Publication
Homozygosity for a rare FASTKD2 variant resulting in an adult onset autosomal recessive mitochondrial podocytopathy
| dc.contributor.author | Gonçalves, Francisco Pereira | |
| dc.contributor.author | Tavares, Isabel | |
| dc.contributor.author | Silva, Roberto | |
| dc.contributor.author | Nunes, Ana Teresa | |
| dc.contributor.author | Pereira, Luciano | |
| dc.contributor.author | Campos, Andreia | |
| dc.contributor.author | Pinto, Joel | |
| dc.contributor.author | Lopes, Ana | |
| dc.contributor.author | Simões, Marta | |
| dc.contributor.author | Grazina, Manuela | |
| dc.contributor.author | Fogo, Agnes B. | |
| dc.contributor.author | Oliveira, João Paulo | |
| dc.date.accessioned | 2025-11-21T16:37:56Z | |
| dc.date.available | 2025-11-21T16:37:56Z | |
| dc.date.issued | 2025-01 | |
| dc.description.abstract | Mitochondrial cytopathies can have kidney involvement in up to half of cases. Their diagnosis is challenging due to phenotypic variability, lack of noninvasive tests to assess mitochondrial dysfunction, and genetic heterogeneity. We report on a young adult male with hypertrophic cardiomyopathy (HCM) and chronic kidney disease (CKD) with subnephrotic proteinuria who presented to the emergency department with kidney failure and hypervolemia requiring dialysis. A kidney biopsy showed focal segmental and global glomerulosclerosis, extensive foot process effacement, and abnormal mitochondria in podocytes and tubular epithelial cells; the genetic workup identified a rare FASTKD2 exon 2 variant, c.29G>C p.(Ser10Thr), in homozygosity; and functional mitochondrial assays in cultured skin fibroblasts showed reduction in FASTKD2 protein expression and moderate combined impairment in mitochondrial respiratory chain (MRC) assembly and function. This is the first report of a FASTKD2-associated cardiorenal mitochondrial cytopathy, characterized by young adult-onset proteinuric CKD and dilated HCM, in the absence of the severe neurologic manifestations described in patients with biallelic FASTKD2 variants. We hypothesize that the increased production of reactive oxygen species associated with moderate MRC impairment could result in a smoldering podocytopathy with progressive proteinuric CKD, without overt tubulopathy or encephalomyopathy—which might be, instead, pathogenically related to adenosine triphosphate deficiency. | por |
| dc.identifier.citation | Gonçalves, F. P., Tavares, I., Silva, R., Nunes, A. T., Pereira, L., Campos, A., Pinto, J., Lopes, A., Simões, M., Grazina, M., Fogo, A. B., & Oliveira, J. P. (2025). Homozygosity for a Rare FASTKD2 Variant Resulting in an Adult Onset Autosomal Recessive Mitochondrial Podocytopathy. American Journal of Kidney Diseases, 85(1), 119–123. https://doi.org/10.1053/j.ajkd.2024.05.018 | |
| dc.identifier.doi | 10.1053/j.ajkd.2024.05.018 | |
| dc.identifier.eissn | 1523-6838 | |
| dc.identifier.issn | 0272-6386 | |
| dc.identifier.uri | http://hdl.handle.net/10400.22/31032 | |
| dc.language.iso | eng | |
| dc.peerreviewed | yes | |
| dc.publisher | Elsevier | |
| dc.relation.hasversion | https://www.sciencedirect.com/science/article/pii/S0272638624008977?via%3Dihub | |
| dc.rights.uri | N/A | |
| dc.subject | HCM | |
| dc.subject | CKD | |
| dc.subject | FASTKD2 | |
| dc.title | Homozygosity for a rare FASTKD2 variant resulting in an adult onset autosomal recessive mitochondrial podocytopathy | por |
| dc.type | research article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 123 | |
| oaire.citation.issue | 1 | |
| oaire.citation.startPage | 119 | |
| oaire.citation.title | American Journal of Kidney Diseases | |
| oaire.citation.volume | 85 | |
| oaire.version | http://purl.org/coar/version/c_970fb48d4fbd8a85 |