CARBOHYDRATE METABOLISM- INHERITED

DISORDERS

DR. Tagreed Osman

• Carbohydrates are sugars. Some sugars are simple, and others are more complex. Sucrose (table sugar) is made of two simpler sugars called glucose and fructose. Lactose (milk sugar) is made of glucose and galactose. Both sucrose and lactose must be broken down into their component sugars by enzymes before the body can absorb and make use of them.

The carbohydrates in bread, pasta, rice, and other carbohydrate-containing foods are long chains of simple sugar molecules. These longer molecules must also be broken down by the body.

If an enzyme needed to process a certain sugar is missing, the sugar can accumulate in the body, causing problems

1- GLYCOGEN STORAGE DISEASES

Glycogen is a glucose polymer joined in straight chains. It can have a molecular weight of many millions.

Glycogen is the storage form of glucose and is found in abundance in the liver, muscles and kidneys.

liver: stored for replenishing blood glucose during food deprivation or stress (up to 6%)

muscle: stored for providing fuel during high intensity exercise in the cell where stored

Glycogen phosphorylase, the first enzyme in glycogen breakdown, has a different form in liver and muscle

Glycogen storage diseases are a group of inherited disorders caused by a

defect in glycogen metabolism characterized by impaired conversion of glycogen to free glucose resulting in the accumulation of normal and abnormal glycogen in tissues, leading to muscular weakness or even death.

There are many different glycogen storage diseases (also called glycogenoses), each identified by a roman numeral.

These diseases are caused by a hereditary lack of one of the enzymes that is essential to the process of forming glucose into glycogen and breaking down glycogen into glucose. About 1 in 20,000 infants has some form of glycogen storage disease.

Some of these diseases cause few symptoms; others are fatal.

Glycogen storage diseases tend to cause uric acid, a waste product, to accumulate in the joints (which can cause gout) and in the kidneys (which can cause kidney stones).

The specific diagnosis is made when a chemical examination of a sample of tissue, usually muscle or liver, determines that a specific enzyme is missing.

Treatment depends on the type of glycogen storage disease.

2- GALACTOSEMIA Galactose is a sugar that is found in

many foods. When lactose is broken down in the body, glucose and galactose are produced.

Galactose is converted into glucose in the body for energy.

Galactosemia (a high blood level of galactose) is caused by lack of one of the enzymes necessary for metabolizing galactose, a sugar present in lactose (milk sugar). A metabolite builds up that is toxic to the liver and kidneys and also damages the lens of the eye, causing cataracts.

A newborn with galactosemia seems normal at first but within a few days or weeks loses his appetite, vomits, becomes jaundiced, has diarrhea, and stops growing normally. White blood cell function is affected, and serious infections can develop. If treatment is delayed, affected children remain short and become mentally retarded or may die.

Galactosemia is detectable with a blood test. This test is performed as a routine screening test on newborns in nearly all states in the United States and particularly in those with a family member known to have the disorder.

Galactosemia is treated by completely eliminating milk and milk products—the source of galactose—from an affected child's diet.

Galactose is also present in some fruits, vegetables, and sea products, such as seaweed.

Doctors are not sure whether the small amounts in these foods cause problems in the long term.

People who have the disorder must restrict galactose intake throughout life. If galactosemia is recognized at birth and adequately treated, the liver and kidney problems do not develop, and initial mental development is normal.

However, even with proper treatment, children with galactosemia often have a lower intelligence quotient (IQ) than their siblings, and they often have speech problems.

Girls often have ovaries that do not function, and only a few are able to conceive naturally. Boys, however, have normal testicular function.

SIGNS AND SYMPTOMS

At birth: Jaundice after milk consumption

Aminoaciduria: High levels of amino acids in urine and/or plasma

Hepatomegaly Hypoglycemia Ascites - fluid

accumulation in the abdomen

High Galactose concentrations in urine

COMPLICATIONS Renal

Dysfunction Premature

Ovarian Failure Poor growth and

balance Delayed speech

development Mental

retardation Vomiting

Hepatomegaly Lethargy Diarrhea Increased

susceptibility to bacterial infections

Hemolytic anemia Cataracts Death

3- HEREDITARY FRUCTOSE INTOLERANCE

It is a rare autosomal recessive disorder of fructose metabolism.

In this disorder, the body is missing an enzyme (fructose-1-phosphate aldolase) that allows it to use fructose, a sugar present in table sugar (sucrose) and many fruits. As a result, a by-product of fructose accumulates in the body, blocking the formation of glycogen and its conversion to glucose for use as energy. Ingesting more than tiny amounts of fructose or sucrose causes low blood sugar levels (hypoglycemia), with sweating, confusion, and sometimes seizures and coma.

Children who continue to eat foods containing fructose develop kidney and liver damage, resulting in jaundice, vomiting, mental deterioration, seizures, and death. Chronic symptoms include poor eating, failure to thrive, digestive symptoms, liver failure, and kidney damage.

The diagnosis is made by: DNA Testing which is A rapid, non-invasive test that requires only a small blood sample, Liver Biopsy Testing for assaying of aldolase, Fructose Tolerant Testing and Hydrogen Breath Test

Treatment involves excluding fructose (generally found in sweet fruits), sucrose, and sorbitol (a sugar substitute) from the diet.

Acute attacks respond to glucose given intravenously; milder attacks of hypoglycemia are treated with glucose tablets, which should be carried by anyone who has hereditary fructose intolerance.