Disturbances in Carbohydrate Metabolism

Mohd.Toufeeq

What are Carbohydrates?

Carbohydrates are composed of carbon,hydrogen and oxygen. The name carbohydrates literally means hydrates of carbon. They may be defined as polyhydroxyaldehydes or ketones or compounds which produce them on hydrolysis.

Functions of carbohydrates
Most abundant dietary source of energy.

Precursors for many organic compounds(fats,amino acidS,etc.) Structural components of many organisms like cellulose in plants, exoskeleton of some insects,etc. Also serve as the storage form of energy(glycogen) to meet the immediate source of energy demands of the body.

Classification of Carbohydrates
Carbohydrates are broadly classified into three groups: 1. Monosaccharides-composed of a single monosaccharide unit. Eg:Glucose,Frutctose. 2. Oligosaccharides-compose of 2-10 monosaccharide units. Eg:Maltose,Lactose,Surcose 3. Polysaccharides-polymers of several monosaccharide units.

 Polysaccharides are of two types: 1. Homopolysaccharides-composed of only a single type of monosaccharide. Eg:Starch,dextrins,inulin,glycogen,etc. 2. Heteropolysaccharides-composed of a mixture of a few monosccahrides. Eg:Mucopolysaccharides:Hyaluronic acid,heparan sulfate,chondroitin sulfate and keratan sulfate.

Normal Carbohydrate Metabolism

Mucopolysaccharidoses
MPS result from abnormal degradation of glycosaminoglycans like dermatan sulfate,keratan sulfate,heparan sulfate and chondroitin sulfate. This results in organ accumulation and eventual dysfunction. The catabolic enzymes involved in the breakdown of glycosaminoglycans are deficient. Organs involved:brain,liver,heart,spleen and blood vessels.

Clinical Presentation
MPS type I includes Hurler,Hurler-Scheie,and Scheie syndromes.

MPS type I H (Hurler syndrome) MPS type I H/S. This form is intermediate between the Hurler and Scheie syndrome. MPS type I S (Scheie syndrome). Biochemical findings are identical to type I Hurler syndrome, but clinical features are less severe.

Hurlers Syndrome
It is a disturbance of mucopolysaccharide metabolism characterized by an elevated mucopolysaccharide excretion level in urine. Large head Prominent forhead, broad saddle nose,wide nostrils,hypertelorism,puffy eyelids,thick lips,large tongue,nasal congestion. Short neck with spinal abnormalities. Flexion contractures result in the claw hand. Dwarfism with mental retardation. Corneal clouding and hepatosplenomegaly are classical manifestations

Clinical features

Oral manifestations

Shortening and broadening of mandible. Greater than normal distance around the arch from ramus to ramus accounting for the spacing of the teeth.
Localized bone destruction in the jaws.

Small teeth which are widely spaced. Gingival hyperplasia.

Histologic features
Excessive accumulation of mucopolysaccharide in tissues and organs throughout the body like liver, spleen,cartilage,bone,heart,etc. Abnormal deposits with involved fibroblasts appear as clear or gargoyle cells. These cells are large with metachromatic cytoplasm and crescent shaped nuclei.

Treatment
There is no treatment for the disease. Death usually occurs at the age of 10.

Lipoid Proteinosis
It is a rare, autosomal recessive disorder exhibiting generalized thickening of skin,mucosae,and certain viscera. Beaded eyelid papules Laryngeal infiltration leading to hoarseness of voice. Inability of infants to cry at birth due presence of wihte plaques in the epiglottis,aryepiglottic folds, and interarytenoid region.

Clincal features

 Other mucocutaneous changes include: Thickening of tongue and freunlum. Blisters. Warty skin papules. Scar ring. Alopecia. Dental anomalies.

Histologic Features
Widespread depostion of hyaline(glycoprotein) material.

Disruption of basement membrane. Ultrastructural examination reveals concentric rings of excess basement membrane surrounding blood vessels. Hyaline deposits consist of hyaluronic acid, chondroitinsulfate with large amount of lipids.

Treatment
There is no treatment for the disease.

Hereditary Fructose Intolerance

Over 25 years ago Chambers and Pratt reported an unusual case of a woman who became nauseated and committed after ingesting fruit or sugar. This was later diagnosed as hereditary fructose intolerance.

Clinical Features
Transmitted as an autosomal recessive trait. Hypoglycemia Vomiting after ingestion of fructose-containing foods. Results from a deficiency in fructose 1-phosphate aldolase. Affected individuals rapidly acquire an intense aversion to all sweets and fruits.

Oral Manifestatations
Subjects with hereditary fructose intolerance had a total sucrose intake of less than 5% of that of controls. Caries scores(DMFS) were less than 10% of those of controls. Treatment Treatment is with a fructose free diet, which if adhered to, is concordant with a good prognosis.

Essential Fructosuria
This occurs due to deficiency of the enzyme hepatic fructokinase,fructose is not converted to fructose 1phosphate. This is a asymptomatic condition. There is excretion of fructose in urine. Treatment involves the restriction of dietary fructose.

Glycogen storage disorders

The metabolic defects concerned with the glycogen synthesis and degradation are referred to as glycogen storage disorders. A few examples: Fasting hypoglycemia: Due to defect in the enzyme glucose 6-phosphatase,enough free glucose is not released from the liver into blood. Lactic acidemia: Glucose is not synthesized from lactate produced in muscle and liver. Lactate level in the blood increases and the pH is lowered (acidosis)

 Hyperlipidemia: There is a blockade in gluconeogenesis. Hence more fat is mobilized to meet energy requirements of the body. This results in increased plasma free fatty acids and ketone bodies. Clinical features Constant hunger and need to eat often Easy bruising and nosebleeds Fatigue Irritability Puffy cheeks, thin chest and limbs, and swollen belly

Treatment
The primary treatment goal is prevention of hypoglycemia and the secondary metabolic derangements by frequent feedings of foods high in glucose or starch (which is readily digested to glucose).

To compensate for the inability of the liver to provide sugar, the total amount of dietary carbohydrate should approximate the 24-hour glucose production rate.

Galactosemia
Galactosemia is a condition in which the body is unable to use (metabolize) the simple sugar galactose. It occurs in approximately 1 out of every 60,000 births among Caucasians. The rate is different for other groups.
Persons with galactosemia cannot tolerate any form of milk (human or animal).

Galactose makes up half of lactose, the sugar found in milk. The other sugar is glucose. If an infant with galactosemia is given milk, substances made from galactose build up in the infant's system. These substances damage the liver, brain, kidneys, and eyes

Clinical Features
Convulsions Irritability Poor feeding (baby refuses to eat formula containing milk) Yellow skin and whites of the eyes (jaundice) Vomiting Hepatomegaly Lethargy
Poor weight gain

Treatment
The only treatment for classic galactosemia is eliminating lactose and galactose from the diet. Even with an early diagnosis and a restricted diet, however, some individuals with galactosemia experience longterm complications such as speech difficulties, learning disabilities, neurological impairment (e.g. tremors, etc), and ovarian failure in females.

References
Shafers Textbook of Oral Pathology-6th edition

U.Satyanarayana Textbook of Biochemistry-3rd edition