Most patients with moderate to severe glycogen storage disease experience some g

Question

Most patients with moderate to severe glycogen storage disease experience some growth retardation. What feature of the glycogen storage diseases would account for this? Use details related to biochemistry.

CLINICAL CONNECTION Glycogen Storage Diseases The glycogen storage discases are a set of inherited disorders of like many lysosomal enzymes, apparently plays a role in recy- slycogen metabolism, not all of which result in glycogen accu cling cellular materials. Glycogen accumulates in the lysosomes mulation, as the name might suggest. The symptoms of the eventually killing the cell. sycogen storage diseases vary, depanding on whether the affect- In the past, glycogen storage diseases were diagnosed on the od tissue is liver or muscle or both. In general, the disorders that basis of symptoms, blood tests, and painful biopsies of liver or affecet the liver cause hypoglycemia (too little glucose in the muscle to assess its glycogen content. Current diagnostic methods blood) and an enlarged liver. Glycogen storage diseases that are centered on analyzing the relevant genes for mutations, a non- affect primarily muscle are characterized by muscle weakness invasive approach Treatment of glycogen storage diseases typically and cramps. The incidence of glycogen storage discases is esti- inclades a regimen of frequent, small, carbohydrate-rich meals to mated to be as high as 1 in 20,000 births, although some disor- alleviate hypoglycemia However, because dietary therapy does not ders are nor appareat until adulthood. Twelve types of glycogen completely eliminate the symptoms of some glycogen storage storage diseases have been described, and the defect in each is discases, and because the metabolic aboormalities, such as listed in the table an the next page. The following discussion bypoglycemia and liver damage, can severely impair physical focuses on the most common of these conditions.. growth as well as cognitive development, liver transplant has proved to be an effective treatment. At least one disorder, the type A defect of glucocose-6-phosphatase ( (type I glycogen storage von Gierke's discase) affects both gluconeo- II glycogen storage discase, has been treated with infusions of the glucose-6-phosphatase cata- missing enzyme. The glycogen storage diseases are single-gene defects, which makes them attractive targets for gene therapy (see genesis and glycogenolysis, since cata- lyzes the final step of gluconeogenesis and makes free glucose available from glycogenolysis The enlarged liver and hypogly- cemia can lead to a host of other symptoms, including irritabil- ity, lethargy, and, in severe cases, death. A related defect is the T deficiency of the transport protein that imports glucose-6- phosphate into the endoplasthic reticulum, where the phos-I phatase is located Amylo-1,6-glucosidase (debranching enzyme Amylo-(1,4-1,6)-tranglycosylase Type III glycogen storage disease, or Cori's disease, results from a deficiency of the glycogen debranching enzyme. This condition accounts for about one-quarter of all cases of glycogen y storage disease and usually affects both liver and muscle. The symptoms include muscle weakness and liver enlargement due to v the accumulation of glycogen that cannot be efficiently broken down. The symptoms of type III glycogen storage discase often viil, xxPhosphorylase kinase improve with age and disappear by early adulthood. Muscle glycogen phosphorylase Liver glycogen phosphorylase trarsporter The most common type of glycogen storage disease is type Dx. In this disorder, the kinase that activates glycogen phosphorylase is defective. Symptoms range from severe to mild and may fade with time. The complexity of this disease reflects the fact that the phosphorylase kinase consists of four subunits, with isoforms that are differentially expressed in the liver and other tissues. Genes for the a chain (the kinase eatalytic subunit) are located on the X chromosome, so one form of disease (type VIII glycogen storage disease) is inherited in a sex-linked manner (more males than females are affected). Genes for the B. Y, and 8 subunits of the kinase, which have regulatory functions, are on other chromo- somes, so defects in these genes affect males and females equally Type II glycogen storage disease, the deficiency of a muscle glucosidase, is not common, but it causes death within the first year. The missing enzyme is a lysosomal hydrolase that does not participate in the main pathways of glycogen degradation but

Explanation / Answer

Glycogen-storage diseases is a typpe of autosomal recessive disorders characterized by developmental delays, kidney disease, delayed puberty and polycystic ovaries due to an inability to convert glycogen into glucose. It was first described in 1963 as glycogen synthethase deficiency in the liver, due to a marked decrease in liver glycogen content, in fact, GSD-0 is not a true GSD. The gene is located on chromosome 12 p 12.1. There are many phenotypical variations. The symptoms are due to hypoglycemia and include lethargy, pallor, nausea, vomiting, and sometimes seizures in the morning before breakfast. There will be a developmental delay that develops in some children, most children are cognitively and developmentally normal. Some patients may survive without symptoms or with very mild symptoms.

Related Questions

Navigate

• Browse (All)
• Browse M
• Subjects

---

---

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.