Exploring Potential Correlations Among Developmental Deficits Experienced by Patients with Classic Galactosemia Open Access

Abstract

Classic galactosemia (CG) is an inborn error in metabolism of galactose, which results from a deficiency of galactose-1-phosphate uridylyltransferase (GALT) activity. Without treatment, CG gives rise to acute symptoms such as poor feeding, frequent vomiting, frequent diarrhea, poor weight gain, jaundice, and other acute symptoms including E. coli sepsis, which can be fatal. Adverse long-term outcomes in the speech, cognitive, motor/neurological, female puberty/reproduction, and growth/ bone health domains are still probable despite acute symptom prevention and dietary treatment. These long-term complications demonstrate incomplete penetrance and variable expressivity among patients – even those with exactly the same GALT genotype. The primary goal of this study is to determine whether the long-term outcomes in CG cluster. Results indicated that among the cognitive, speech, and motor/neurological outcome domains for both cases and controls, a strong clustering effect was observed in both the summary score and Vineland Test data. Although similar clustering effects were present, the CG cases experienced more severe adverse outcomes overall. Thus, if a participant with a CG diagnosis had an adverse outcome in a cognitive, speech, or motor/neurological domain, it is more likely that the participant also experienced one or more adverse outcomes in the other domains. These results suggest that shared modifiers may underlie multiple outcome domains in CG.

Table of Contents

CHAPTER 1: Background and Introduction to Classic Galactosemia ............................................. 1

What is Classic Galactosemia? .......................................................................................... 1

Genetics and Prevalence ................................................................................................... 1

Metabolic Findings ............................................................................................................ 2

Acute Symptoms ............................................................................................................... 2

Long-Term Complications Despite Standard Care of Treatment ...................................... 3

Current Understanding of the Onset, Prevalence & Mechanisms of Long-Term Complications in Relation to Possible Modifiers .................................... 3

Cognitive Defects .................................................................................................. 3

Speech Defects ...................................................................................................... 4

Motor/Neurological Defects ................................................................................. 4

Puberty/Reproduction .......................................................................................... 5

Growth/Bone Health ............................................................................................. 6

Socioemotional/Behavioral Problems ................................................................... 6

Possible Modifiers ................................................................................................. 7

Relevance of Investigating Possible Associations and Independence of Different Outcomes ............................................. 8

CHAPTER 2: Study Methods ........................................................................................................ 11

Study Participants ........................................................................................................... 11

Statistical Methods ......................................................................................................... 12

Vineland Test Data .......................................................................................................... 13

Statistical Tests Completed ............................................................................................. 14

CHAPTER 3: Results ..................................................................................................................... 16

Summary Score Analyses ……………………………………………………………..…………….................. 16

Shapiro-Wilk Test for Normality ………………………………..……………......................... 16

Wilcoxon Rank Sum Test with Continuity Correction ......................................... 16

Linear Regression Results..................................................................................... 22

Vineland Data Analyses …………………………………...........………………………..…………...........................29

CHAPTER 4: Discussion and Conclusion ...................................................................................... 38

APPENDIX .................................................................................................................................... 41

REFERENCES ................................................................................................................................ 43

About this Honors Thesis

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School	Emory College
Department	Human Health
Degree	B.A.
Submission	Honors Thesis
Language	English
Research Field	Health Sciences, General Biology, Genetics
Keyword	Galactosemia Prevalence Modifiers
Committee Chair / Thesis Advisor	Dr. Judith Fridovich-Keil, Emory University
Committee Members	Dr. Jill Welkley, Emory University Dr. Myra Woodworth-Hobbs, Emory University

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