Movement Disorders in Classic Galactosemia 公开

Abstract

Movement disorders in classic galactosemia

More than one hundred infants with classic galactosemia are born each year in the United States alone. In this autosomal recessive disorder, mutations impair galactose metabolism, causing acute complications with high morbidity and mortality as soon as the infant begins a milk-based diet. Removing galactose from the diet is a critical, lifesaving intervention; yet this treatment does not prevent multiple long-term complications. Long-term neurological outcomes, particularly movement disorders, have been reported but not well studied. This project was sparked by a request from a parent and galactosemia community organizer for a neurologist to help understand causes and possible treatments of tremor in classic galactosemia. We conducted a cross sectional observational study of 45 classic galactosemia patients, including both children and adults, and patients diagnosed with newborn screening or after initial symptoms. We report a range of movement disorders, including action and postural tremor, dystonia and limb ataxia, in children and adults. Bradykinesia was also common, but other parkinsonian features were not observed. Chorea was unusual, as was gait impairment. Most affected areas were limbs, and neck. Gender did not associate with neurological outcome; however, there were trends towards older age at time of neurological exam and symptomatic at diagnosis associating with affected neurological outcome. We used our own laboratory assays to determine genotype and predicted residual enzyme activity for each subject. As in other largely Caucasian classic galactosemia cohorts, the Q188R mutation was by far the most common. There was no clear association between genotype and neurological outcome. Results for GALT enzyme activity and age at diet intervention had weak trends opposite of biological theories in the field; in both cases outliers had a large impact on the results. The pilot results will prove very useful in designing and conducting a larger, longitudinal, multi-center study.

Table of Contents

TABLE OF CONTENTS
Introduction...1
Background...3
Methods...9
Results...17
Discussion...22
References...31

Figure 1...35
Figure 2...36
Figure 3...37
Figure 4...38
Figure 5...39
Figure 6...40
Figure 7...41

Table 1...42
Table 2...43
Table 3...44

Appendix...45

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research Curriculum Program
Degree	MS
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Medicine and Surgery
关键词	ataxia neurology dystonia galactosemia tremor
Committee Chair / Thesis Advisor	Fridovich-Keil, Judith, Emory University Factor, Stewart, Emory University
Committee Members	Boring, John R, Emory University Klein, Mitchel, Emory University

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