Objective: To describe the renal ultrasonography (US) and magnetic resonance imaging (MRI) findings in affected males and female carriers with the classic and cardiac variant phenotypes of Fabry disease (alpha-galactosidase A [alpha-Gal A] deficiency).
Methods: The renal US and MRI features of 76 classically affected males (aged 7-53 years), 40 female carriers from classically affected families (aged 18-66 years), and 6 males with the cardiac variant phenotype (aged 17-59 years) were reviewed by 3 blinded board-certified radiologists. The images were evaluated for the presence of cortical cysts, parapelvic cysts, renal atrophy, decreased cortical thickness, increased echogenicity (US only), and decreased corticomedullary differentiation (MRI only). The consensus findings were analyzed with respect to the patients' sex, age, Fabry genotype and phenotype, and renal function.
Results: MRI was more sensitive than US in detecting radiographic abnormalities. In the 76 classically affected males, the most common US abnormalities were cysts (36.9%; cortical cysts = 22.4%, parapelvic cysts = 14.5%), increased echogenicity (17.1%), and decreased cortical thickness (11.9%), whereas the most common MRI abnormalities were cysts (47.3%; cortical cysts = 28.9%, parapelvic cysts = 18.4%), loss of corticomedullary differentiation (43.4%), and decreased cortical thickness (7.9%). Among the 40 female carriers, common US abnormalities included cysts (20%; cortical cysts = 10%, parapelvic cysts = 10%) and increased echogenicity (7.5%), whereas MRI findings included decreased corticomedullary differentiation (40%) and cysts (37.5%; cortical cysts = 20%; parapelvic cysts = 17.5%). Renal US and MRI were normal in 5 classically affected males aged 12 years or younger and 2 female carriers aged 20 years or younger. Among the 6 male cardiac variants, abnormal US findings included cysts (66.3%; cortical cysts = 50%, parapelvic cysts = 16.3%) and increased echogenicity (33.3%), whereas MRI detected decreased corticomedullary differentiation in all (100%) and cysts in 83% (cortical cysts = 66.7%; parapelvic cysts = 16.3%). Serum creatinine levels were elevated (>1.2 mg/dL) in 40.8% and 15% of the classically affected males and female carriers with US and/or MRI abnormalities compared with 14.8% and 0%, respectively, who had elevated serum creatinine levels but no detectable radiographic abnormalities. There was no association of alpha-Gal A genotype with type or frequency of abnormalities in classically affected patients.
Conclusions: Among classically affected males and female carriers, renal US and/or MRI abnormalities were detected in 64.5% and 60%, respectively. The occurrence and number of abnormalities increased with age in affected males and female carriers. Cysts, particularly parapelvic cysts, were more common and appeared earlier than in the general population. No renal abnormalities were detected in classically affected males or female carriers <12 years or <20 years of age, respectively. Five of the 6 males with the later-onset milder cardiac variant phenotype had loss of corticomedullary differentiation on MRI. Renal imaging abnormalities were more frequent in older patients with elevated serum creatinine levels, regardless of alpha-Gal A genotype or Fabry phenotype.