ObjectiveTo estimate the prevalence of prodromal clinical features of neurodegeneration in patients with Anderson-Fabry disease (AFD) in comparison to age-matched controls.MethodsThis is a single-center, prospective, cross-sectional study in 167 participants (60 heterozygous females and 50 hemizygous males with genetically confirmed AFD, 57 age-matched controls) using a clinical screening program consisting of structured interview, quantitative tests of motor function, and assessments of cognition, depression, olfaction, orthostatic intolerance, pain, REM sleep behavior disorder, and daytime sleepiness.ResultsIn comparison to age-matched controls (mean age 48.3 years), patients with AFD (mean age 49.0 years) showed slower gait and transfer speed, poorer fine manual dexterity, and lower hand speed, which was independent of focal symptoms due to cerebrovascular disease. Patients with AFD were more severely affected by depression, pain, and daytime sleepiness and had a lower quality of life. These motor and nonmotor manifestations significantly correlated with clinical disease severity. However, patients with AFD did not reveal extrapyramidal motor features or signs of significant cognitive impairment, hyposmia, orthostatic intolerance, or REM sleep behavior disorder, which commonly precede later neurodegenerative disease. In our cohort, there were no differences in neurologic manifestations of AFD between heterozygous females and hemizygous males.ConclusionsAside from cerebrovascular manifestations and small fiber neuropathy, AFD results in a distinct neurologic phenotype comprising poorer motor performance and specific nonmotor features. In contrast to functional loss of glucocerebrosidase in Gaucher disease, α-galactosidase deficiency in AFD is not associated with a typical cluster of clinical features prodromal for neurodegenerative diseases, such as Parkinson disease.

This article evaluates satisfaction with enzyme replacement therapy (ERT) at home and at hospital in adult patients with Fabry and Gaucher diseases. A questionnaire was developed and sent to 34 patients with Fabry disease who were receiving ERT with agalsidase alfa (Replagal) and to 49 patients with type I Gaucher disease who were receiving ERT with glucocerebrosidase (Cerezyme). Of the 45 returned questionnaires, 20 were from patients with Fabry disease and 25 from patients with Gaucher disease. Hospital treatment visits were reported as stressful by 18 patients (40%), whereas only 4 (9%) patients reported that home therapy was stressful. Both groups of patients adjusted well to receiving home-based therapy. Nearly all of the patients with Fabry disease (19 patients, 95%) and Gaucher disease (21 patients, 84%) preferred home-based therapy. Treatment in the home was reported as more comfortable, less stressful, more effective and had less impact on family life. Only 4 (9%) patients chose to continue receiving infusions in hospital. The majority of patients with Fabry disease and Gaucher disease found home-based therapy to be more convenient and less stressful than hospital-based therapy.

Facial dysmorphology is an important feature in several lysosomal storage disorders. Although in Fabry disease facial dysmorphism is not a prominent sign, minor facial abnormalities have been previously reported. By analysing three-dimensional images of faces, we quantified facial dysmorphology in a cohort of both male and female Fabry patients. Morphometric analysis of different regions of the face revealed significant differences in face shape in male patients and to a lesser extent in female patients. In male patients, the most prominent abnormalities were located in the peri-orbital region. Pattern recognition techniques achieved a discrimination accuracy of up to 85% for male patients compared with healthy controls. The discrimination accuracy in female patients achieved only 67%. This objective method for facial dysmorphology assessment provided evidence for significant differences in face shape in both male and female Fabry patients compared with controls. However, because discrimination from healthy controls is too low, no key role in the diagnostic process can be expected.

These observations demonstrate a direct and measurable haemorheological abnormality in Gaucher disease only revealed when there is no functioning spleen to control erythrocyte quality.