Abstract
ContextFabry Disease (FD) is a rare X-linked storage disease characterised by a-galactosidase A deficiency and diffuse organ accumulation of glycosphingolipids. Enzyme replacement and chaperone therapies are only partially effective. It remains unclear if FD-related endocrine disorders contribute to the observed morbidity.ObjectiveTo investigate the function of the endocrine system in patients with FD.DesignWe conducted an observational prospective study from 2017 to 2020.Setting and patientsWe included 77 patients with genetically confirmed FD (27 men, 20/27 Classic, 7/26 Late Onset phenotype, 50 women, 41/50 and 9/50 respectively), who are systematically followed by our reference centre.Results36/77 (46.8%) patients had VitD deficiency (25(0H)VitD <20 μg/L) despite the fact that 19/36 (52.8%) were substituted with cholecalciferol. Only 21/77 (27.3%) patients had normal VitD levels without VitD substitution. 11/77 (14.3%) had significant hypophosphatemia (p < 0.80 mmol/L). Three new cases (3.9%) of subclinical, two (2.6%) of overt and six (7.8%) of known hypothyroidism were identified. Of note, men had significantly higher renin levels than women [61.4 (26.1–219.6) vs.25.4 (10.9–48.0) mU/L, p = 0.003]. There were no major abnormalities in adrenal, growth and sex-hormone axes. Patients of Classic phenotype had significantly higher High-Density Lipoprotein Cholesterol (HDL-C) levels (p = 0.002) and in men those levels were positively correlated with globotriaosylsphingosin (Lyso-Gb3) values. 10/77 (13%) of the patients were underweight.ConclusionsVitD supplementation should be considered for all patients with FD. Thyroid screening should be routinely performed. Malnutrition should be prevented or treated, particularly in Classic phenotype patients. Overall, our data suggest that FD specialists should actively seek and diagnose endocrine disorders in their patients.
Highlights
IntroductionGlobotriaosylceramide (Gb3) and other related glycosphingolipids are accumulated in the defective lysosomes of the patients who progressively develop diffuse organ damage [2]
Fabry Disease (FD) is a rare X- linked storage disease caused by mutations in the a-galactosidase A (GLA) gene leading to reduced activity of the encoded lysosomal enzyme (α-Galactosidase Α, α-Gal) [1]
The patient group consisted of 27 men, 20 with the Classic and 7 with the Late Onset phenotype and 50 women, 41 of the Classic and 9 Late Onset phenotype
Summary
Globotriaosylceramide (Gb3) and other related glycosphingolipids are accumulated in the defective lysosomes of the patients who progressively develop diffuse organ damage [2]. In the Classic phenotype, males with little or no residual α-Gal A activity develop disease signs and symptoms already in childhood. These include acroparesthesias, angiokeratoma, corneal opacities, Endocrine hypohidrosis and gastrointestinal symptoms. Accumulation of Gb3 and related glycoshingolipid metabolites in the different organs result in cardiac and renal complications as well as early strokes [3]. Males with the Late Onset phenotype have residual enzymatic activity and lack symptoms in childhood, they develop cardiac or, less frequently, renal manifestations usually later in adulthood. Females with FD are heterozygotes for the gene and may present with variable manifestations of FD, ranging from asymptomatic to severe, due to the skewed inactivation of the affected X-chromosome [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
