Today, Professor Elsa Shapiro and Dr. Christina Lampe presented “Cognitive Impairment in Patients with MPS II: From Disease Burden to Cognitive Testing” at Satellite Symposium, an event sponsored by Shire at WORLD Symposium. To read about yesterday’s talk on long-term outcomes for MPS IVA and VI patients, click here.
Dr. Shapiro started with an introduction to mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, which is a genetic lysosomal storage disorder that impacts organ systems across the body. About two thirds of MPS II patients have the neuronopathic form and experience cognitive decline. To read more about MPS II, click here.
The discussion addressed the different ways of measuring cognitive ability in patients with both the neuronopathic and non-neuronopathic forms. Cognition, which was defined to include problem solving, communication, literacy, numeracy, and motor activities, can be measured throughout an entire lifespan. A typically developing child will gain skills that they can use as building blocks to living an independent life, but both congenital and environmental factors can limit these building blocks– including MPS II.
Cognitive abilities are measured through different tests, some of which measure a patient’s ability against normative data, and others which use an age equivalency score. An age equivalency score identifies what age level a patient is operating on, and is useful when monitoring a degenerative disease.
Age is important in the context of neuronopathic MPS II, which follows a particular development vector: first, the child’s cognitive development increases, then it slows down, plateaus, and finally declines.
Cognitive development in the neuronopathic form of MPS II isn’t fully understood, but the decline generally occurs between the ages of 2-5, which is a looser range than other types of MPS. There is not a huge amount of natural history data, and since MRI abnormalities are present in both neuronopathic and non-neuronopathic forms, MRIs are not predictive early on.
Shapiro encouraged striving toward monitoring progress, short, focus batteries of testing, and finding recommendations for appropriate therapy and school interventions. She stressed the importance of finding a tester familiar with the disease, and discussed the Bayley Scale of Cognitive Development for younger patients, and the Vineland Adaptive Behavior Scale for patients of all ages, which accounts for daily living and socialization.
The tests do not measure quality of life or behavior, two important qualities that are difficult to quantify.
Shapiro discussed challenges in finding accurate testing, including inexperienced testers, motor difficulties, hearing loss, illness, behavior, and poor concentration.
These obstacles make it difficult to accurately test non-neuronopathic patients– although they don’t experience cognitive decline, they may have lower test scores for other reasons. They may acquire language later because of hearing loss, or perform a non-verbal timed test later, not because they didn’t understand the concept, but because they didn’t have the motor skills to complete it quickly. These patients can also suffer from poor attention skills because of compromised white matter, and educational gaps from missing school to address health concerns. Shapiro cautioned that cognitive assessments should be untimed if possible, and taken with a grain of salt if not.
Next, Dr. Christina Lampe discussed the burden of the disease on the patient and their family, both physical and psychological. In many patients with MPS II, cognitive decline may be misdiagnosed as ADHD or an autism spectrum disorder, which deprive the patient of effective care. The disorder may bring behavior and sleep difficulties, generally linked to the time that cognitive decline begins.
There is also heavy physical involvement, including cardiac and gastrointestinal problems, affected appearance, loss of vision and hearing, respiratory symptoms, joint problems, and frequent infections. These health complications means that both non-neuronopathic and neuronopathic patients often have to stay home from school, and are deprived of socialization and education.
The disorder also has a great impact on parents, who are more prone to experiencing depression and chronic illness. Parents face an emotional weight and financial cost. They must maintain a flexible schedule to deal with arising medical concerns or sleep disturbance, and this takes a toll. In turn, the parent’s mood affects the patient. Any childhood illness, but especially a severe one, has impacts on everyone around– siblings, friends, teachers, parents, and doctors.
The presenters shared various case studies. The first case followed a patient who experienced symptoms early on, was evaluated and treated. He had the non-neuronopathic form, although his non-verbal cognitive scores were low, which was attributed to motor skill dysfunction. He now has stable health, and is pursuing his passion of computer science.
Another patient discussed had a very different outcome– this patient also showed symptoms early on in life. He left school at 18, and is now working in a protected work environment for people with intellectual disabilities, a job he is unhappy with. However, he was never thoroughly evaluated for cognitive decline, so it is unclear if he truly has an intellectual disability, or if the other obstacles he faced, such as health challenges, missed school, hearing loss, and motor skill impairment– factors that could have been identified and addressed through evaluation– have limited his options, and prevented his school and doctors from fostering his strengths and addressing his weaknesses.
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