Overview and challenges
Gaucher disease (GD) is an inherited lysosomal storage disorder. There are 3 subtypes; Type 1 has no neurological involvement (and is treated with enzyme replacement therapy); Type 2 results in infant death; and Type 3 is a heterogenous disorder characterised by progressive neurological decline throughout childhood and adult life.
Clinical features of neurological GD (nGD) include specific saccadic eye movement defect, altered muscle tone, coordination impairment, tremor and late in disease; ataxia. Patients also have varying severity of bone disease, kyphosis, scoliosis, hearing impairment and other non-neurological features such as lung infiltration or cardiac disease.
Endeavours to find a therapy to modify nGDare limited by a lack of meaningful clinical outcome measures which are acceptable to patients. Disease severity in nGDmay be described by the modified Severity Scoring Tool (mSST) which, although useful, fails to account for the functional impact of disease on patients and only give a momentary account of function, overlooking disease fluctuations and the factors which provoke them.
Twenty-one patients were enrolled in the UK and participated for up to 12 months.
Clinical measures included a neurological examination, the mSST, 6 Minute Walk Test (6MWT) and GAITIRiteor Zeno Walkway gait analysis.
The Aparitomobile app was paired with a 3D accelerometer device worn on the wrist, which captured data in 30 minutes epochs. The paired app pushed out Patient Reported Outcomes (PROs) and Quality of Life (QoL) scales at pre-set intervals. Patients could also record visits to health care professionals, other ‘events’ e.g. falls, seizures etc. and they were encouraged to record sleep quality.
Five patients with Type 1 GD and 16 patients with nGDwere included.
Fifteen patients completed the 6MWT; the mean distance walked by nGDpatients was 391m and by Type 1 patients was 475.67m. There was no statistical correlation between disease severity on mSSTand 6MWT distance.
Wearable device data comprised 3 different variables (average daily maximum (ADM), average daily steps (ADS), and average daily steps per 30-minute epoch (ADE)). These were considerably higher in the GD1 group compared with the nGDgroup (ADM almost 3 times; ADS 2.5 times; ADE almost double). Seven out of the 9 nGDpatients reported bone pain as an event indicating that this is a significant disease feature across the cohort. The CHU9D showed a statistically significant difference between disease groups, nGDpatients reporting overall lower health-related quality of life. Perceived stress was also significantly higher in patients with nGDthan GD1 patients.
Wearable device data showed a much higher level of activity in GD1 compared with
Bone symptoms in nGDpatients has a greater functional impact on activity and quality of life than perhaps previously recognised.