Building care pathways for rare diseases: From diagnosis to lifelong management

In India, rare diseases are not so rare. It is estimated that around 70 million Indians live with one of more than 7,000 rare diseases, many of which are genetic in origin. 

A 22-year review from a major Indian genetics center found that of more than 7,000 referrals, about half had a confirmed rare disease, most commonly involving the blood, muscles, nervous system, or metabolism.

What makes rare diseases particularly challenging is that they often take years to diagnose. Many patients undergo a “diagnostic odyssey,” visiting multiple specialists and undergoing numerous tests before finding an answer, if at all. Early and accurate diagnosis is critical, not only for treatment but also for family planning, genetic counseling, and better long-term care.

That’s where genetic testing and integrated care pathways come in.

The role of genetic testing

About 80 per cent of all rare diseases are genetic, which means they are caused by changes in a person’s DNA. Advances in genetic testing now allow clinicians to look deeper into the genome than ever before, pinpointing the exact cause of disease. Several types of genetic tests are used nowadays to diagnose rare diseases:

• Chromosomal microarray analysis: This is one of the most powerful first-line tools for uncovering the genetic basis of rare diseases. It can detect tiny deletions or duplications of DNA known as copy number variations that are a frequent cause of rare diseases.
• Single-gene testing: Used when a doctor suspects a specific genetic condition based on symptoms and family history. For example, testing the GBA gene for Gaucher disease or the CFTR gene for cystic fibrosis.
  
• Gene panel testing: Examines multiple genes at once, often used when several conditions have similar symptoms. Panels are especially useful in disorders like epilepsy or muscular dystrophy, where many genes can be responsible.
  
• Whole exome sequencing (WES): Looks at all the protein-coding regions of the genome (about 1–2 per cent of our DNA). These regions are where most disease-causing mutations occur. WES has been shown to provide a diagnosis in many previously undiagnosed rare disease cases.
  
• Whole genome sequencing (WGS): Examines the entire genome, including non-coding regions. Although more expensive, WGS can detect complex or structural genetic changes that other tests might miss.

Together, these tools are transforming the way doctors diagnose and manage rare diseases in India and around the world.

Ending the diagnostic odyssey

One of the biggest advantages of early genetic testing is reducing the diagnostic odyssey, the long, frustrating journey families face before getting a diagnosis. In pediatric care, trio-based exome sequencing (testing the child and both parents) is one of the most successful strategies used to achieve diagnoses when a rare disease is suspected.

In India, early access to genetic testing can save families years of uncertainty and unnecessary medical costs. For instance, identifying an inherited metabolic disorder early can allow doctors to start enzyme replacement therapy or dietary management, dramatically improving outcomes. An inherited metabolic disorder is a genetic condition (usually rare) where the body can’t properly convert food into energy because of a missing or faulty enzyme. For example, phenylketonuria is an inherited metabolic disorder where the body can’t break down an amino acid called phenylalanine. If left untreated, phenylalanine builds up in the blood and can cause developmental delays; but with an early diagnosis and a special low-protein diet, people with this condition can lead healthy lives.

For families, knowing the exact cause also helps in using prenatal or preimplantation genetic testing to prevent recurrence in future pregnancies.

From diagnosis to management

Genetic testing can do more than provide a diagnosis. It could help shape lifelong management. 

For example, in certain neuromuscular diseases, knowing the specific gene involved can determine whether a patient is eligible for gene therapy or clinical trials. For rare diseases like spinal muscular atrophy (SMA), identifying a mutation in the SMN1 gene can determine whether a patient is eligible for gene therapy (such as onasemnogene abeparvovec) or other targeted treatments.

Similarly, in metabolic disorders such as phenylketonuria (mentioned before) or maple syrup urine disease, genetic testing helps pinpoint which enzyme is affected, allowing doctors to tailor dietary restrictions and monitor for specific complications. In some cases, knowing the exact gene variant can also help predict which patients might benefit from emerging enzyme replacement or cofactor therapies, turning genetic insight into a personalized care plan for life.

Importantly, identifying one patient with a genetic disorder often has implications for the entire family. Cascade testing, which means testing close relatives of the affected person can help identify others at risk before symptoms appear or aid in their reproductive planning.

However, a genetic diagnosis can have emotional, social, and medical implications for families. This is why genetic counseling is a critical part of the care pathway. Counselors help families understand test results, manage expectations, and make informed decisions about treatment, surveillance, and family planning.

In India, there is growing recognition of the need for more trained genetic counselors and integrated genomic services in both public and private healthcare. Efforts such as the National Policy for Rare Diseases (2021) and the Genome India Project are steps toward improving access to testing and creating national genomic databases that better represent India’s diverse population.

Looking ahead: The future of precision medicine

Building effective care pathways for rare diseases requires not just clinical expertise, but also collaboration and data sharing. When genetic data from patients are combined with clinical observations, they accelerate new gene discovery, improve variant interpretation, and support the development of targeted therapies.

Collaborative platforms like ClinVar, Orphanet, and Indian Genome Variation Consortium help clinicians and researchers worldwide share information about rare variants and disease mechanisms. This collective approach helps translate genomic insights into better diagnosis and care for patients everywhere.

The integration of genetic testing into clinical practice marks a turning point for rare disease care in India. With the cost of sequencing steadily falling, and government initiatives promoting early diagnosis, genomic medicine is becoming more accessible.

The vision ahead is clear—to move from delayed diagnosis to early intervention, from fragmented care to integrated lifelong management. 

As India continues to strengthen its genomic infrastructure, rare disease patients and families can look forward to a future where answers come faster, and care is more precise and personalized.