Pompe disease is a rare disease continuum with variable rates of disease progression and different ages of onset. First symptoms can occur at any age from birth to late adulthood. Earlier onset compared to later onset is usually associated with faster progression and greater disease severity. At all ages, skeletal muscle weakness characterizes the disease, causing mobility problems and affecting the respiratory system.
The most severely affected infants usually present within the first 3 months after birth. They have characteristic heart (cardiac) problems (dysfunction due to heart enlargement) in addition to generalized skeletal muscle weakness and a life expectancy of less than 2 years, if untreated (classic infantile Pompe disease). Less severe forms of Pompe disease with onset during childhood, adolescence, or adulthood, rarely manifest cardiac problems, but gradually lead to walking disability and reduced respiratory function.
The scientific literature has different ways of subdividing the clinical spectrum of Pompe disease. Some articles describe ‘classic infantile’, ‘childhood’ and ‘adult’ Pompe disease while others discuss ‘infantile-onset’ (IOPD) and ‘late-onset’ (LOPD) disease.
Pompe disease is a rare, multisystemic, hereditary disease, which is caused by ‘pathogenic variations’ (abnormalities / mutations) in the ‘GAA gene’.
The GAA gene contains the genetic information for the production and function of a protein called ‘acid alpha-glucosidase’ (GAA). Shortage of this protein hampers the degradation of a complex sugar named ‘glycogen’ into a simple sugar named ‘glucose’. Therefore, glycogen starts to accumulate in all kinds of tissues, but primarily in skeletal muscle, smooth muscle and cardiac muscle, where it causes damage to tissue structure and function. ‘Enzyme replacement therapy’ (ERT), the only treatment presently available, aims to replenishing the shortage of GAA by intravenous administration of industrially made ‘rhGAA’ (recombinant human GAA).
Pompe disease is inherited in an autosomal recessive genetic pattern, which implies that healthy parents can have affected children.
Iris inherited two mutated GAA genes from us. Both Alex and I are carriers for Pompe Disease and had no clue of this until after her diagnosis and confirming this through blood tests.
Iris had hypertrophic cardiomyopathy (now resolved with the help of her weekly infusions) and is closely followed by the cardiology team at sick kids. Her heart muscle is now the size it should be. She does not struggle with any liver complications, breathing, or feeding, although these areas are all being monitored as there is often complications with these areas in Infantile Onset Pompe Disease.
Iris does have low tone and damage from early months where she was not receiving treatment. We have been told this muscle damage will not be repaired by ERT, however her current treatment (Enzyme replacement therapy) is preventing further muscle breakdown.
Her first infusion was at Sick Kids on December 22, 2021. Although it was a long 12 hour day, Iris’ cheery smiles, and knowing we would be home for her first Christmas made the time pass by. Every week for the next 24 weeks we travelled to Sick Kids. We always wanted to be a travelling family, but never did we imagine it would be weekly trips to Toronto Sick Kids. We would take a day to travel down, day for infusion, and then travel home the following day. Somehow we got use to the weekly trips, and were that much more thankful when returning home. It was only after her 17th infusion that she had surgery for a Port which is placed in her upper right chest. This was a blessing for Iris and the medical team as it meant less challenges to begin her infusions. In June 2022 we were able to begin her infusions in Sudbury at HSN, where she continues to go weekly. As of her two year diagnosis anniversary she had 99 infusions.
We are so lucky that there is treatment (ERT) for Pompe Disease and that it is funded. Pompe disease is progressive, and she requires weekly ERT UNTIL medicine advances or a cure is implemented.
Firstly, Enzyme replacement therapy is not a cure for Pompe disease, however it can slow the disease's progression.
The most common method of ERT is through IV infusions, in which the replacement enzyme is administered directly into the bloodstream through a controlled drip of fluids. (Iris has been receiving her infusion through her PORT since infusion #19 -she had PORT surgery placement on May 17th, at Sick Kids).
Replacement enzymes for ERT are derived from human, animal, and plant cells that are then genetically modified and processed before being given to the patient. By receiving these enzyme replacements, the body is able to successfully perform the functions inhibited by the deficiency. The effectiveness of ERT varies from person to person.
Infusions of the deficient enzyme (GAA) or a genetically modified replica are administered into the body, allowing it to successfully turn glycogen into glucose (glycogenolysis). This process is what allows the body to properly use sugars and create energy at the cellular level. Like other lysosomal storage diseases, ERT treatments for Pompe disease must be given regularly. Although years ago it was suggested that patients with Infantile Onset Pompe Disease do infusions every two weeks, recently research and literature suggests weekly infusions (in which Iris receives them weekly).
While in many cases ERT is the only effective treatment for a given lysosomal storage disorder, there are also some limitations and side effects to consider, such as:
· High cost of treatment. ERT treatments are expensive, with yearly costs in the hundreds of thousands of dollars. For most people this requires hefty assistance from insurance. Iris medication is covered through OHIP and the drug company also provides some compassion care funds to cover additional prescriptions.
· Immunological response against the infused enzyme.ERT can trigger immune responses based on how the body reacts to the infused enzyme. These effects will vary from person to person.
· Development of resistance to enzymes. The effectiveness of some ERTs can decrease over time if the body develops a resistance to the replacement enzymes.
· Not a cure. Lifelong treatments are necessary with any ERT, sometimes even when adverse effects occur. While ERT can replace deficient enzymes, it does not produce in the body an ability to make them, so treatments must be given for the entire duration of a patient’s life in order to mitigate the effects of having a lysosomal storage disorder.
· Uneven biodistribution. This means that the replacement enzyme is not distributed the same across the entire body and its organs. Therefore, the effectiveness of the therapy may be limited in certain areas of the body, and some symptoms of the LSDs may persist