In focus: Huntington’s Disease

A middle-aged taxi-driver from Tumakuru with dreams of owning a large travel agency is mysteriously afflicted by mood swings and involuntary body movements which progressively get worse.

In Andhra Pradesh, 35-year-old Raju (name changed), a state heavyweight lifting champion finds himself physically wasting away, prompting his wife to work for a daily wage in order to support the family.

In Davanagere, a woman afflicted with strange mental and physical disorders is turned out by her rural family and dies after being struck by a lorry.

In Bengaluru, a successful IT professional fears being beset by a debilitating condition which affected his mother.

While these cases may appear random and unconnected, what unites them is the fact that all four people were diagnosed as suffering from Huntington’s Disease (HD), a rare genetic, neuropsychiatric disease which largely affects Caucasians.

In India, scientists believe that between three to seven people among 1 lakh people are affected. The effect of the disease is such that the affected person usually dies within 15-20 years.

Medical professionals at Nimhans in Bengaluru, who are at the forefront of efforts to address HD, explained that the worst aspect of the disease, which has a 50% chance of being passed on to children if one parent carries a copy of the defective HD gene, is that it primarily affects people in the stride of their lives.

Doctors performing blood test at NIMHANS. DH photo.

“It usually hits people in their 30s and 40s, just when they have settled into their careers and started their families and had children. There is really no way to confirm if one is affected unless you have a test done,” said Dr Sanjeev Jain of Nimhans’ Molecular Genetics Laboratory, Department of Psychiatry, who heads a Huntington’s group at the institute, an impromptu unit created to fill a void left by a lack of governmental support.

Unrecognised in India

Officially, the government of India does not acknowledge the existence of Huntington’s, explained Vikas Bhat, a Pune resident whose wife was diagnosed with HD in 2015.

In 2017, Bhat sent a letter to Prime Minister Narendra Modi, asking that the government conduct awareness campaigns to inform the public and doctors about the disease, provide a measure of financial aid for affected families and enable greater genetic testing to catch the disease earlier.

The government’s response was to state that Huntington’s does not fall under the National Mental Health Programme, Bhat said.

“Make no mistake, the government has a rare disease policy, but few medical practitioners in India are aware of HD, and the government has not passed strict guidelines about treatment or management and so, most of the time, people are misdiagnosed or are classified as being mentally ill,” Dr Jain said.

In rural areas, where HD’s prevalence is fed by consanguineous marriages, the ramifications are worse, said Dr Nikhil Ratna, who works with Dr Jain’s group at Nimhans, explaining that ostracisation of HD families over claims of demonic possession are common.

He added that the “occurrence of Huntington’s has increased to the point that we are now seeing young children being affected as a consequence of the serial increase in a DNA segment known as the “CAG trinucleotide repeat” which “repeats from one generation to another.”

The pattern of inheritance of HDSA

This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated 10 to 35 times within the gene. In people with Huntington’s, the CAG segment is repeated 36 to more than 120 times. According to Dr Ratna, Nimhans is currently treating 12 juveniles with the disease and according to figures provided by the institute, 30 affected families are availing regular treatment at the institute out of 100 families diagnosed. Dr Jain added, however, that the true number of affected is larger and unknown, primarily because of a lack of awareness and poor diagnosis.

“The burden of the disease is high and is expected to rise many-fold in the years to come. The impact on families can be devastating,” Dr Ratna said.

No one knows this better than Arjun Joshi, (name changed) a financial expert employed in Bengaluru’s IT industry who has been living with Huntington’s in some form or fashion since childhood. His mother and her sisters have the disease, and in 2014, Joshi, who is married with two children, discovered that he too had it.

The revelation set him off on a travel spree, because, as he told DH, “I felt I had to live for the moment.” These days, he volunteers at an old-age home to help people and to avoid thinking about his condition.

When asked about whether he worried if the disease would pass on to his children, he choked up. “That is the worst thing about Huntington’s... is the fact that members of the next generation may one day suffer from this disease through no fault of their own. It is not a good feeling to know that,” he said.

What’s next?

Few have easy answers for the sense of helplessness and moral self-castigation experienced by Joshi and others. In the case of the heavy-weight lifter, Raju, who has since died, the disease has passed on to his juvenile son. Now 16, he is largely immobile and unable to communicate.

Officially, there is no cure for the disease, but the HD community has pinned its hopes on a new medical breakthrough which involves injecting short RNAi into the patient’s spinal fluid to destroy the HTTA RNA mutation that causes Huntington’s.

Human trials are currently underway in Europe, but with the process expected to take five years, it could take many more years before it came to India, Dr Jain said. With the formation of a Huntington Disease Society of India (HDSI) on August 16, 2019, however, patients and doctors see a way to champion their problems and get more support from the government and institutions. “There is hope for the future, but much work needs to be done and the government must get involved. Considering that Bengaluru is a biotechnology hub filled with myriad talent, we should be considering developing our own homegrown solutions,” Dr Jain said.