIII / Xa: X-linked phosphorylase kinase PHKA2 (Xp22) * Type IXb liver and Muskelphosphorylasekinase PHKB (16q12-Q13) * Type IXc Leberphosphorylasekinase PHKG2 (16p12.1-p11.2) * type IXd Muskelphosphorylasekinase PHKA1 (Xq13) * GSD O (240600) glycogen synthase GYS2 (12P12) * Start: Variable, but often after the end of the night feedings or intercurrent disease Clinical features: hypoglycemia by fasting and ketosis, postprandial lactic acidosis Treatment: Frequent high-protein meals, at bedtime uncooked cornstarch Fanconi Bickel syndrome (227810) glucose transporter GLUT2 2 (3q26) * Starting in childhood Clinical features: failure to thrive, abdominal distention, hepatomegaly, renomegaly, mild hypoglycemia in fasting and hyperlipidemia, glucose intolerance, renal Fanconi syndrome treatment: Di ät similar to diabetes, replacement of renal lost electrolytes, vitamin D, fructose 1,6-diphosphatase deficiency (229700) fructose 1,6-biphosphatase FBP1 (9q22) * Start: in infancy or early childhood Clinical features: Episodic hyperventilation, respiratory arrest , hypoglycemia, lactic acidosis or ketosis; provoked by fasting, febrile infection or by ingestion of fructose, sorbitol or glycerine treatment: avoidance of fasting and fructose, sorbitol and glycerol; Uncooked cornstarch phosphoenolpyruvate deficiency (261680) phosphoenolpyruvate PCK1 (20q13,31) * Starting in childhood Clinical features: failure to thrive, hypotonia, hepatomegaly, lactic acidosis, hypoglycemia treatment: No fasting, raw corn starch * The gene was identified, and the molecular basis has been elucidated , G-CSF = granulocyte-colony stimulating factor; GSD = glycogen storage disease; OMIM = Online Mendelian Inheritance in Man (s. OMIM database).

Health Life Media Team

Leave a Reply