Progression & Prognosis

The progressive organ and tissue damage associated with Fabry disease may result in substantially decreased life expectancy. As shown in the figure below, median cumulative survival has been reported as 50 years in males and 70 years in females, representing a 20-year and 15-year reduction (respectively) in life span compared with data from the general population. MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet 2001;38:769–75.<br /> MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet 2001;38:750–60.<br />

Impact of Fabry disease on average life span using the Kaplan-Meier survival method.

Adapted from MacDermot (2001) MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet 2001;38:769–75.<br /> MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet 2001;38:750–60.<br />

Classical or non-classical phenotype

Growing evidence indicates there may be a significant number of  ‘non-classical phenotypes’ or ‘atypical phenotypes’. These are patients who may have none or few of the hallmark symptoms of classical Fabry disease. Van der Tol, L. et al. A systematic review on screening for Fabry disease: prevalence of individuals with genetic variants of unknown significance. J Med Genet.  Patients with non-classical (atypical) phenotypes of Fabry disease typically have residual plasma α-galactosidase A (α-GAL) levels (enzyme activity >5% of the mean reference range and none of the characteristic Fabry disease symptoms, i.e. Fabry neuropathic pain, angiokeratoma and/or cornea verticillata) and usually present later in life than those with  classical Fabry disease Germain DP. Fabry Disease. Orphanet J Rare Dis. 2010;5:30. They are often identified serendipitously, and may have manifestations predominately in one organ system.