Disorders of Carbohydrate Metabolism

 

Disorders of carbohydrate metabolism is occurred in many different forms. Most of them are acquired. Example, diabetic ketoacidosis, hyperosmolar coma and hypoglycemia. Others are rare inborn errors of metabolism. Mostly they are inherited defects and are mainly autosomal recessive traits. Example, glycogen storage disease. As such inherited diseases are first identified in a family. Some other common examples are galactosaemia, fructose intolerance, lactose intolerance.

Inherited disorders of carbohydrates metabolism occur mainly due to inherited enzyme deficiency. May be due to mutation that change enzyme function or abolish enzyme activity. Most are recessive. Hence only one functional gene is sufficient to produce the enzyme.

In glycogen storage disorders, group of inherited disorders characterized by, deposition of an abnormal type/ quantity of glycogen in tissues, failure to mobilize glycogen. Due to defects in enzyme for glycogen degradation/ rarely glycogen synthesis. Result either, in glycogen that has an abnormal structure or in the accumulation of excessive amounts of normal glycogen. A particular enzyme may be defective in a single tissue, in liver- result in hypoglycemia. In muscle – muscle weakness. Can be more generalized, affecting a variety of tissues. The severity of the glycogen storage disorders ranges from fetal in early childhood to mild disorders that are not life threatening. Glycogen storage disease is an inherited autosomal recessive (inborn errors) disease. Males and females are equally affected. Results from mutations in genes that code for proteins involved in various steps of glycogen synthesis, degradation or regulation hence named glycogen storage disease. Between meals, most tissues depend on glucose generated predominantly in the liver and kidney. Glucose homeostasis is dependent upon the activity of the glucose -6- phosphatases complex.

i.                 A glucose-6-phosphate transporter

ii.               A Glc-6-Pase catalytic unit.

 

 

Glycogenolysis

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Glucose-6-phosphate

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Dephosphorylated by glucose-6- pase

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Free glucose

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Used by the body

 

 

 

                                    Glycogen and glucose – 6- phosphate accumulate/ no alternative route

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                                    Glycogen synthesis continues in the post absorptive stage

                                                      

                                    Characteristics

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                                    Hepatomegaly

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                                    Diagnose liver biopsy

 

 

Sheets of swollen hepatocytes- typically arranged in a mosaic pattern with centrally placed nuclei.

Glycogen storage disease either be, catalytic subunit (type Ia; von Gierke disease), glucose-6-phoaphate transporter (type Ib), Ic and Id are allelic defects in the translocase associated with glucose-6-phosphatase. These are very rare.

 

Type Ia – Von Gierke disease, due to glucose 6- phosphayase deficiency.

Type Ib – due to glucose 6-phosphate translocase deficiency.

It affects the liver and kidney. Fasting hypoglycemia, fatty liver, hepato and venomegaly, progressive and renal disease, growth retardation and delayed puberty, hyperlacticacidemia, hyperlipidemia and hyperuricemia are can be seen. Normal glycogen levels are increased and glycogen is stored. Type Ib is characterized by neutropenia and recurrent infections. Treatment, nocturmal gastric infusions or regular administration of uncooked cornstarch.

 

Glycogen storage disease type ii, Pompe disease.

In this disease, lysosomal degradation of glycogen is decreased. Small amount (1%-3%) of glycogen is degraded by the lysosomal enzyme, alpha (1-4) glucosidase (acid maltase). The purpose of this pathway is unknown. Deficiency of this enzyme causes accumulation of glycogen in vacuoles in the lysosomes, results in serious glycogen storage disease type ii – Pompe disease. This is the only glycogen storage disease that is a lysosomal storage disease.