Deep phenotyping classical galactosemia: clinical outcomes and biochemical markers.

Autor:	Welsink-Karssies MM; Division of Metabolic Disorders, Department of Pediatrics, Emma Children's Hospital, Amsterdam, UMC, University of Amsterdam, Amsterdam, the Netherlands., Ferdinandusse S; Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Geurtsen GJ; Department of Medical Psychology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Hollak CEM; Division of Endocrinology and Metabolism, Department of Internal Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Huidekoper HH; Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus, MC, University Medical Center, Rotterdam, the Netherlands., Janssen MCH; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands., Langendonk JG; Department of Internal Medicine, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Centre, Rotterdam, the Netherlands., van der Lee JH; Pediatric Clinical Research Office, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Knowledge Institute of the Dutch Association of Medical Specialists, Utrecht, the Netherlands., O'Flaherty R; NIBRT GlycoScience Group, National Institute for Bioprocessing, Research and Training, Mount Merrion, Blackrock, County Dublin, Ireland., Oostrom KJ; Psychosocial Department, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Roosendaal SD; Department of Radiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Rubio-Gozalbo ME; Department of Pediatrics, Maastricht University Medical Center, Maastricht, the Netherlands.; Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands., Saldova R; Knowledge Institute of the Dutch Association of Medical Specialists, Utrecht, the Netherlands.; UCD School of Medicine, College of Health and Agricultural Science, University College Dublin, Dublin, Ireland., Treacy EP; National Centre for Inherited Metabolic Disorders, The Mater Misericordiae University Hospital, Dublin, Ireland., Vaz FM; Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., de Vries MC; Department of Pediatrics, Radboud University Medical Center, Nijmegen, the Netherlands., Engelen M; Department of Pediatric Neurology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Bosch AM; Division of Metabolic Disorders, Department of Pediatrics, Emma Children's Hospital, Amsterdam, UMC, University of Amsterdam, Amsterdam, the Netherlands.
Jazyk:	angličtina
Zdroj:	Brain communications [Brain Commun] 2020 Jan 29; Vol. 2 (1), pp. fcaa006. Date of Electronic Publication: 2020 Jan 29 (Print Publication: 2020).
DOI:	10.1093/braincomms/fcaa006
Abstrakt:	Early diagnosis and dietary treatment do not prevent long-term complications, which mostly affect the central nervous system in classical galactosemia patients. The clinical outcome of patients is highly variable, and there is an urgent need for prognostic biomarkers. The aim of this study was first to increase knowledge on the natural history of classical galactosemia by studying a cohort of patients with varying geno- and phenotypes and second to study the association between clinical outcomes and two possible prognostic biomarkers. In addition, the association between abnormalities on brain MRI and clinical outcomes was investigated. Classical galactosemia patients visiting the galactosemia expertise outpatient clinic of the Amsterdam University Medical Centre were evaluated according to the International Classical Galactosemia guideline with the addition of an examination by a neurologist, serum immunoglobulin G N -glycan profiling and a brain MRI. The biomarkers of interest were galactose-1-phosphate levels and N -glycan profiles, and the clinical outcomes studied were intellectual outcome and the presence or absence of movement disorders and/or primary ovarian insufficiency. Data of 56 classical galactosemia patients are reported. The intellectual outcome ranged from 45 to 103 (mean 77 ± 14) and was <85 in 62%. Movement disorders were found in 17 (47%) of the 36 tested patients. In females aged 12 years and older, primary ovarian insufficiency was diagnosed in 12 (71%) of the 17 patients. Significant differences in N -glycan peaks were found between controls and patients. However, no significant differences in either N -glycans or galactose-1-phosphate levels were found between patients with a poor (intellectual outcome < 85) and normal intellectual outcome (intellectual outcome ≥ 85), and with or without movement disorders or primary ovarian insufficiency. The variant patients detected by newborn screening, with previously unknown geno- and phenotypes and currently no long-term complications, demonstrated significantly lower galactose-1-phospate levels than classical patients ( P  < 0.0005). Qualitative analysis of the MRI's demonstrated brain abnormalities in 18 of the 21 patients, more severely in patients with a lower intellectual outcome and/or with movement disorders. This study demonstrates a large variability in clinical outcome, which varies from a below average intelligence, movement disorders and in females primary ovarian insufficiency to a normal clinical outcome. In our cohort of classical galactosemia patients, galactose-1-phosphate levels and N -glycan variations were not associated with clinical outcomes, but galactose-1-phosphate levels did differentiate between classical and variant patients detected by newborn screening. The correlation between brain abnormalities and clinical outcome should be further investigated by quantitative analysis of the MR images. The variability in clinical outcome necessitates individual and standardized evaluation of all classical galactosemia patients. (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)
Databáze:	MEDLINE
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