Familial pseudoxanthoma elasticum with nephrocalcinosis: a case report

• Autor(es): Lacerda, P. ; Beirão, I. ; Pestana, P. ; Beirão, J.M. ; Freitas, C. ; Rocha, M.J. ; Cabrita, A. ; Costa, P.P.
• Data: 2013
• Identificador Persistente: http://hdl.handle.net/10400.18/2213
• Origem: Repositório Científico do Instituto Nacional de Saúde
• Assunto(s): Pseudoxanthoma Elasticum; PXE; Nephrocalcinosis; Case Report; ABCC6; Doenças Genéticas
• Tipo de Documento: Documento de conferência
• Idioma: Inglês

Descrição

Pseudoxanthoma elasticum (PXE) is an autosomal recessive genetic disorder characterized by progressive calcification and fragmentation of elastic fibres. PXE commonly involves the reticular dermis, the Bruch membrane of the eye, and blood vessels. PXE is caused by mutations in the ABCC6 gene. More than 300 pathogenic ABCC6 mutations are known. Two of these mutations are common: p.R1141X in exon 24, with a prevalence of 30%, and the Alu–mediated deletion of exons 23 to 29 (EX23_29del; p.A999_S1403del) found in 10-20% of patients. Homozygosity is rare. A 40-year-old female with a previous diagnosis of PXE was admitted in Nephrology Outpatient Clinic for nephrocalcinosis. She has two sisters, one of which also has a diagnosis of PXE and nephrocalcinosis. Physical examination revealed the presence of typical skin and ocular abnormalities. Microscopic and gross hematuria was reported in both affected sisters. Abdominal ultrasound confirmed bilateral cortico-medullar nephrocalcinosis. Calcium and phosphorus levels in blood and urine were normal. Hyperparathyroidism, renal tubular acidosis, hypervitaminosis D and hyperoxaluria were excluded. Renal biopsy showed only minor glomerular abnormalities. Medullary sponge kidney was identified by excretory urography. Genomic DNA was used as a template for PCR amplification of the region spanning introns 22 to 29 of ABCC6 [Pfendner et al., J Med Genet 2007;44:621-8]. The oligonucleotide cocktail used generated a 552bp PCR product for the normal sequence, and a 652bp product for the deletion mutation. Both sisters with PXE were homozygous for the EX23_29del mutation. The third sister did not carry this deletion. There are occasional reports of diffuse visceral calcifications (testis, mammary gland) in PXE. PXE-associated nephrocalcinosis was previously noted in four patients belonging to different families. This is the first report of familiar co-occurrence of PXE and nephrocalcinosis with medullary sponge kidney. These sisters’ peculiar phenotype could be due to their unusual genotype, or other shared genetic and environmental factors.