Gurpreet Seehra1, Beth Solomon2, Emory Ryan1, Alta M Steward1, Tamanna Roshan Lal1, Yuichiro Tanima1, Grisel Lopez1, Ellen Sidransky3. 1. Section on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States of America. 2. Speech and Language Pathology Section, Rehabilitation Medicine Department, Mark O. Hatfield Clinical Research Center, NIH, DHHS, Bethesda, MD, United States of America. 3. Section on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States of America. Electronic address: sidranse@mail.nih.gov.
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. Published by Elsevier Inc.
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. Published by Elsevier Inc.
Authors: Ozlem Goker-Alpan; Raphael Schiffmann; Joseph K Park; Barbara K Stubblefield; Nahid Tayebi; Ellen Sidransky Journal: J Pediatr Date: 2003-08 Impact factor: 4.406