DISORDERS RELATED TO GALACTOSE METABOLISM

PRESENTED BY:BINDU JACOB

Introduction

• Galactose is a simple sugar 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 purpose in the Leloir pathway.

SOURCES

• Dairy products• Fruits• Vegetables

Normally when a person consumes a product that contains lactose (eg: dairy products such as milk,cheese,butter), the body breaks the lactose down into galactose and glucose.

GALACTOSE METABOLISM PATHWAY

WHAT IS GALACTOSEMIA?It is a rare genetic metabolic disorder that affects how the body processes a simple sugar called galactose.Inability of the body to use galactose to produce energy.

3 inborn errors related to galactose metabolism:

1. Galactose-1-phosphate uridyltransferase deficiency

2. Galactokinase deficiency3. Uridine diphosphate-galactose 4-epimerase

deficiency

CLASSICAL GALACTOSEMIA (GALT)

Galactosemia is due to deficiency of the enzyme galactose 1-phosphate uridyltransferase.It is a rare congenital disease in infants, inherited as autosomal recessive disorder.Mutation in the GALT gene located on chromosome 9 is responsible for this disorder.

1. Galactose metabolism is impaired leading to increased galactose levels in blood (galactosemia) and urine (galactosuria).

2. Accumulated galactose is diverted for production of galactitol by the enzyme aldol reductase. Galactitol has been implicated in the development of cataract.

3. The accumulation of galactose 1-phosphate and galactitol in various tissues like liver, nervous tissue, lens and kidney leads to impairment in their function.

4. The accumulation of galactose 1-phosphate in liver results in the depletion of inorganic phosphate for other metabolic functions.

CLINICAL SYMPTOMS:• Weight loss (in infants)• Hepatosplenogamy• Jaundice• Mental retardation• Severe cases : cataract, amino aciduria and

albuminuria.

DIAGNOSIS:Early detection of galactosemia is possible by measuring the activity of galactose 1-phosphate uridyl transferase in erythrocytes.Genetic screening test done.

TREATMENT:Supplying diet deprived of galactose and lactose.

GALACTOSE KINASE DEFICIENCY (GALK)

• Defect in the enzyme galactokinase responsible for phosphorylation of galactose.

• Mutation in GALK1 gene.• Galactose is shunted to the formation of

galactitol.• Cataract development at a very early age,

sometimes within an year after birth.• Treatment involves removal of galaatose and

lactose from the diet.

URIDINE DIPHOSPHATE GALACTOSE 4-EPIMERASE DEFICIENCY (GALE)

• Extremely rare.• Mutations in GALE gene is responsible.• Symptoms vary from mild to severe and can

include cataracts, delayed growth and development, intellectual disability, liver disease and kidney problems.