Rethinking rare diseases: The silent challenge of hunter syndrome (MPS II)

By Dr. Priyanshu Mathur, State Nodal Officer for Rare Diseases, Rajasthan

Hunter Syndrome, or Mucopolysaccharidosis Type II (MPS II), is a tragic example of how genetic conditions can dramatically change the lives of affected individuals but remain largely invisible to society. MPS II is not only a medical diagnosis but a call to action in regard to increased awareness, early intervention, and, more importantly, equitable healthcare.

MPS II arises from a deficiency in the enzyme iduronate-2-sulfatase (IDS), which is required to break down the glycosaminoglycans (GAGs) in the body. In its absence, GAGs build up in cells, causing progressive destruction in multiple organ systems. It is X-linked and occurs mainly in males, but in rare cases, it can be observed in females due to skewed X-chromosome inactivation.

The symptoms are usually seen between 18 and 36 months of age, although there is a wide range of presentation, which is often classified in severe and attenuated forms. In the extreme type, common in two-thirds of patients, children develop progressive mental impairment, developmental regression, and behavioural disturbances, including hyperactivity or aggression. Physical signs can include coarse facial features, i.e., broad nose, a tongue and forehead that are enlarged, short stature, stiffness of joints, and skeletal deformities such as broad chest, or some abnormalities with the spine. There are frequent respiratory complications, such as obstruction of the upper airway, sleep apnea, and frequent infections as a result of narrowed airways and poor mucus clearance.

Prevalence of MPS II in India

In India, prevalence is estimated at 3.5–4.5 per 100,000 live births, based on analyses of global IDS gene variants, where India accounts for 5.8% of reported cases worldwide. This rarity makes it invisible in the health discourse of the population, but increases the urgency to raise awareness; rarity should not be taken as negligence. Progressive complexity implies that the life expectancy in extreme cases without treatment may be 10-15 years, which is mainly related to the respiratory or cardiac failure. In milder cases, they can live till they reach their 60s, but because of chronic pain and disability, the quality of life is reduced.

Drawing from prevalence data, India's large population translates these figures into a significant patient burden. As of 2023–2024, lysosomal storage disorder support groups report about 180 officially registered children with Hunter Syndrome in India. This is, however, most likely to be an underreport as most of the cases may remain undiagnosed, as access to genetic testing and awareness among primary care providers is limited in the country.

Availability of ERT in India

MPS II has no cure, and enzyme replacement therapy (ERT) is one of the foundations of the treatment, which is intended to provide the missing IDS enzyme and slow down the build-up of GAGs. With a route of administration in the form of weekly intravenous infusion, ERT, administered via weekly intravenous infusions, has shown to better physical symptoms, such as joint range, respiratory functions, and even organ size but the drug fails to penetrate the blood-brain barrier, which limits its effectiveness on cognitive impairment.

ERT is present in India, but is not evenly distributed because it is expensive and logistically difficult to access. Such approved therapies require multidisciplinary treatment, including paediatrics, pulmonologists, neurologists, and therapists. Organisations like the MPS Society and lysosomal storage disorder support groups advocate for subsidised access, yet many families face out-of-pocket expenses

that escalate with the child's weight. New interventions, including hematopoietic stem cell transplantation (HSCT) in the early severe cases, are promising to stop the development, including the neurological outcomes, but have risks and are restricted to specialised institutions.

Prenatal genetic counselling and carrier screening efforts are crucial in India, as the X-linked inheritance type does exist, and the empowerment of informed reproductive decision-making by the family members is essential.

Raising awareness: A collective effort

MPS II makes us reconsider the 'right to life' as not just survival, but rather as early diagnosis, accessible care, and comprehensive assistance. The families carry the invisible labour associated with the coordination of therapies, emotional fatigue, and advocacy of resources, which often occurs without adequate mental health integration. Knowledge is the antidote to stigma; genetic counselling substitutes guilt with awareness and understanding.

Policymakers, clinicians, and communities must focus on rare diseases. Introduce new-born screening, invest in research, and establish support groups. Early intervention can change someone's future; however, delay turns potential into a massive loss.

About the Author

Dr. Priyanshu Mathur is the Rajasthan State Nodal Officer for Rare Diseases. Dr. Mathur has done is MD in Pediatric Medicine, Fellowship in Metabolic Genetic Disorders & Newborn Screening (USA), Masters in Neurometabolism & Cell Biology for Clinicians (Spain) and Ph.D in Genetics (Honorary).