Characterization of the renal phenotype in RMND1-related mitochondrial disease - PubMed (original) (raw)

Case Reports

doi: 10.1002/mgg3.973. Epub 2019 Sep 30.

Nhon T Le 3, Nasim Bekheirnia 1 3 4, Jill A Rosenfeld 2, Amy C Goldstein 5, Michael Moritz 6, Dennis W Bartholomew 7, Matthew T Pastore 7, Fan Xia 2 8, Christine Eng 2 8, Yaping Yang 2 8, Dolores J Lamb 3 9, Fernando Scaglia 1 2 10, Michael C Braun 1 3 4, Mir Reza Bekheirnia 1 2 3 4

Affiliations

Case Reports

Brian J Shayota et al. Mol Genet Genomic Med. 2019 Dec.

Abstract

Background: The nuclear encoded gene RMND1 (Required for Meiotic Nuclear Division 1 homolog) has recently been linked to RMND1-related mitochondrial disease (RRMD). This autosomal recessive condition characteristically presents with an infantile-onset multisystem disease characterized by severe hypotonia, global developmental delay, failure to thrive, sensorineural hearing loss, and lactic acidosis. Renal disease, however, appears to be one of the more prominent features of RRMD, affecting patients at significantly higher numbers compared to other mitochondrial diseases. We report the clinical, histological, and molecular findings of four RRMD patients across three academic institutions with a focus on the renal manifestations.

Methods: Four patients were identified for the purpose of this study, all of whom had molecular confirmation at the time of inclusion, which included the common pathogenic variant c.713A>G (p.N238S) as well as the three rare variants: c.485delC (p.P162fs), c.533C>T (p.T178M), and c.1317 + 1G>C splice donor variant. Medical history and laboratory findings were collected from the medical records and medical providers.

Results: In this study, all four patients developed renal disease characterized as tubulopathy (3/4), renal tubular acidosis (2/4), interstitial nephritis (1/4), and/or end-stage renal disease (4/4) necessitating renal transplantation (2/4). Histological evaluation of renal biopsy specimens revealed generalized tubular atrophy and on electron microscopy, abundant mitochondria with pleomorphism and abnormal cristae.

Conclusion: Our experience with RRMD demonstrates a specific pattern of renal disease manifestations and clinical course. Patients are unlikely to respond to traditional chronic kidney disease (CKD) treatments, making early diagnosis and consideration of renal transplantation paramount to the management of RRMD.

Keywords: RMND1; Mitochondrial disease; chronic kidney disease; renal transplantation.

© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1

Figure 1

Histology of renal biopsy specimen of patient 4 reveals tubular atrophy consistent with the most common renal phenotype related to RMND1. (a) A PAS stain image showing areas of tubular atrophy with no significant glomerular disease. Note thyroidization of some of the tubules and the interstitial widening (PAS, 20×). (b) A Masson trichrome stain showing interstitial fibrosis and separation of tubules with some interstitial inflammation. (Masson 10×). (c) An electron micrograph showing a low magnification view of tubular epithelial cell with abundant mitochondria (9,080×). (d) A higher magnification image showing some variability in size and shape of mitochondria but no significant inclusions or pathologic changes. (23,700×)

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