De ziekte van Gaucher komt voor bij 1 op de 200.000 individuen en is daarmee één van de meest voorkomende lysosomale stapelingsziekten (Grabowski, 2008). Lysosomen zijn kleine intracellulaire compartimenten waarin de afbraak van macromoleculen plaatsvindt. Als door een genetisch defect de afbraak van bepaalde stoffen niet of onvoldoende gebeurt, leidt dit tot stapeling van het betreffende molecuul. De ziekte van Gaucher wordt veroorzaakt door een mutatie in het gen dat codeert voor glucocerebrosidase waardoor er stapeling van specifieke glycolipiden, vooral glucosylceramide (of glucocerebroside) in macrofagen optreedt. De ziekte wordt onderverdeeld in drie types: bij type 1 staan een vergrote lever en milt, trombocytopenie en botproblemen op de voorgrond. Type 2 wordt gekenmerkt door ernstige mentale retardatie en hypotonie. Meestal worden deze kinderen niet ouder dan twee jaar. Patiënten met de ziekte van Gaucher type 3 hebben vaak ernstige systemische ziekte, gecombineerd met een stoornis in de oogvolgbewegingen en meestal ook psychomotore achteruitgang. Er zijn meer dan 350 mutaties beschreven en er is geen duidelijke genotype-fenotyperelatie, hoewel patiënten met ten minste één N370S-mutatie vrijwel altijd type 1-gaucher hebben terwijl patiënten die homozygoot zijn voor de L444P-mutatie gewoonlijk type 2 of 3 hebben (Koprivica et al., 2000).
Abstract
Background
The absence of neurological symptoms and signs is traditionally considered mandatory for a diagnosis of type 1 Gaucher disease (GD1), but in recent years many reports have emerged on neurological manifestations in GD1 patients. Nevertheless, it has been unclear whether cognitive deficits are part of the disease as well.
Methods
Cognitive function was assessed in a large cohort of GD1 patients with the use of the Cognitive Drug Research system, a set of computerised cognitive tests. Testing was performed at baseline and every 6 months thereafter during a two-year study period.
Results
Our patient cohort (84 patients, median age 40 years, median time from diagnosis 15 years) showed mild deficits relative to healthy age-matched subjects on the composite scores: power of attention (Z-score [mean ± SD] -0.9±1.37) and speed of memory (Z-score [mean ± SD] -1.39±1.49). No decline in cognitive function was seen during the two-year period. Age correlated with the composite scores variability of attention and quality of working memory. Moreover, severely affected patients (Zimran severity score [SSI] ≥ 15) scored more poorly compared to mildly affected patients (SSI ≤ 5) on the composite measure power of attention, reflecting the ability to concentrate.
Conclusions
GD1 patients exhibit mild deficits in power of attention and speed of memory, reflecting a decreased ability to focus attention and process information, together with a slowing in the speed of retrieval of items from memory. The clinical relevance of these findings is uncertain; experience shows us that GD1 patients usually do not report difficulties in conducting daily activities, or cognitive problems. Moreover, the overall cognitive profile of GD1 patients is much less severely affected in comparison with the profile of patients suffering from dementia. Therefore, there is no need for doctors to monitor their patients or to take preventive measures.
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Mw. dr. M. Biegstraaten, arts-klinisch epidemioloog; mw. prof. dr. C.E.M. Hollak, internist erfelijke stofwisselingsziekten, Academisch Medisch Centrum, Afdeling Endocrinologie en Metabolisme, F5-166, Meibergdreef 9, 1105 AZ Amsterdam, E-mail: m.biegstraaten@amc.uva.nl.
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Biegstraaten, M., Hollak, C. Het cognitieve profiel van patiënten met de ziekte van Gaucher type 1. NEUROPRAXIS 17, 155–160 (2013). https://doi.org/10.1007/s12474-013-0029-5
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DOI: https://doi.org/10.1007/s12474-013-0029-5