Lysosomal Storage Diseases - the group of rare diseases that affects MalaysiansSYAHIRAH MOKHTAZAR NURUL ATIKAH SARJI
The thing with rare diseases is that they are just that - rare. Unfortunately, this leads to a host of other problems like lack of awareness, treatment inequality, and scarcity of resources, to name some.
According to the National Institute of Health (US), there are approximately 6,000 to 8,000 rare diseases worldwide.
Better management of rare diseases is crucially needed and if society as a whole, encompassing healthcare providers, governments, and politicians can work together, we can shape a future where nobody gets left behind.
In Malaysia, Lysosomal Storage Diseases (LSD) is something that needs better understanding and awareness.
Hospital Kuala Lumpur Genetics and Metabolic head of department Dr Ngu Lock Hock said Lysosomal Storage Diseases (LSDs) are a group of rare genetic diseases due to the defective functioning of lysosomes, an organelle in our cells that functions as a recycling centre.
“Lysosomes contain many enzymes that are able to break down cellular waste products into simple compounds, which are then being reused as new cell-building materials in our cells.
“In LSDs, the enzymes of the lysosomes do not work properly. As a result, waste materials build up in the lysosomes over time and cause damage to the organs of the body. More than 50 LSDs have been described so far with varying ages of onset, from childhood to adulthood,” he said.
So far, it is estimated that there are only about 300 cases being diagnosed in Malaysia. The more common LSDs in Malaysia are Pompe disease, Mucopolysaccharidoses (MPS) which have many subtypes such as MPS Type I, Type II, and Gaucher disease.
An LSD patient will typically experience an accumulation of waste materials in their organs, which will then lead to conditions like enlarged liver, and enlarged spleen. This will cause a difference in clinical features such as a bulging forehead, flat nose, and large lips.
However, these clinical features may differ among different LSDs.
“Muscle weakness and wasting are prominent in Pompe disease. Bones and joint deformities are key features in MPS. Bleeding tendency and anemia occur frequently in Gaucher disease. Many LSDs also cause developmental delay and intellectual disability,” he said.
Malaysian Lysosomal Disease Association president Ir. Lee Yee Seng said some lysosomal diseases can be severe and life-threatening, leading to reduced life expectancy.
“However, advancements in treatment options and supportive care have improved outcomes for many patients, allowing them to live longer and have a better quality of life.”
He added that the lack of awareness surrounding lysosomal diseases can be attributed to several factors such as rarity, as the low prevalence of these diseases often results in limited knowledge among healthcare professionals, the general public, and even some medical schools. This lack of familiarity contributes to the overall lack of awareness.
Another reason is that lysosomal diseases can present a wide range of symptoms that vary, depending on the specific disorder and affected organs.
“Many symptoms, such as fatigue, organ enlargement, bone abnormalities, and neurological problems, are not specific to lysosomal diseases and can be attributed to other more common conditions.
“This can lead to misdiagnosis or delayed diagnosis, further impeding awareness and recognition of these disorders,” he said,
Other reasons would include a lack of treatment options, and emotional and financial burdens as treatment is costly.
The treatments for LSDs include bone marrow transplant (BMT) and enzyme replacement therapy (ERT) among others.
“BMT is the treatment of choice for MPS Type I but it needs to be performed before the patient turns two and must have a matched donor.
“ERT is a life-changing treatment and is currently available for about 10 types of LSDs including Pompe disease, Gaucher disease, and a few types of MPS,” said Dr Ngu.
When a patient gets treated with ERT, this is what typically happens - an enzyme is manufactured using genetic engineering technology and given to patients by intravenous infusion to replace the missing lysosomal enzyme. ERT is done weekly or bi-weekly, for life.
ERT is extremely expensive and can cost up to RM500,000 or RM1.5 million per year per patient, depending on their body weight.
Of course, getting treated early promotes a better outcome for the patient.
Other treatments for LSDs include Substrate Reduction Therapy (SRT) which uses medications to inhibit the synthesis of the substances or to enhance their breakdown.
The Chaperone Therapy is a treatment where chaperone molecules can stabilise and assist in the proper folding of deficient enzymes, enabling them to function more effectively. Hematopoietic Stem Cell Transplantation (HSCT) is used in certain lysosomal diseases to replace the patient's bone marrow with healthy donor cells and supportive care such as physical therapy, occupational therapy, and medications, may be employed to manage specific symptoms and improve the overall quality of life
But beyond ERT, patients are also required to see doctors and healthcare professionals from multiple disciplines to monitor the function of various organs and to seek supportive care including physiotherapy, occupational therapy, pain therapy, and surgery for various complications.
MALAYSIAN LYSOSOMAL DISEASES ASSOCIATION (MLDA) AND ITS MISSION "RIDE WITH HOPE" TO RAISE AWARENESS ON LSDs
For patients of LSDs and their caregivers, support in various forms is crucial to soldier on.
Thankfully, there are kind-hearted individuals under the Malaysian Lysosomal Diseases Association (MLDA) non-profit organisation, who are dedicated to creating awareness about lysosomal diseases and providing support to patients and families affected by these rare disorders.
“The MLDA aims to improve the lives of individuals affected by lysosomal diseases through various initiatives.
“One of their notable initiatives is Ride With Hope, which is an annual charity cycling event. The event aims to raise funds for the MLDA's activities and to create awareness about lysosomal diseases among the general public,” said Lee.
Ride With Hope brings together participants from different backgrounds, including cycling enthusiasts, patients, families, and supporters.
“It provides an opportunity for people to come together, participate in physical activity, and contribute to a noble cause.
“The funds raised through this event are utilised by the MLDA to support affected individuals and their families, facilitate patient employment, enhance medical care, and conduct educational programmes,” he said.
Through this initiative, Ride With Hope has created a sense of community and support among individuals affected by lysosomal diseases. It provides an opportunity for participants to connect, share experiences, and find solace in knowing that they are not alone in their journey.
Lee said the event provides a platform for the MLDA to engage with policymakers, healthcare professionals, and other stakeholders.
“By highlighting the challenges faced by lysosomal disease patients and their families, the MLDA can advocate for improved access to treatments, diagnostic tools, and supportive services.
“Ride With Hope has been instrumental in raising awareness, generating funds, building a supportive community, and advocating for lysosomal diseases in Malaysia. It has significantly contributed to improving the lives of individuals affected by these rare disorders,” said Lee.