Those genetic killers

Some rarest of rare diseases have been slowly but silently creeping up the medical charts in India. Doctors are as clueless about their diagnosis and treatment as they are alarmed about their occurrence. For those who get such rare disorders, life falls apart not just for the victim but the family too. Treatments, if any, are available only in the US and are out of most pockets. Nidhi Mittal meets up with some of the families tackling rare diseases like Gaucher, MPS and Pompe

They are the flavour of Bollywood now-a-days. If Aamir Khan brought the Dyslexics into news through Taare Zameen Par, Big B Amitabh Bachchan made your heart beat for people with Progeria. Next, Shah Rukh got the Asperger syndrome in My Name Is Khan and now we’re waiting to see Hrithik Roshan as a paraplegic in Sanjay Leela Bhansali’s Guzaarish.
It may help directors and actors looking for the next idea in this genre to read about Pompe, Gaucher or MPS. These are the three rarest of rare diseases people have been getting, but you may be surprised to know that there are around 8,000 known rare ailments in the world.
Unheard of, and with very little awareness about them, Pompe, Gaucher and MPS come as a shock to people who get into their trap – either by suffering themselves or carrying the burden of an affected child. The latter is the sad story of Mr and Mrs Prasanna Shirol.
“It was the biggest shock ever. I didn’t understand what the doctor was saying. I had never heard of it before even though I had started suspecting my daughter was ailing of something big,” says Prasanna, Nidhi’s father. Nidhi, 10, suffers from Pompe, a rare disease that causes muscle weakness, poor muscle tone, an enlarged liver and serious heart defects in infants and juveniles, leading to an early death.
Nidhi has never played outside her home in Bangalore with other children of her age. In Class IV now, her mother accompanies her to the school, carries her to the first floor where her classroom is and sits outside waiting for the bell to ring everyday. Unable to even walk or stand, Nidhi stays indoors after returning home. Her physiotherapist and two friends, who come to play with her only if they don’t want to play outside, are her slimline visitors.
Nidhi, who is put on a ventilator every night, can’t watch TV for more than half-an-hour as that stresses her out. And her slow speed at homework leaves her with no time to pursue her only hobby — painting. “I love drawing but I have to do my exercises, homework, have dinner and go to sleep on time. So I have no time for it now,” Nidhi tells you in a tone that makes you feel she is having difficulty in talking. It takes time to understand her garbled diction.
She insists she wants to be a doctor and treat people in pain like her. Interrupting her on a usual weekday evening while she is doing her English homework, one asks her if she finds it difficult to go to school and pat comes the reply, “I love school and my friends. I don’t take leave unless I am feeling very unwell. I love my class teacher. She talks sweetly to me,” says the child, whose favourite subjects are Maths and Science and likes eating dosa.
“The teachers and students in her school are very co-operative. They don’t treat her any differently. They also let me use the library as I have to spend my entire time there. Though she manages to stand up for a few minutes, she is very slow at other activities. To prevent her from getting infections we can’t take her outside. She spends time watching Discovery and Nat Geo channels and playing with her two friends. The last film she saw was Paa and she loved it. All that we now wish is that she is able to fend for herself when we are not there,” Nidhi’s mother Sharda tells you.
Sharda and Prasanna are brave parents tackling the situation with a smile. They have a next to nothing social life as their time passes in looking after Nidhi whose needs are big. “There’s no free time. I go to school with her and at home have to make sure her daily regimen is followed like clockwork,” Sharda says.
Life has not been easy for this couple. Sharda had to abort her second child as pre-natal tests confirmed the same disorder. That was three years back, and now the couple doesn’t want to take a second chance. “It scares us to think that our second child may also suffer the way Nidhi does,” Sharda says, though going by the textbook, there are 75 per cent chances that their next baby would be normal, with pre-conception medication. “We will just live for Nidhi and her well-being,” she says.
Though Nidhi was born a normal child in 1999, there was a considerable delay in milestones like crawling and standing. She was already two years old and had still not started walking. A worried Prasanna took her to a pediatrician, who said there was nothing to worry about as a few children take time. Unconvinced, he took Nidhi to NIMHANS where the doctor conducted tests and termed her illness as Glycogen Storage Disorder Type II, or Myopathy with no cure.
Nidhi’s muscles got harder and she started facing respiratory problems. Though she could walk till she was seven, a serious respiratory attack made her condition critical and she had to be hospitalised and put on ventilator. Tests then determined that she actually suffered from Pompe, a type of Lysosomal Storage Disorder (LSD), one of the 15 categories of rarest of rare diseases.
“I read up a lot on the disease and found that there was no drug to treat this disease. However, in 2008, a drug called Myogen came in but only in the US, that too at a very high price. Only one company — Genzymes Corporation — sold it. Though there was a charity scheme to provide the dose free, it favoured only children less than a year old. I got in touch with the International Pompe Association as there was no office in India. Fortunately, I convinced them about my daughter’s case and they made it free for her,” Prasanna says.
Enzyme Replacement Therapy alone costs Rs 8 lakh a month, with one infusion needed after every 15 days in a patient like Nidhi.
Nidhi got her first medicinal infusion in April 2008, two years after she was diagnosed with Pompe. What delayed her early treatment was the doctors’ lack of awareness and a late diagnosis. “People come to Delhi from across India with such rare diseases because not many hospitals have the facility to diagnose them. Specialised tests like urine metabolic test, MPS quantification, electro-therasis and enzyme analyses of the blood are unavailable at most hospitals. A majority of such diseases manifest themselves in the first two years of life. We need to get to the bottom of the genetic disorders but this will not happen till genetics becomes a college subject,” Dr Ratna Puri, consultant, Department of Genetics, Sir Gangaram Hospital, explains.
In simple terms, Pompe is an inherited disorder caused by the build-up of a complex sugar called glycogen in the body’s cells. The accumulation of glycogen in certain organs and tissues, especially muscles, impairs their ability to function normally. Researchers have described three types of Pompe syndromes which differ in severity and the age at which they appear. They are known as classic infantile onset, non-classic infantile onset and late-onset.
Nidhi’s is the non-classic form of infantile onset Pompe disease. It is characterised by delayed motor skills (such as rolling over and sitting) and progressive muscle weakness. The heart may be abnormally large but affected individuals normally do not experience heart failure. The muscle weakness in this disorder leads to serious breathing problems and most children live only into early childhood. “Pompe doesn’t affect the brain and that’s why the enzyme replacement therapy works. Difficult to avail unless the company sponsors it, the therapy doesn’t work for rare LSD diseases which affect the brain also, like the MPS-II. Nidhi is showing good improvement with the vials she takes every 15 days, but there was a time when she was hardly expected to survive,” Dr ML Kulkarni who diagnosed the disorder in Nidhi, says.
A pediatrician with special interest in genetics for the last 30 years, Dr Kulkarni of the JJM Medical College, Davangere, however, says that the company supplying drugs free of cost is misleading patients. “Companies are attracting people by offering incentives. They are giving the treatment free for eight to 10 years but it is a lifelong treatment. After that period is over, they will have to pay for the expensive therapy, and not many can afford it. Hopefully, 10 years from now, we may have cheaper drugs or better treatment,” he says. Genzymes provides free medication to about 70 patients across India.
Prasanna says there are six known Pompe cases in India and it’s a life threatening, debilitating disease which can cause an early death if it goes untreated. It affects the normal growth of a child, so much so that the patient also finds it difficult to hold his head, says Prasanna, talking about a film released in the US — Extraordinary Measures. Starring Brendan Fraser and Harrison Ford, it is a true story of a parent trying to save his two Pompe daughters.
Saying he was lucky to have found the information and drug for his daughter in time, Prasanna feels it is important to spread awareness among uninformed people. “I got in touch with several doctors who saw patients with rare diseases. Finally in September 2009, eight people from different States came together to form the Lysosomal Storage Disorder Support Society of India (LSDSSI), of which I am the President. We observe February 28 as the International Rare Disease Day,” he tells you.
It was through this society that one came across Delhi-based Manjit Singh whose two sons suffer from yet another rare disease called the Mucopolysaccharidoses or MPS.
Nineteen-year-old Prateek and 17-year-old Pradeep were diagnosed with MPS-1, a rare genetic progressive disorder in 1995. However, it was only in 2006 and several doctors, diagnosis and tests later that it was concluded that they suffer from MPS-2, a very severe disorder.
Manjit has not been able to get proper treatment for his sons as the therapy costs him Rs 2 lakh per infusion for one son. An infusion is needed every 15 days, which means Rs 8 lakh a month for his two children on just infusions.
He has not been able to get a sponsored treatment so far as his sons have grown up and the global charity favours only younger children. Both brothers are short with Prateek standing at 136 cm and Pradeep at 134 cm. They suffer from hearing problems (especially in winters), insomnia, hernia (for which they have been operated), brittle skin and hair, among other issues.
Born normally to normal parents, Prateek started getting skinny when he was five. The parents thought it to be routine weight loss during growing years. When Manjit noticed a defect in Prateek’s gait and his fingers concaving, not allowing him to open up his palm completely, he took him to an orthopaedic who said the child had tight bones, nothing more serious.
“Then his vision started blurring but even the opthalmologist felt it was not something serious. Next, a cardiologist found leakage in one valve and an enlarged heart. He was the one who first suspected MPS. In 1995, we went to Sir Gangaram Hospital which didn’t have the equipment to conduct confirmatory tests so we went to AIIMS where MPS-1 was confirmed. My younger son was two then and doctors told us to test him too. He, too, tested positive,” Manjit recalls.
Till 1999, there was no treatment available for MPS-1. The condition of the brothers kept getting worse and in 2006 it came out that they actually suffered from a more serious disorder, MPS-2. By that time, both had had hernia on both sides and had been operated on one side. Pradeep had a leakage in the heart. MPS-2 damages the patient both physically and mentally. They stop growing physically but their organs grow normally leaving little space in the body, causing multiple problems.
In this rare disease, bones become so weak that fractures occur without any stress. In 2008, Pradeep suffered a “pseudo-fracture” of the hip which took him months to recover. “It all happens due Vitamin D and Calcium deficiency,” Manjit, co-ordinator and treasurer of the LSDSSI, says.
Manjit’s problems had just begun. In August 2009, Prateek had a pulmonary spasm which didn’t get detected in the X-ray but damaged his heart. He fell unconscious, was put on a ventilator and doctors all but gave up on him. However, he was destined to live.
The two brothers no longer go to school, having left studies four years back, after Class X. They studied normally till Class V but were promoted in the next three classes to keep up their morale. Their condition had a fallout on their behaviour. They wouldn’t go alone anywhere and found it hard to gel with classmates. The parents finally decided to keep them at home though they insist that the people at school were kind and co-operative.
“They are jovial boys. Prateek spends time watching TV. He likes old films and is an Amitabh and Dharmendra fan. Pradeep, on the other hand, is an Internet and video games buff. He plays PS-3 the day long and manages some badminton too,” Manjit says. At age 17 and 19, the boys love watching cartoon films and children’s shows like Son Pari and Shararat.
Manjit tells you that there are three lakh LSD patients in India. LSD is a group of 40 genetic rare disorders of which MPS is most common. Dr Kulkarni who comes across three cases of Pompe and two cases of Gaucher a year, witnesses almost 20 cases of MPS annually, says South India is high on genetic disorders majorly because people marry among blood relatives.
“Inbreeding is common in Andhra Pradesh, Karnataka etc, while its only two per cent in north India. Parents are the carriers of the bad gene which is one in a lakh people,” he says.
By gaucher!
Twenty-year-old Shashank Tyagi is finally leading a normal life. He is not in pain anymore, goes to college, meets people and hangs out with friends often. It was nothing like this till four years back. From age five, he started facing problems, the cause of which no one could determine. His spleen increased along with the liver, he became over-weight and had a protruding abdomen; eye sight became very weak and bones fragile with him fracturing his left hand without any apparent stress. All this while Shashank took ayurvedic treatment which showed no results.
A resident of Ghaziabad, Shashank was taken to the Kalavati Hospital in 1998. He underwent tests but doctors couldn’t pinpoint the cause of his problems and vaguely suggested a bone marrow surgery. “It’s a painful process and so I didn’t go for it. I went back to ayurveda which provided no relief. In 2004, I went to AIIMS because my liver had enlarged and I had started throwing out whatever little I was eating. My BP dipped and haemoglobin was as low as 8,” Shashank recalls. And, he was only 4 feet tall.
In AIIMS he was diagnosed with Gaucher Type-1. The treatment was too expensive, so Shashank helplessly carried on with ayurveda. He then got to know about the Christian Medical College in Vellore where Dr Sumita Danda, professor in clinical genetics, had been dealing with rare cases. “I owe it to her as she was the one who told me that bone marrow surgery was not required and referred me to the global charity. That’s how I could get medicines free. I had my first infusion in 2006 and I am feeling much better since 2007,” Shashank says. He now weighs 48 kg and is 162 cm tall.
“Gaucher has been there for a long time, but it’s only now that we can detect it with the help of clinical genetics. The enzyme test critical to diagnose rare diseases is available in either CDFD, Hyderabad, or Sir Gangaram Hospital, Delhi. Due to lack of research, the treatment is difficult. Genzym Corporation provides free medicines. Recently an eight-year-old Gaucher patient has got it,” Dr Danda tells you from Vellore. Gaucher is an inherited disorder affecting many organs and tissues. Symptoms vary widely. There are three types of Gaucher of which Type1 is common. Main signs include enlargement of liver and spleen, low red blood cells, easy bruising due to decreased platelets, lung ailments, fractures and arthritis.