Awareness of Pompe disease among HCPs key to early diagnosis

Early diagnosis of the rare Pompe disease is a considerable challenge due to lack of awareness among healthcare professionals (HCPs) and symptoms may be mistaken for other conditions, said Dr Ngu Lock Hock, a consultant clinical geneticist and pediatrician.

Pompe disease is a lysosomal disorder also known as glycogen storage disease type II or acid maltase deficiency. It is caused by a deficiency of acid alpha-glucosidase (GAA) enzyme because of mutations in the GAA gene. The GAA enzyme is involved in the breakdown of glycogen into glucose, so the deficiency results in severe skeletal muscle weakness as well as difficulties in breathing and swallowing. While infants have floppy baby syndrome, older children usually struggle to walk or frequently fall. [Pediatr Neonatol 2013;54(4):219-227] In Malaysia, only 17 patients have been diagnosed with Pompe disease. [PLoS One 2020;15(4):e0230850]

Identifying symptoms of Pompe disease early is paramount, as prompt diagnosis and intervention can significantly impact disease progression, said Ngu, who is also the clinical lead of inherited metabolic diseases at the Genetics Department of Hospital Kuala Lumpur (HKL). Parents who suspect their child may have Pompe disease should be referred to clinical geneticists, pediatricians, or neurologists. Clinical geneticists currently can be located only in major public hospitals across Malaysia such as HKL, University Malaya Medical Centre (UMMC), Universiti Sains Malaysia Hospital (USM), Universiti Kebangsaan Malaysia Medical Centre (UKMMC), and Penang General Hospital (HPP).

The diagnosis of Pompe disease is dependent on enzymatic, genetic, and genomic testing. These tests can confirm if GAA enzyme is deficient and pinpoint mutations in the GAA gene which then helps determine the most effective treatment course for patients. A simpler procedure to diagnose patients early is dried blood spot (DBS) testing, which can be a convenient first step. 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 (LSDs) 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.

Currently, timely diagnosis of Pompe disease is hampered by its rarity. Therefore, Ngu emphasized the need for increased awareness of Pompe disease among HCPs, as symptoms may mimic those of other conditions. Also, early intervention continues to be a considerable challenge since only a handful of rare disease specialists are based in Malaysia. Many patients may have to consult different doctors and specialists, sometimes for years, without being correctly diagnosed. Moreover, patients and their families must bear the financial burden of managing the condition.

“Enzyme replacement therapy (ERT) is the primary treatment for Pompe disease, [and] comes at a substantial cost, ranging from several thousand ringgit per month to RM500,000 per year,” said Ngu. ERT offers a more effective treatment option and provides relief from the symptoms of Pompe disease by improving muscle strength, lung function, and walking distance. However, the financial burden is particularly significant, said Ngu.

Further, supportive therapies add to the cost as part of the holistic management of the disease, including respiratory support for patients with respiratory compromise or failure, physiotherapy, rehabilitation, speech therapy, pain management, and dialysis, among others.

Despite the challenges, there are glimpses of resilience and determination in the journey of patients with Pompe disease. Through the Malaysia Lysosomal Diseases Association (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. [https://www.thestar.com.my/news/nation/2023/02/28/urgent-need-to-establish-national-rare-disease-policy-says-ras-adiba] 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. [PLoS One 2020;15(4):e0230850]

Collective action by all stakeholders is vital in tackling the challenges of rare diseases. Malaysians can make a difference by raising awareness on social media, volunteering with organizations like MLDA, and providing financial support. By standing together, they can illuminate the path for those battling Pompe disease and other rare conditions, and offer them hope, solidarity, and ultimately, a brighter future with earlier diagnosis, better health, and improved well-being.

Patients suspected to have a rare disease can be referred to a specialist for further evaluation and diagnosis. For further information about MLDA, go to www.mymlda.com.