Expert & MLDA Share Insight into a Rare Disease Called Pompe Disease

WORDS MALAYSIA LYSOSOMAL DISEASES ASSOCIATION (MLDA)

FEATURED EXPERT
DR NGU LOCK HOCK
Consultant Clinical Geneticist and Paediatrician
Hospital Kuala Lumpur

While rare diseases may seem distant to many, they are more prevalent than commonly perceived. Dr Ngu Lock Hock highlights that thousands of rare diseases collectively affect around 300 million individuals worldwide.

Among these is Pompe disease, a genetic disorder characterized by a deficiency in the enzyme acid alpha-glucosidase (GAA), leading to muscle weakness due to glycogen build-up. In Malaysia, there are only 17 diagnosed cases of Pompe disease.

What happens inside our cells when we have Pompe disease. Click on the image for a larger, clearer version.

SYMPTOMS OF POMPE DISEASE
The following symptoms often manifest when one is a baby or young child.
  • Severe muscle weakness.
  • Breathing difficulties.
  • Swallowing issues.
  • Floppy baby syndrome: babies with weak muscle development that impairs their ability to make normal movements.
  • Older children experience difficulties in walking and experiences frequent falls.

Identifying these symptoms early is paramount, as prompt diagnosis and intervention can significantly impact disease progression.

Parents who suspect Pompe disease in their child should seek consultation with clinical geneticists, paediatricians, and neurologists.

Clinical geneticists in particular currently are available only in major public hospitals across Malaysia such as:

  • Kuala Lumpur Hospital (HKL)
  • University Malaya Medical Centre (UMMC)
  • Universiti Sains Malaysia Hospital (USM)
  • University Kebangsaan Malaysia Medical Centre (UKMMC)
  • Penang General Hospital (HPP)
DIAGNOSING POMPE DISEASE

Confirming a diagnosis of Pompe disease relies on enzymatic, genetic and genomic testing.

Dried blood spot (DBS) testing can be a convenient first step in diagnosing the disease. This minimally invasive test collects a small blood sample, which is then analyzed to measure GAA enzyme activity levels, providing an initial indication of Pompe disease.

Newborn screening programs are also instrumental in detecting Pompe disease and other lysosomal storage disorders early on. By including Pompe disease in newborn screening panels, healthcare providers can identify affected infants before symptoms appear, enabling timely intervention and improving long-term outcomes.

However, the rarity of Pompe disease poses a hurdle to timely diagnosis. With only a handful of rare disease specialists in Malaysia, early intervention remains a considerable challenge. Many patients end up seeing different doctors and specialists, sometimes for years, without being correctly diagnosed.

Hence, Dr Ngu emphasizes the need for heightened awareness among healthcare professionals, as symptoms may be mistaken for other conditions.

THE FINANCIAL BURDEN OF POMPE DISEASE

“Enzyme replacement therapy (ERT), the primary treatment for Pompe disease, comes at a substantial cost, up to RM500,000 per year. This burden is particularly significant considering a newly approved ERT offers a more effective treatment option, providing relief from the symptoms of Pompe Disease by improving muscle strength, lung function and walking distance,” says Dr Ngu.

Additionally, there are the associated costs of supportive therapies as part of the holistic management of the disease, including respiratory support for patients with respiratory failure, physiotherapy, rehabilitation, speech therapy, pain management, dialysis, and more.

MAKING A DIFFERENCE, FOR THE FUTURE

Despite the challenges, there are glimpses of resilience and determination in Pompe disease patients.

Through MLDA, patients and their families find practical and emotional support, fostering a sense of community in the face of adversity.

In the meantime, the Ministry of Health is developing a rare disease policy that includes access to the latest treatment and sustainable funding. Many are hopeful that this will include measures to help with earlier diagnosis, such as improved training for front-liners to recognize symptoms of rare disease and expanded screening tests for newborns.

For more about the Malaysia Lysosomal Disease Association (MLDA), visit their website and Facebook (links open in a new tab).

References:

  1. Shafie, A. A., Supian, A., Ahmad Hassali, M. A., Ngu, L. H., Thong, M. K., Ayob, H., & Chaiyakunapruk, N. (2020). Rare disease in Malaysia: Challenges and solutions. PloS one, 15(4), e0230850. https://doi.org/10.1371/journal.pone.0230850
  2. Kishnani, P. S., Steiner, R. D., Bali, D., Berger, K., Byrne, B. J., Case, L. E., Crowley, J. F., Downs, S., Howell, R. R., Kravitz, R. M., Mackey, J., Marsden, D., Martins, A. M., Millington, D. S., Nicolino, M., O’Grady, G., Patterson, M. C., Rapoport, D. M., Slonim, A., Spencer, C. T., … Watson, M. S. (2006). Pompe disease diagnosis and management guideline. Genetics in medicine : official journal of the American College of Medical Genetics, 8(5), 267–288. https://doi.org/10.1097/01.gim.0000218152.87434.f3

A Neurosurgeon Discusses Trigeminal Neuralgia, the ‘Suicide Disease’

WORDS LIM TECK CHOON

FEATURED EXPERT
DR SYED ABDULLAH AL-HADDAD
Consultant Neurosurgeon
Sunway Medical Centre

Trigeminal neuralgia, also known as the ‘suicide disease’ or tic douloureux, is a rare and agonizing condition. While it is considered a rare disease due to its low occurrence among us, it has gained notoriety due to celebrities such as George Clooney and Salma Hayek revealing that they suffer from it.

It is more prevalent among women as well as people over the age of 50.

FACTS ABOUT TRIGERMINAL NEURALGIA
Causes a sudden, intense, stabbing, or electric shock-lain pain in the jaw or face

People with this disease can experience brief bouts of intense pain while carrying out daily activities that involve facial movements, such as chewing, talking, smiling, and more.

Dr Syed Abdullah Al-Haddad reveals that such painful episode can last from a few seconds to several minutes each time.

The pain is recurrent—one could experience a few to even a few hundred such attacks in a day!

He adds: “The intense, electric shock-like one-sided facial pain characteristic of this condition often leads to misinterpretation and misdiagnosis. Patients endure years of debilitating pain with one patient describing it as worse than labour pain.”

Commonly affects one side of the face

These bouts of pain commonly affect only one side of the face (the right side is more common). It is possible for both sides of the face to be affected, but such incidences are rare in an already rare disease.

It’s due to the disruption of the function of the trigeminal nerve

The trigeminal nerve transmits touch and pain sensations from our face and head to our brain.

There are 3 branches in the trigeminal nerve:

  • The ophthalmic branch transmits nerve impulses to the top portion of our face, including our forehead.
  • The maxillary branch transmits nerve impulses to the middle region of the face, including our cheeks, nostrils and upper lip.
  • The mandibular branch transmits nerve impulses to the lower portion of our face, including the lower lip and jaw area.
Causes of trigeminal neuralgia

One of the more common causes is a blood vessel causing pressure on the trigeminal nerve.

Another common possible cause is multiple sclerosis, which causes the myelin sheath, the coating of nerve cells, to break down and put the person with multiple sclerosis at risk of developing trigeminal neuralgia.

Other possible causes include the presence of a tumour or lesion that compresses the nerves and damage to the trigeminal nerve due to surgery, stroke, or injury.

However, it is also possible for some cases of trigeminal neuralgia to have no specific identifiable cause.

It is often misdiagnosed

Due to how it is often misdiagnosed, trigeminal neuralgia can cause those affected to live with the pain for a long time. Dr Syed Abdullah Al-Haddad shares that one of his patients had one whole side of his teeth taken out due to his condition being misdiagnosed as dental pain.

Leaves a profound impact on the lives of those affected by this disease

The disease can make it difficult for those affected to perform daily activities like eating and talking as well as affect their mental health and relationships with their loved ones.

Dr Syed Abdullah Al-Haddad adds: “As they endure the intense pain, some patients decide to stop talking or even living a normal life. The symptoms can also interfere with their ability to work, impact relationships as some believe that sufferers are ‘mad’ or exaggerating their pain and lead to depression and sleep problems.”

DIAGNOSING THE DISEASE

According to Syed Abdullah Al-Haddad, the biggest challenge here is getting an accurate diagnosis.

Frequently, the condition is misdiagnosed as dental problems or issues related to the ear, nose, and throat first.

This is why it is crucial for doctors to listen to their patient’s symptoms and understand the characteristic features of the pain. The pain often described by patients is crucial and can be a sign of the disease.

Trigeminal neuralgia is diagnosed through a combination of patient-reported symptoms as well as a thorough physical examination and a magnetic resonance imaging (MRI) scan to rule out other potential causes such as multiple sclerosis or tumours.

TREATMENT

Treatment options include medications to block pain signals and surgical methods such as stereotactic radiosurgery.

The latter is a non-invasive procedure that delivers focused radiation to the trigeminal nerve root, reducing pain signals with a shorter recovery time and surgery to relieve pressure on the trigeminal nerve.

BE AWARE OF THIS DISEASE

Dr Syed Abdullah Al-Haddad tells us: “With trigeminal neuralgia often being misdiagnosed, it is important for rare diseases such as this one to not only be in the minds of neurologists but all healthcare professionals from general physicians, dental, ENT surgeons to the public alike so these patients can get the help they need and do not need to suffer any longer in silence.”

IJN and Pfizer Shines the Spotlight on a Rare but Deadly Heart Disease

WORDS LIM TECK CHOON

FEATURED EXPERT
DATO’ DR AZMEE MOHD GHAZI
Consultant Cardiologist & Clinical Director
Heart Failure and Heart Transplant
National Heart Institute (IJN)

On May 8 this year, the National Heart Institute (IJN) and Pfizer Malaysia came together to promote greater awareness of transthyretin amyloid cardiomyopathy (often shortened to ATTR-CM), a rare, life-threatening disease.

An overview of ATTR-CM. Click on the image for a larger, clearer version. Image courtesy of Pfizer and IJN.
WHAT IS TRANSTHYRETIN AMYLOID CARDIOMYOPATHY?
  • ATTR-CM is caused by unstable transthyretin proteins that misfold and aggregate into amyloid fibrils that build up in the heart and other parts of the body.
  • This build-up of amyloid then causes the heart muscle to stiffen over time, eventually leading to heart failure.
  • Treatment is available, but detection of this disease tends to occur only at advanced stages due to lack of awareness of the disease.

“Diagnosis of ATTR-CM was often delayed or underdiagnosed due to the lack of optimal diagnostic modalities,” says Dato’ Dr Azmee Mohd Ghazi, a consultant cardiologist.

WHAT HAPPENS WHEN ONE HAS ATTR-CM?

According to Dato’ Dr Azmee:

  • ATTR-CM can lead to progressive heart failure, arrhythmias, and conduction system diseases (diseases that affect the ability of the heart to transmit electrical signals that keep the heart beating), all of which can result in sudden cardiac death due to fatal arrhythmias or complete heart block.
  • Once diagnosed, the average life expectancy for people with ATTR-CM is about 2 to 3.5 years, depending on the sub-type, if left untreated.

“Given how similar ATTR-CM symptoms are to other diseases’ symptoms, getting an accurate diagnosis from the onset can be an uphill battle,” Dato’ Dr Azmee. “However, medical advancements ensure that there are multiple channels to diagnose ATTR-CM, including nuclear scintigraphy and echocardiography.”

He adds that studies have also found that a multidisciplinary approach, involving multiple health departments, works best to facilitate earlier diagnosis and management of the disease.

SYMPTOMS TO WATCH OUT FOR
Symptoms of ATTR-CM, courtesy of Pfizer and IJN. Click on the image for a larger, clearer version.

Symptoms of ATTR-CM are not specific, and they are often similar to symptoms of other conditions such as an abnormal heart rhythm, muscle weakness, and bladder dysfunction.

Nonetheless, one should be alert for these symptoms and consult a doctor for confirmation, as early detection will improve the odds for a better treatment outcome.