Classical galactosemia Cognitive, psychosocial and prognostic challenges

Classical galactosemia (CG) is an autosomal recessive inborn error of galactose metabolism caused by a severe deficiency of the enzyme galactose-1-phosphate-uridyltransferase (GALT). In affected newborns, ingestion of galactose from breast milk or infant formula causes life-threatening symptoms. An early diagnosis after newborn screening (NBS) or family screening and a timely initiation of a lifelong lactose-free and galactose-restricted diet resolves the symptoms and prevents critical illness. However, in spite of an early diagnosis and treatment CG-patients develop long-term complications including cognitive deficits, psychosocial problems, motor disorders and primary ovarian insufficiency in varying degrees of severity.
Part 1 of this thesis addresses in-depth the cognitive and psychosocial outcome of patients with CG. The cognitive outcome of CG is investigated by systematically reviewing the scientific literature, by examining the cognitive profile of CG through an extensive neuropsychological assessment in our Dutch cohort, and by performing a small longitudinal study to examine cognitive stability in adult patients. The psychosocial outcome of CG is investigated by examining social cognition, cognitive functioning and emotion-regulation together in a homogenous sample of CG-patients without intellectual disabilities.
Part 2 of this thesis addresses the clinical outcome from the perspective of the CG-patients and their parents by examining the health-related quality of life.
Part 3 of this thesis focuses on a new approach to obtain insights in the pathophysiology of CG. We used technological advanced techniques to study metabolites in small molecules (metabolomics) and complex lipids (lipidomics) in erythrocytes in order to gain more understanding of the underlying biochemical abnormalities.