Abstract
Background
Classic galactosemia is an autosomal recessive disorder due to galactose-1-phosphate uridyltransferase (GALT) deficiency. Newborn screening and early treatment do not completely prevent tremor, speech deficits, and diminished IQ in both sexes and premature ovarian insufficiency (POI) in women. Data on how individuals with galactosemia fare as adults will improve our ability to predict disease progression.
Methods
Thirty-three adults (mean age = 32.6 ± 11.7 years; range = 18–59) with classic galactosemia, confirmed by genotype and undetectable GALT enzyme activity, were evaluated. Analyses assessed associations among age, genotype, clinical features and laboratory measures.
Results
The sample included 17 men and 16 women. Subjects exhibited cataracts (21%), low bone density (24%), tremor (46%), ataxia (15%), dysarthria (24%), and apraxia of speech (9%). Subjects reported depression (39%) and anxiety (67%). Mean full scale IQ was 88 ± 20, (range = 55–122). All subjects followed a dairy-free diet and 75–80% reported low intake of calcium and vitamin D. Mean height, weight and body mass were within established norms. All female subjects had been diagnosed with POI. One woman and two men had had children. Logistic regression analyses revealed no associations between age, genotype or gender with IQ, tremor, ataxia, dysarthria, apraxia of speech or anxiety. Each 10- year increment of age was associated with a twofold increase in odds of depression.
Conclusions
Taken together, these data do not support the hypothesis that galactosemia is a progressive neurodegenerative disease. However, greater attention to depression, anxiety, and social relationships may relieve the impact of this disorder in adults.
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Acknowledgments
This project was funded in part by a research grant from the Parents of Galactosemic Children, USA, and in part by the grant UL1 RR025758-01 from the National Center for Research Resources, National Institutes of Health, to the Harvard Catalyst Clinical & Translational Science Center (Harvard Catalyst). The authors thank the CTSU staff of Children's Hospital Boston for their superb assistance and the patients with galactosemia and their families who traveled to Boston from around the U.S.A. and participated in this study. We thank the Parents of Galactosemic Children, USA for their support. We also thank Al Ozonoff, Linda Manis, Michelle Fowler, Judith Muir, Catherine Arnold, Brian Deutsch, Stephanie Kon, Anya Kwasnik, and Rebecca Owen for their invaluable help.
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Communicated by: Sedel Frederic
Competing interest: None declared.
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Waisbren, S.E., Potter, N.L., Gordon, C.M. et al. The adult galactosemic phenotype. J Inherit Metab Dis 35, 279–286 (2012). https://doi.org/10.1007/s10545-011-9372-y
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DOI: https://doi.org/10.1007/s10545-011-9372-y