Diagnosis of pseudoxanthoma elasticum following genomic re-analysis in a patient with chronic kidney disease: a case report

Abstract Purpose To describe a diagnosis of pseudoxanthoma elasticum following genomic re-analysis and to illustrate the challenge of determining whether chronic kidney disease represents an atypical manifestation of ABCC6-associated disease. Methods Following re-analysis of whole-genome sequencing data, historical renal, vascular, ophthalmic, laboratory and imaging records were reviewed. Reverse phenotyping was undertaken to assess the extent to which the patient’s multisystem features were consistent with pseudoxanthoma elasticum and to examine possible explanations for his chronic kidney disease. Results An older man with progressive chronic kidney disease, low-grade proteinuria, severe visual impairment and extensive large-vessel peripheral arterial disease was found to have compound heterozygous pathogenic ABCC6 variants, NM_001171.6 c.1741C>T; p.(Gln581Ter) and c.2787+1G>T. The diagnosis of pseudoxanthoma elasticum had not been recognized during life. His ocular and vascular disease were compatible with the phenotype of pseudoxanthoma elasticum; however, the renal phenotype was atypical. Renal ultrasonography and computed tomography showed chronic kidney disease without nephrolithiasis, nephrocalcinosis or renal calcification. Long-standing hypertension, severe vascular disease and a possible renovascular component remained plausible alternative explanations for renal impairment. Renal biopsy was not performed, and the diagnosis was made after the patient’s death, preventing targeted clinical reassessment. Conclusions Genomic re-analysis can identify previously unrecognized rare diseases and should prompt careful reverse phenotyping. In this case, the diagnosis of pseudoxanthoma elasticum explained important ocular and vascular features, but a direct causal relationship between ABCC6 deficiency and chronic kidney disease could not be established. This case supports further characterization of kidney phenotypes in individuals with biallelic ABCC6 variants.