Five-parameter evaluation of dysphagia: A novel prognostic scale for assessing neurological decline in Gaucher disease type 2

Abstract

Background-Gaucher disease type 2 (GD2) is defined by acute neurological decline, failure to thrive, and early demise. Currently, there is no clear standard for evaluating, staging, and counseling regarding neurological decline in GD2. Due to the high prevalence of progressive dysphagia secondary to acute neurological involvement, we aimed to identify key components of swallow function which could serve as markers of disease progression in GD2. Methods-A post-hoc analysis of modified barium swallow studies was performed. Six parameters of swallowing were scored in a retrospective chart review of eleven infants with GD2. Mixed effects regression, principal component analysis (PCA), and a transition analysis were used to evaluate swallow function and model disease progression. Results-All patients exhibited impaired swallow function. There was no association between any of the swallow parameters and age, indicating non-linear disease progression. PCA and transition analysis identified five parameters capturing multiple dimensions of swallowing which defined two distinct disease states. Conclusion-A five-parameter swallow evaluation was sufficient to identify distinct states of GD2 and model prospective outcomes. This multi-dimensional evaluation could be a useful efficacy parameter for future therapeutic trials in GD2 and other neurodegenerative disorders of infancy.

The D409H variant in GBA1: Challenges in predicting the Gaucher phenotype in the newborn screening era

“…In fact, involvement of the outer layer of the epidermis has been postulated to discriminate between type 2 and 3 GD (Chan et al, 2011), but this evaluation is not readily available. Early stridor or difficulty swallowing is indicative of GD2, and a thorough swallow evaluation by an experienced team can be quite helpful (Seehra et al, 2019). Patients with GD2 can develop a distinct facial phenotype and there is some evidence that facial recognition software may help to discern the diagnosis (Daykin, Fleischer, et al, 2021).…”

The definition of neuronopathic Gaucher disease

“… Onset of neurological deficits by age 6 months* (in GD3 they appear at a later age) 13 Supranuclear gaze palsy/convergent squint*. Rapid neurological deterioration over months in the first 2 years of life*. Severe stridor and apnoea at some point, frequently necessitating tracheostomy by age 2 years*. Feeding difficulties due to abnormal swallowing often requiring tube feedings 14 Development of spasticity, opisthotonus and/or progressive myoclonic epilepsy by age 2 years. Failure to achieve independent gait (GD3 always achieve independent gait). Death by age 4 years except when extreme life support measures are applied. Patients with neurological symptoms that straddle GD2 and GD3 exist 2 …”

Two cases of neuronopathic form of Gaucher disease – diagnostic difficulties

“…The severity and progression of the swallow function may be a prognostic factor for the further course of the disease. Noticeable deterioration in swallowing is a common finding leading not only to cachexia but most often to aspiration pneumonia (Seehra et al, 2019). Type 3 GD varies greatly in terms of the complex of neurological symptoms and their severity.…”