Gene hunters: Prof. Kunal Ray (rear) and Arnab Gupta at their lab in IICB (Picture by Sanat K. Sinha)

In the beginning, attitudinal problems of his 14-year-old son didn’t appear anything wrong to Sadiur Rahman. The otherwise vivacious Anisur would frequently pick up fights in school and his grades showed a steady decline. Sadiur, a brick-trader near Diamond Harbour, 60 kilometres away from Calcutta, thought it was a sign of adolescent unruliness which fades away just like acnes.

But that didn’t happen; instead, things took an unpredictable turn gradually. The boy began to fly into rage quite often and would not hesitate to hit his kid sisters. During those fits of fury he would run amok. His speech would became incoherrent, with saliva droolling off his mouth. While elders advised him to summon an exorcist, Sadiur, a science graduate, knew that Anisur’s problem had something to do with the brain.

He took his son to a doctor who promptly wrote down a prescription of antipsychotic drugs. They didn’t work, and Anisur’s condition deteriorated rapidly. Muscles in his hands and legs became weak and he had tremors.

When Anisur started developing convulsions, Sadiur couldn’t help rushing his son to the Bangur Institute of Neurology (BIN) of the SSKM Hospital.

“A sudden appearance of tremors, muscular spasticity and speech problems in the teenager pointed the needle of suspicion to a notorious hereditary disorder called Wilson’s disease,” said Dr Prashant Kumar Ganguly, the neurologist who examined Anisur at the clinic.

Ganguly and his colleague Dr Shyamal Kumar Das advised a few diagnostic tests for Anisur: an eye examination, a special type of urine test and a few blood tests. The eye test revealed a brown ring (called Kayser-Fleischer ring) in the cornea, and his urine had a high level of copper. “All the tests confirmed that an excess of copper had been accumulating in his eyes, brain, kidneys and liver,” said Das.

Because too much of the metal could damage the liver and cause a cirrhosis, a life-threatening condition, and destroy the brain and spinal cord, the doctors put Anisur on medicines that prevent copper accumulation in the body. He was also advised to keep away from food rich in copper, such as peas, beans, nuts, chocolate, whole wheat, dried fruit and liver. The drug and food regimen responded and Anisur showed slow signs of improvement.

“Although Wilson’s disease remains largely unrecognised in this country, approximately one out of 30,000 people may be suffering from the genetic disorder,” says Dr Kunal Ray, a human geneticist at the Indian Institute of Chemical Biology (IICB), Jadavpur. Neurologists at the BIN have diagnosed the disease in more than 40 people in the outpatient clinic in the past two years.

“Most of the patients die before the disease is even diagnosed,” says Ray. “And it’s a fatal illness if no treatment is offered in time.” According to him, even more worrisome is the fact that at least one in 90 people unwittingly act as carriers of an abnormal gene ? they may have mild but insignificant signs of Wilson’s. They never become ill and do not need treatment.

For people to exhibit symptoms of the disease, they must inherit two copies of the gene, one from the mother and one from the father. Which means siblings of people with the disease have one-in-four chance of getting the disease. “The specific pattern of the disease gave us the hunch that one of Anisur’s sisters might be inheriting Wilson’s,” says Arnab Gupta, a senior research fellow working with Ray.

Gupta travelled to Anisur’s home to collect blood samples from the siblings. Genetic analyses of the samples revealed that the younger sister had inherited the disorder. “Since we were able to predict the disease much in advance, before the symptoms showed up, it was possible to take preventive measures,” says Gupta. She was given a chemical called zinc acetate which checks absorbtion of copper in the stomach. Because it prevented copper accumulation in her body, she can lead a more or less normal life. Till now the IICB team has helped arrest the disease in five families.

How does the disorder originate in the genes? Why does it jeopardise copper metabolism in the body? “The responsible gene is located on chromosome 13,” says Ray. “The gene is called ATP 7B and it has several mutations that get transmitted from a generation to the next.”

Like vitamins, copper is an essential micronutrient required by our body for normal metabolic processes. Usually, the body needs about four milligrams of the metal daily. However, if there is an excessive supply of the metal, it’s flushed out by the liver through bile (greenish-brown fluid secreted by the liver) in the excreta. “In Wilson’s disease the flushout mechanism goes awry because of the faulty gene,” says Ray. Usually, the disease manifests as either a recalcitrant liver disease or a neurological disorder. Ray and his colleagues have identified common mutations specific to Indians after having studied 62 patients and their 200 relatives. The study was published in a recent issue of the journal Human Genetics

The team has also discovered genetic markers which can help identify the disease much before it makes its appearance in families with a history of the disease. They are expecting to devise a blood test based on that finding, so that nobody born with Wilson’s suffers like Anisur.