Passing On A Destructive Gene

Haliza Md Kasim’s eyes widened. Despite having gone through this before with her first son, Yusof, and despite the doctors explaining that this was a genetic disease affecting boys, inherited from their mother – somehow, she had hoped that her two-month-old Irfan would escape this fate.

She sat in the doctor’s spartan Kuala Lumpur Hospital (HKL) office, her post-partum body still aching. The fluorescent lights above her hummed softly as the genetics specialist continued, detailing the available treatments Irfan would have to undergo.

“We have options,” he said. “Since we discovered it early, we can begin enzyme therapy immediately. It should improve his chances.”

The disorder that Irfan had tested positive for was Mucopolysaccharidosis Type II (MPS II), also known as Hunter Syndrome, which is when the body lacks the enzyme to break down sugar molecules in the body and remove them. It is a recessive X-linked disease, which means mothers have a 50 per cent chance of passing it to their sons. It is rare and progressively debilitating, affecting the mind and body. There is no cure.

Yusof, who was 6, had it. He could barely move or talk. And now his baby brother had it too. 

Next to her, her husband, Mohd Adam Sapardi, sat still. From the corner of her eye, she saw him cast a worried glance at her.

She took big gulps of air. She did not cry. She rarely did. Tears, she had found, were largely useless. Nevertheless, her fingers trembled slightly as she clutched her purse like a lifeline.

“This is a genetic disease. We should discuss testing your daughters to see if they are carriers,” the doctor said.

She inhaled sharply. Her daughters.   

She could almost see her daughters in the same room, twenty years from now, listening to a geneticist speaking in the same soothing tones, with the same empathetic manner, delivering the same devastating news. They would go through what she had endured over the past six years.

She felt like crying then. 

 

Adam and Haliza’s third child and first boy, Mohammad Yusof Asyraf, was born in 2009. They already had two girls in 2005 and 2007. With the birth of Yusof, they were halfway to their perfect family. They wanted six children.

There were complications when Yusof was born. He had a seizure, which Haliza thought was due to her gestational diabetes. 

Yusof claimed a lot of the couple’s time. He was an easy baby to love, cheerful and affectionate. But he would catch colds almost every week, with a few healthy days in between. And he was unusually calm. Even a slammed door didn’t wake or startle him.

Six months later, Yusof was not reacting to loud noises at all. The hospital had tested him for deafness when he was born, as was the protocol, and there was nothing amiss then. He was also a bit slow to crawl or talk.

“Maybe he has GDD,” Adam suggested. Haliza shook her head. As teachers, they have both been trained on common disabilities among children, like GDD or Global Developmental Delay.

Was this how GDD manifested itself? She wasn’t sure. 

They decided to take Yusof to the doctor.

Answers came late. In 2010, the hospital was unable to perform genetic tests in-house, so they sent the blood sample to a lab in Australia. When the results finally arrived a year later, they revealed a disease the couple had never heard of before: Hunter Syndrome, a lysosomal disorder affecting 1 in 100,000 to 170,000 male births. It is so rare that, as of 2020, only 39 people in Malaysia were known to have the disease, according to a research paper by Shafie et al.

Depending on the severity, life expectancy ranges between 10 to 20 years.

“Why me?” Adam sighed to his friends.

By this point, Yusof's condition had progressively worsened. At almost two years old, his hearing was mostly gone. His features had started to coarsen, with an enlarged head and bushy eyebrows. His growth had slowed, and he could not crawl or talk. When he slept, his snores were loud enough to wake the dead, his father would jokingly tell people. Meanwhile, his parents were surviving on around two hours of sleep.

Adam's friends offered non-committal words of comfort. One of them gently reminded him, “This is fate.” He bowed his head, his faith restored.

Haliza and Adam found that most of their conversations and activity now revolved around Yusof. They would travel to HKL every Friday so he could get the enzyme he needed to prevent his symptoms from worsening and prolong his life. They interrogated Haliza’s relatives to see if anybody had the same disease or symptoms. Everyone said no, but there was a great-uncle who died as a baby. Maybe that was it.

They decided to hold off on having another baby. They told their daughters that their brother’s disease now had a name.

The girls, around 4 and 6, were apathetic. Everything was about Yusof, they thought.

Their resentment manifested in many ways. Aisyah, as the eldest, had started school. There, she found a reprieve from her home life, denying she had a special needs brother or even a brother sometimes. She refused to have her friends over. 

“I was embarrassed to have a special needs brother,” she remembers thinking.

Her younger sister chose to keep silent.

 

At 36, Haliza found out she was pregnant again. She felt hopeful but also scared. What if this one was like Yusof?

Given her medical history, the doctor asked if she wanted to take a test to determine whether the foetus had Hunter Syndrome. They couldn't wait for the usual ultrasound, typically performed between 18 and 20 weeks to reveal the baby’s gender, as it would be too late by then to consider a therapeutic abortion.

In Malaysia, abortion is allowed during the first trimester if continuing the pregnancy would pose significant risks to the mother’s physical or mental health or if the foetus is diagnosed with a condition incompatible with life, as determined by medical doctors.

“If it is a boy, you have a 50 per cent chance of passing it to him.But if you do the test, there is a small risk of miscarriage,” he said.

She shook her head. On the one hand, it would be good to know. On the other, she may lose the baby. She didn’t think the risk was worth it but she couldn’t give an answer.

“I’ll talk to my husband and discuss what we should do,” she finally said.

Adam agreed with her. “It’s okay. We carry on with the pregnancy. In the meantime, we pray.”

When Mohammad Irfan Zahran was born, it seemed all her prayers had come true. From the moment she held him in her arms, he seemed more alive, more present, his tiny hand gripping her finger with a sweet strength. 

They were heartsick when Irfan tested positive for Hunter Syndrome. But then, Irfan continued developing normally after going on his enzyme therapy. They began to hope.

The differences were stark. While Yusof was sickly, Irfan was active, playful, and responsive. Like Yusof, Irfan was a cheerful and affectionate baby, but unlike his older brother, Irfan walked, talked and played. He could call out Mak for his mother, Ayah for his father and Kakak for his sisters.

His favourite pastime was sweeping the floors. He was obsessed with fried bananas, which were sold near his babysitter’s home. 

Adam was ecstatic. He took his son everywhere, introducing him to everyone he met. “This is my son, Irfan,” he would exclaim proudly. People oohed and ahhed, and showered the baby with praise.

Irfan was almost four when his parents noticed something wrong. He had started choking when eating, due to his enlarged tongue, a symptom of Hunter Syndrome.

Then he turned four. One day, Haliza called him, but he did not respond. When she asked him if he heard her, his face was blank and confused. 

 “It’s as if everything about him had disappeared. Gone just like that," Haliza said. Irfan quickly deteriorated.

When Irfan “disappeared,” the girls did not feel the same devastation her parents felt. 

Despite Irfan being normal for the first few years, his sisters never warmed to him. They knew his diagnosis. Both avoided the boys.

Aisyah had started informally adopting her friends' or cousins' baby brothers. She loved playing and carrying them around. She would count the fingers on their chubby hands, make them laugh with games of peek-a-boo, and comfort them when they cried.

Adam reminded her she had real brothers at home.

 

Yusof passed away quietly in 2020 at the age of 11. At the time of his death, he was completely dependent on his parents, just like Irfan now.

Both Adam and Haliza are steeling themselves for the day they have to say goodbye to Irfan, who is four months shy of his 11th birthday.

Although the boy had started therapy earlier than his brother, his mental deterioration seems worse.

“The enzyme doesn’t pass through the blood-brain barrier,” said Dr Ngu Lock Hock, head of the genetics department at HKL.

He said the waste from the complex sugar had continued building up in Irfan’s brain, destroying it.

Other than saying goodbye, the time has come to test their daughters. They were too young before, but now Aisyah is 19 and the second girl, known as Angah, is 17. They had mentioned it to the girls several times, explaining how the disease is passed from mother to son and stressing the importance of knowing. They also reminded the girls to bring future suitors home to their parents first, so they could explain to the men about the disease and how it may affect them.

“Kalau susah sangat, tak nak kahwin lah! (If it’s too much trouble, I won’t get married!)” their second daughter exclaimed.

Haliza told her that she didn’t want that to be the girl’s only choice. But knowing is a double-edged sword as well.

“Walaupun pasangan terima, tak semestinya family dia accept (Even if their boyfriend accepts them, their family may not),” she told Bernama, while keeping a close watch on the dosage levels of Irfan’s enzyme drip. 

Other than to prevent her daughters from experiencing the same heartbreak, she also wanted to give them a head start on planning their finances. A positive result meant they would probably have to do costly procedures, such as pre-implantation genetic testing and IVF (In-Vitro Fertilisation) if they wanted healthy children. 

She said the girls will be tested once Aisyah, who is in Jordan doing her Bachelor’s degree, comes back in September.

Aisyah, 19, said in an email that she was scared of testing positive, saying, "It could be a hereditary disease."

However, she said the right man will be able to accept her, defective gene and all, adding that she regretted her earlier behaviour towards her brothers.

“For me, the illness my siblings are facing is not a burden; perhaps it is a blessing from Allah," she added.

 

Edited by Salbiah Said