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JIMD Rep. 2017;37:115-123. doi: 10.1007/8904_2017_22. Epub 2017 Apr 9.

Systematic Review and Meta-analysis of Intelligence Quotient in Early-Treated Individuals with Classical Galactosemia.

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Department of Pediatrics, Division of Metabolic Disorders, Academic Medical Center, University Hospital of Amsterdam, Amsterdam, The Netherlands.
Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Department of Psychology, Syracuse University, Syracuse, USA.
Department of Paediatrics, Trinity College, Dublin, Ireland.
University Children's Hospital, Pediatric Endocrinology, Diabetes and Metabolism, and Institute of Clinical Chemistry, Inselspital, University of Bern, Bern, Switzerland.
Metabolic Unit, Great Ormond Street Hospital and Institute of Child Health, University College London, NHS Trust, London, UK.
Clinical Research Unit, Academic Medical Center, Amsterdam, The Netherlands.
Pediatric Clinical Research Office, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
National Centre for Inherited Metabolic Disorders, Temple St. Children's University Hospital and Mater Misericordiae University Hospital, Dublin, Ireland.
Department of Pediatrics, Division of Metabolic Disorders, Academic Medical Center, University Hospital of Amsterdam, Amsterdam, The Netherlands.



Cognitive impairment is a well-known complication of classical galactosemia (CG). Differences in patient characteristics and test methods have hampered final conclusions regarding the extent of intellectual disabilities in CG. The primary aim of this systematic review was to assess intellectual performance in early-treated (≤4 weeks of life) individuals with confirmed CG (defined by absent or barely detectable GALT enzyme activity and/or the presence of two null or severe missense variations), assessed with comparable test instruments. The full-scale IQ (FSIQ) was the variable of interest.


A clinical librarian developed search strategies, and two independent investigators performed the study selection, risk of bias assessment and data extraction. Individual patient data were pooled for meta-analysis using linear mixed-effect models with a random intercept per study and including covariates (age or gender) as fixed effects where appropriate.


Four articles were included in this meta-analysis. Data of 87 individuals (median age 13 years, range 3-38 years) were used to assess mean FSIQ in CG. The FSIQ ranged from 47 to 122, and the mean score was 87 (95% CI, 81-94). Forty-five percent of individuals attained scores <85, almost 40% attained scores of 85-100, and a minority (15%) attained scores above 100. There was no significant correlation between FSIQ and age.


Results from this meta-analysis fortify conclusions from previous studies that early-treated individuals with CG are at risk for having impaired cognitive abilities. However, IQ varies considerably between affected individuals.


Classical galactosemia; Cognition; Intelligence quotient; Meta-analysis; Neuropsychological tests; Review

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