Navigating diagnosis and care for Rare Eye Disease is complicated and complex. It can take many years and the burden of care on the family is huge. Families also deal with many socio-economic challenges apart from the lack of effective treatment options. We speak with fathers of children living with rare diseases and Dr. Muralidhar Ramappa, Consultant Opthalmologist, L V Prasad Eye Institute (LVPEI)
Panelists:
Speakers - Dr. Muralidhar Ramappa, Consultant Opthalmologist, L V Prasad Eye Institute (LVPEI)
Mr. Nirav Shah: Father of a child living with nephropathic cystinosis
Mr. Kalpesh Suratwala: Father of child living with MPS, mucopolysacchoridosis
Moderated by Aparna Mittal and Dr. Shital Raval Patel
What is a rare disease and how it is different from an eye related complication of a rare disease?
A rare disease is typically defined as a condition that affects a relatively small number of individuals. The prevalence of rare diseases can vary depending on the geographic region. For example in Europe, a disease is considered rare if it affects one in every 2000 people. Despite their rarity, when considered cumulatively, rare diseases impact a significant portion of the population. In the U.S., approximately 90 million cases of rare diseases have been reported to date. Rare disease pose a significant burden on family and society. Many rare diseases lack conclusive diagnosis and effective treatments and lead to distress and uncertainty for affected individuals and families.
Rare eye disease primarily involves the eyes and can lead to vision impairment or blindness. Retinitis pigmentosa, Usher syndrome – a part of retinitis pigmentosa, cone dystrophy including color blindness, keratoconus and corneal dystrophies are common rare eye conditions. Whereas in systemic rare diseases with eye complications, multiple organs and systems in the body and the eyes are affected during disease progression. Metabolic diseases or storage diseases are considered as rare diseases. Globally, over 7000 rare diseases have been identified, with around 900 of them having ocular implications. In India alone, databases indicate about 400 rare ophthalmic conditions. The main challenge with rare diseases is the long time needed for an accurate diagnosis. Many rare diseases have no cure, and only symptom management through palliative care is possible.
What is the defined protocol for diagnosis of rare disease in India?
In India, the diagnosis process of rare diseases requires collaboration among multidisciplinary team of specialists trained in systemic disease, including those affecting the eyes and other specific organs to ensure accurate diagnosis. This process is time consuming and challenging. Approximately 95% of rare diseases have a genetic predisposition. Role of genetic counsellor is crucial in provide guidance to patients and families regarding the genetic aspect of disease. Depending on the condition, metabolic experts or neurologists may also be involved. Molecular screening is important for confirming the diagnosis. After the diagnosis is confirmed, a treatment protocol is decided including a curative approach, symptom management and addressing complications.
Kalpesh, Can you share what your son’s condition is, when he was diagnosed and the early signs that led to his diagnosis?
Initially we did not notice any issues with our child. Everything seemed fine until he was around 3-4 years old. He was not even 5 years old when he got diagnosed with MPS. We were also not aware of the signs and seriousness of the condition. Our focus was on finding a cure for MPS. Additionally we consulted a genetic counsellor, but they did not find any cure. We also don’t have any family history of the disease.
It was actually through his school, we first got to know that he is having trouble with his vision. A teacher informed us and we took it seriously. He was quite shy and did not share his difficulties with us when he started school. We consulted every eye specialist in the city. But, they could not offer any appropriate treatment or surgery. Eventually a local doctor with thorough research, recommended a specific surgery and referred us to Dr. Murali at LVP Eye Institute. We proceeded with the surgery suggested as the best option and it improved my son’s eyesight more than we had expected. After the surgery he experienced redness and infections in his eyes for about 3 to 4 years. Overtime those issues improved and now his eyesight is in much better condition. His eye problems are under control while other symptoms still persists. For instance, he had hernia operation but still suffers from muscular problems. He is not able to hold objects properly or walk properly because of that. His heart is only functioning at 50% capacity. We are still exploring better options to improve his condition.
Dr. Murali, could you explain about MPS and whether all individuals with MPS experience similar eye issues? Should they be particularly watchful for eye related problems?
Mucopolysaccharidosis (MPS) is a metabolic storage disorder caused by abnormalities in lysosomal enzymes that break down glycosaminoglycans (GAGs) which are important building blocks in the body. There are currently nine known types of MPS.
In the case of Kalpesh’s son, MPS VI was diagnosed. Except for type II, most types of MPS involve the eyes. However, in his case, he did not have glaucoma or optic nerve issues. It was the corneal clouding due to the deposition of GAGs, which impaired his vision. Lamellar corneal transplantation was performed, which improved his vision and allowed him to engage in his routine activities. MPS is a lifelong condition with potential for ophthalmic and systemic complications. The family was informed and is prepared to manage any issues that may occur.
Dr. Murali, is there a typical age when vision issues are seen in MPS patients?
Generally, early signs of MPS related vision issues can appear between three to four months of age and become more noticeable between six months to one year. Facial features change and corneal haziness may be observed during this time. If MPS is diagnosed early, especially within the first six months, effective treatment options like gene therapy, hematopoietic stem cell transplantation and enzyme replacement therapy are available. Enzyme replacement therapy is most beneficial if started before the child is two years old. Stem cell transplantation is most effective if initiated within six months of diagnosis. Early interventions can lead to better outcomes. Hence, early recognition of MPS is crucial for effective management and potential cures.
Nirav, could you describe your daughter Nidhi’s early symptoms and your journey to the diagnosis?
My daughter Nidhi, is 17 years old and suffers from nephrotic syndrome, proximal renal tubular acidosis and hypothyroidism. We consulted many doctors and underwent numerous tests, but could not get the accurate diagnosis. After a challenging seven year journey, she was finally diagnosed with Fanconi syndrome with nephrotic cystinosis during our visits to AIIMS. From there, we were referred to Dr. Murali at LV Prasad Eye Institute.
We noticed symptoms such as frequent urination (polyuria), vomiting and growth retardation. My daughter also had eye issues such as shrinking her eyes and difficulty seeing clearly when she was 3 years old. A local paediatrician suggested that the frequent urination was normal and gave medication for vomiting. Ophthalmologists told us the eye shrinking was normal. Another doctor prescribed a week of TB treatment due to her weak body. I kept visiting various doctors for opinions as I was not satisfied with the diagnosis. Eventually, a paediatrician suspected the renal issue and diabetes insipidus. We also consulted a genetic specialist, but it was not helpful. Later a nephrologist who diagnosed her with Fanconi syndrome which was confirmed later at AIIMS with nephrotic cystinosis.
Dr. Murali, can you comment on the diagnosis journey of Nidhi and why eye issues went unnoticed by some specialists?
Diagnosing any rare disease is challenging. These conditions are often autosomal recessive and involve defects in specific genes necessary for amino acid metabolism. In Nidhi’s case cysteine metabolism is affected due to a defect in CTN gene. Cysteine accumulation can cause symptoms such as polyuria, growth retardation and eye issues.
There are approximately 9,90,000 genetic conditions making it difficult to pinpoint the issue, which can lead to misdiagnosis. Awareness and training are required to improve the diagnosis of rare diseases. Although there may not be a complete cure, managing the symptoms effectively can improve the quality of life. Comprehensive diagnostic tools and genetic testing can also help, though cost and availability can be issues in India.
Nirav, how do you share responsibilities as a caregiver? What was her reaction when you told her about her condition?
Nidhi’s mother and younger brother are very supportive. Her brother cares for her like an elder sibling whenever we go out. Her mother has also sacrificed a lot to manage Nidhi’s condition and take care of her. We need special eye drops for her eye issues. I tried getting them prepared locally, being in the pharmaceutical field. But it did not work. We get those drops from France and USA with the help of our friends. Medicines for genetic diseases are limited in India, but they could be made here with research and development by utilising pharmacy students.
She was 12 years old when I informed her about her eye issues, she learned to manage it.
Seeing my daughter play and her smile motivates us to work hard. We have to accept the situation as it is and do our best for her health.
Kalpesh, how do you manage your son’s condition? What was his reaction when you told him about it?
Unfortunately, everyone has lost hope except me. I am doing my best to take care of him. I started by telling him about his condition, explaining that he won’t be able to play or do physical activities like his other friends. I encouraged him to google the disease and ask me if he has any query. It has been a roller coaster journey to see our child in this condition, but he is also trying to handle the situation. His school teachers help by tolerating his mischief and asking someone to carry his bag. He has no friends, and nobody wants to accompany him. While everyone else is playing, he has to sit in a corner, which has affected his mental health. I always try to stay strong in front of him though it is quite difficult for me many times. I need everything to be perfect, but I am adjusting for my child. It makes me sad to see this happening to my child. ‘I want you to live before you leave’ is what I told him. Whatever he asks for, I try to get him. He loves travelling and food, so I do my best to provide him with what he loves.
Dr. Murali, can you discuss the advancements in treatment options for rare diseases?
There are indeed promising treatment options available for rare diseases if detected early. Currently only 5% of rare conditions are treatable with existing therapies. Timely diagnosis can help avoid further complications. For condition like MPS, it can be managed effectively if detected early. Treatments such as hematopoietic stem cell transplantation within the first six month or enzyme replacement therapy within the first two years can significantly improve outcomes. In rare ophthalmic conditions like Retinitis pigmentosa or Leber Congenital Amaurosis (LCA) gene therapy can help a lot. For LCA, luxturna treatment is available in the US, can replace defective copies of the RPE65 gene, delaying the progression of vision loss. Though the treatment is quite expensive, it can preserve vision and delay blindness which can occur after 20s or 30s. Additionally, there are promising clinical trials and research going on cone- rode dystrophy. These treatments are not widely available but it is considered as a step forward in managing rare eye diseases. Advocacy at the government level is required to ensure the availability of these therapies here. We are hopeful that more effective treatments will be available for patients and families.
Any advice to parents on preventing the recurrence of a genetic disease in future children.
As part of our approach at LVPEI, we emphasize more on genetic counselling. When both parents are carriers of a genetic condition, there is 25% risk that their next child could inherit the same disease. We offer family counselling to help parents make informed personal decisions and discuss the risks whether they want to take 25% risk. If parents are willing to take risk, we offer extensive prenatal counselling to ensure that next baby is free from the disease. This approach is effectively implemented by many centres, which empowers families to make decisions. Ultimately the decision lies with family, as genetic counselling can provide guidance and clarity, supported by medical advice and resources.
Indian Health Outcomes, Public Health and Economics Research Centre (IHOPE) is an exciting collaborative and interdisciplinary research centre that has been set up with a research grant from the Wellcome Trust/ DBT India Alliance to L V Prasad Eye Institute, Hyderabad. It brings together clinical researchers, health economists and public health researchers on a single platform to answer important questions in eye health through big data analysis. Please visit https://www.ihope2020.org/ for more information
