71
Disorders of Carbohydrates Metabolism
Galactosemia
In 1908, von Ruess an European scientist first described the galactosemia belongs
to the class of disorders in carbohydrate metabolism. Galactosemia is a rare genetic
disorder in which patient’s body become unable to metabolize blood galactose into
monosaccharides [9]. In young mammals this is more significant because the main
disaccharide in milk is lactose which is hydrolyzed into glucose and galactose,
respectively. Galactosemia in its severe condition can affect many organs including
brain and cause mental retardation. The disease can also cause life threatening conditions and lose of ability of many tissues to perform its function [10].
There are three types of inherited galactosemia. Type I galactosemia is classic
galactosemia which is caused by deficiency in enzyme activity of galactose-1phosphate uridylyltransferase (GALT) [11]. Type II galactosemia and type III galactosemia caused by deficiency of enzyme galactokinase (GALK) and galactose
epimerase (GALE). Classic galactosemia is an autosomal recessive disease and
more than three hundred variations have been discussed in GALT enzyme [12].
Main Pathway of Galactose Metabolism
Galactose metabolism pathway is also known as Leloir pathway named after Luis
Federico Leloir in which α-D-galactose is metabolized by three enzymes in three
steps as shown in Fig. 4.1.
• In first step, α-D-galactose is metabolized by GALK into
galactose-1-phosphate.
• Secondly, GALT converts galactose-1-phosphate and UDP-glucose into α-Dglucose-1-phosphate and UDP-galactose.
• In the last step, GALE is required for interconversion of UDP-galactose into
UDP-glucose.
Table 4.1 Major classes of inherited metabolic diseases (IMDs)
Disorders
Examples
Disorders of carbohydrates metabolism Galactosemia, glycogen storage diseases
Disorders of amino acid
Alkaptonuria (AKU), Phenylketonuria (PKU),
Homocyteinuria
Lysosomal storage disorders
Lysosomal storage diseases
Disorders of purine and pyrimidine
metabolism
Lesch-Nyhan syndrome (LNS)
Disorders of peroxisomal function
Zellweger syndrome
Disorders of steroids metabolism
Congenital adrenal hyperplasia
Disorders of mitochondria
Kearns-sayre syndrome
Disorders of porphyrins
Acute intermittent porphyrias
4 Inherited Metabolic Disorders: A Current Status
Disorders of Carbohydrates Metabolism
Galactosemia
In 1908, von Ruess an European scientist first described the galactosemia belongs
to the class of disorders in carbohydrate metabolism. Galactosemia is a rare genetic
disorder in which patient’s body become unable to metabolize blood galactose into
monosaccharides [9]. In young mammals this is more significant because the main
disaccharide in milk is lactose which is hydrolyzed into glucose and galactose,
respectively. Galactosemia in its severe condition can affect many organs including
brain and cause mental retardation. The disease can also cause life threatening conditions and lose of ability of many tissues to perform its function [10].
There are three types of inherited galactosemia. Type I galactosemia is classic
galactosemia which is caused by deficiency in enzyme activity of galactose-1phosphate uridylyltransferase (GALT) [11]. Type II galactosemia and type III galactosemia caused by deficiency of enzyme galactokinase (GALK) and galactose
epimerase (GALE). Classic galactosemia is an autosomal recessive disease and
more than three hundred variations have been discussed in GALT enzyme [12].
Main Pathway of Galactose Metabolism
Galactose metabolism pathway is also known as Leloir pathway named after Luis
Federico Leloir in which α-D-galactose is metabolized by three enzymes in three
steps as shown in Fig. 4.1.
• In first step, α-D-galactose is metabolized by GALK into
galactose-1-phosphate.
• Secondly, GALT converts galactose-1-phosphate and UDP-glucose into α-Dglucose-1-phosphate and UDP-galactose.
• In the last step, GALE is required for interconversion of UDP-galactose into
UDP-glucose.
Table 4.1 Major classes of inherited metabolic diseases (IMDs)
Disorders
Examples
Disorders of carbohydrates metabolism Galactosemia, glycogen storage diseases
Disorders of amino acid
Alkaptonuria (AKU), Phenylketonuria (PKU),
Homocyteinuria
Lysosomal storage disorders
Lysosomal storage diseases
Disorders of purine and pyrimidine
metabolism
Lesch-Nyhan syndrome (LNS)
Disorders of peroxisomal function
Zellweger syndrome
Disorders of steroids metabolism
Congenital adrenal hyperplasia
Disorders of mitochondria
Kearns-sayre syndrome
Disorders of porphyrins
Acute intermittent porphyrias
4 Inherited Metabolic Disorders: A Current Status