doi:10.1038/nindia.2012.158 Published online 26 October 2012
Researchers have identified new genetic mutations in Indian newborns afflicted with galactosemia. Newborns with galactosemia are unable to fully break down the simple milk sugar galactose. The mutations disrupt the activity of a gene that codes for galactose-1-phosphate uridyl transferase (GALT), an enzyme that facilitates galactose metabolism.
This study raises the prospect of genetic screening for Indian galactosemia patients, allowing early diagnosis and therapy.
Infants with galactosemia lack activity of the GALT enzyme due to mutations in the GALT gene, leading to a build-up of galactose-derived substances that damage the liver, brain, kidneys and eyes. In Western countries, newborns are routinely screened for the presence of genetic disorders like galactosemia. Besides lacking such newborn screening programmes, no studies have thrown light on the link between mutations in the GALT gene and galactosemia in the Indian population.
To pin down new mutations in Indians, the researchers selected 450 Indian infants with cholestasis, a disorder in which the flow of bile from the liver is slowed or blocked. They then performed a battery of tests including abdominal ultrasonography, total blood tests, liver function tests and urine culture. Blood samples of patients showing GALT activity under 50 per cent were used for genetic analyses.
Among 450 infants with cholestasis, 55 showed GALT enzyme activity below 50 per cent. The study identified 16 mutations in the GALT gene of these 55 Indian galactosemia patients, including 10 novel mutations.
Among the novel mutations, only three (Y89H, S181F and R333L) were predicted to be damaging, while rest were predicted to be tolerable mutations. However, only two mutations (N314D and Q188R) were found to be common in Indian galactosemia patients.
"DNA analysis for most common mutations in the GALT gene can be used as a screening procedure for the early diagnosis of galactosemia, resulting in the development of an effective strategy for prevention and treatment of the disease," says lead researcher Rajendra Prasad.
The authors of this work are from: Department of Biochemistry, and Division of Pediatric Gastroenterology, Postgraduate Institute of Medical Education and Research, and Department of Physiology, Government Medical College and Hospital, Chandigarh, India.