On A Sensitive ‘Hunter’ Trail

India accounts for 5.8% of all reported IDS gene (iduronate-2-sulfatase) variants worldwide, based on analysis of over 2,200 global cases collected up to 2024. Prevalence in India is estimated at 3.5–4.5 per 100,000 live births Approximately 180 children with Hunter Syndrome are officially registered across India (as of 2023–2024), according to Lyso-somal Storage Disorders support data.

Dr Neel Khatri, a Mumbai-based paediatric geneticist says, “We have to be honest with families. For the severe type, life expectancy is under 12 years if left untreated. But with therapy and supportive care, we can significantly improve quality of life.”

The Early Clues

Hunter Syndrome, also known as MPS II (Mucopoly-saccharidosis Type II), often slips under the radar at first. Parents might notice their toddler has a larger-than-usual head, unusually stiff joints, or delayed speech. Some kids have what doctors call “coarse facial features,” or extensive Mongolian spots—blue-grey skin patches often brushed off as harmless.

“Short stature, stiffness in joints, and intellectual delays are early red flags,” Dr. Hedda explains. “Sometimes, even seasoned paediatricians miss the signs.”

But once it’s suspected, the diagnosis is fairly straightforward: a skeletal survey, a urine test to check for specific sugars, and an enzyme assay that confirms the deficiency of the iduronate 2-sulfatase enzyme.

Breathing Gets Harder

For every parent it’s a heavy moment when their child is diagnosed with hunter syndrome. It’s far more damaging from the inside than it is from the out. Dr. Hedda says, “We have to be realistic. The life expectancy in mild cases may be up to 60 years, but in severe ones, it could be just 20–30 years. That’s why thorough counselling is crucial.” Multisystem evaluations follow — eyes, ears, heart, lungs, brain, bones — every part of the body needs to be assessed. The condition affects all of it.

“The sugar molecules that aren’t broken down accumulate everywhere — including the lungs and airways,” says

Dr T. Vivek, Interventional Pulmonologist at Renova Century Hospital.

This buildup can lead to repeated throat infections, difficulty breathing, sleep apnea, and in serious cases, tracheomalacia — a condition where the windpipe itself collapses during breathing. These kids get tired quickly, they struggle with mucus clearance, and infections are a constant concern. While standard lung function tests like spirometry are tough for younger kids, newer techniques like impulse oscillometry or sleep studies are helping doctors measure lung health more effectively. In cases of sleep apnea, CPAP machines — devices that deliver air pressure — are often prescribed and can be used safely at home. Surgery becomes complicated too. Dr. Vivek adds, “The airways are narrow, and the anatomy is tricky. Anesthesia can be risky, so surgeries need to be planned with extreme care.”

Mind Matters

The bigger picture here that arises is, what about the brain? “As the brain gets affected, the child may experience behavioural issues, speech delays, and even seizures,” says Dr Joy Mounica, Consultant Neuro-logist, Renova. Seizures can be subtle or sudden. Sometimes, they’re the first real sign that something is wrong. Unfortunately, while current treatments can ease some physical symptoms, the impact on the brain is harder to reverse.

MRI scans help track progression, often revealing enlarged ventricles, hydrocephalus, and white matter changes. “These findings are consistent with what we see clinically: the child slowly regressing,” explains Dr Mounica. Doctors use a range of cognitive tests — from IQ assessments to story memory and spatial skills — to understand how the disease is affecting each child’s brain. Tools like the Wechsler scale, Connors Test, and NEPSY-II help tailor therapies for attention, memory, and motor function.

What’s Possible, and What’s Not

The only approved treatment today is Enzyme Replacement Therapy (ERT) — a weekly infusion that helps break down the sugars accumulating in the body. But there’s a catch: it doesn’t cross the blood-brain barrier. ERT improves physical symptoms, but for brain symptoms, we need to go further. Dr. Anuja Rao, a paediatrician from Mumbai says, “Enzyme Replacement Therapy with idursulfase is life-changing—but also incredibly expensive. As the child grows, the dosage increases based on weight, which means the financial burden doubles every few years.”

That’s where intrathecal delivery (injecting the enzyme into the spinal fluid) and stem cell transplants come in. HSCT (Hematopoietic Stem Cell Transplant) is considered promising, especially when done before neurological symptoms appear. But it’s not without risks, and it comes at a high cost. Gene therapy, still in clinical stages, holds the most hope for the future. “It could change the entire landscape of treatment,” Dr Mounica says, “but we’re not there yet.”

Genetic Testing

Since Hunter Syndrome is inherited in an X-linked pattern, genetic testing is a must for families. Mothers may be carriers without knowing it. If there’s already one child with the condition, future pregnancies must be tested. Doctors recommend antenatal testing to screen for the disorder in utero — something many families are unaware of.

From pulmonologists to neurologists, physiotherapists to speech therapists — treatment is truly a team effort. Parents often become full-time caregivers, constantly monitoring oxygen levels, attending therapy sessions, and adjusting to the changing needs of their child.

Support groups, while limited in India, are beginning to emerge online. Families are increasingly finding strength in sharing their stories.

Hunter Syndrome

• Hunter Syndrome, also known as MPS II. (Mucopolysaccharidosis Type II)

• Parents might notice their toddler has a larger-than-usual head, unusually stiff joints, or delayed speech.

• Some kids may have “coarse facial features, intellectual delays or extensive Mongolian spots—blue-grey skin patches.