Inborn Errors of Metabolism- Galactosemia

INBORN ERRORS OF METABOLISM- GALACTOSEMIA

Galactosemia is an inherited autosomal recessive disorder in which the body is not able to metabolise the simple sugar, galactose into glucose. The alternative names for this disease is This disease has a frequency of 1 in 60000 (Longo et al. 2004). This disorder is mainly caused by the deficiency of galactose-1-phosphate uridyltransferase(GALT) that result in the buildup of galactose-1-phosphate (gal-1-phosphate) in the blood. Galactokinase (GALK) is the enzyme responsible for converting galactose into gal-1-phosphate (Boxer et al. 2011).

Galactose is a simple sugar which is found in milk and dairy products. When a patient is given milk or dairy product which contains galactose, galactose-1-phosphate, and galactose, galactitol and galactonate builds up in the patient's system and damage the liver, brain, kidneys and eyes. These patients have very low tolerance towards milk or dairy products. Usually galactosemia is observed in infants and newborns (Longo et al. 2004). It has been known that this disease is a potential lethal disorder (Boxer et al. 2011).

Abnormal protein glycosylation has been detected in patients with galactosemia and this may explain the abnormality in the brain and ovarian development (Longo et al. 2004).

GENETICS

Galactose-1-Phosphate + Uridine 5'-Diphosphoglucose Glucose-1-Phosphate + Uridine Diphosphogalactose

Uridine Diphosphogalactose Glucose-6-Phosphate

(Longo et al. 2004)

Galactokinase converts galactose to galactose-1-phosphate. GALT enzyme is the second enzyme in the Leloir pathwat that converts galactose-1-phosphate (gal-1-phosphate) to uridine diphosphogalactose (UDP-gal) and uridine diphosphoglucose (UDP-glu) to glucose-1-phosphate (glu-1-phosphate). The high levels of gal-1-phosphate is due to the deficiency in GALT enzyme that cannot convert gal-1-phosphate to UDP-gal.

Galactosemia is caused by mutation in the genes that makes GALT. The gene is located in the short arm of chromosome 9. The mutation that occured in known as Q188R mutation. An experiment was done in which human GALT cDNA containing the Q188R mutation was expressed in "knockout" yeast cells, and there was no GALT activity detected (Lai & Elsas 1998). Mutation in this gene causes the enzyme to work poorly or not at all. Due to this mutation, the GALT enzyme is unable to metabolise galactose to glucose thus causing accumulation of galactose in the body. Carriers of galactosemia do not have the symptoms, but have one normal GALT gene and one abnormal GALT gene. About 1 in 100 people are carriers of GALT mutation (Lai & Elsas 1998).

MAJOR FINDINGS

Galactosemia means "galactose in the blood". A. Von Reuss made the first report on galactosemia in 1908. He found the presence of galactose in the urine of an infant. This is known as galactosuria. He also observed enlarged liver and spleen of the infant. Eventhough scientist have discovered galactosemia disorder, the defective