Delayed diagnoses of mitochondrial cytopathies in patients presenting with end stage kidney disease: two case reports
- PDF / 1,085,783 Bytes
- 7 Pages / 595.276 x 790.866 pts Page_size
- 46 Downloads / 213 Views
CASE REPORT
Open Access
Delayed diagnoses of mitochondrial cytopathies in patients presenting with end stage kidney disease: two case reports Tayeba Roper1* , Mark Harber2, Gareth Jones2, Robert D. S. Pitceathly3 and Alan D. Salama2
Abstract Background: Up to one third of patients on renal replacement programmes have an unknown cause of kidney disease, and the diagnosis may only be established following renal transplantation when the disease recurs or if new extra-renal symptoms develop. Case presentation: We present two patients who presented with progressive chronic kidney disease of unknown cause. Both patients underwent successful renal transplantation but subsequently developed multisystem abnormalities, and were ultimately diagnosed with mitochondrial cytopathy 10–15 years following transplantation. Conclusions: Mitochondrial cytopathies are rare inborn errors of metabolism that should be considered in adults with renal impairment, especially in those with a family history of kidney or other multisystem disease. The widespread availability of genetic testing provides the potential for earlier diagnoses, thereby enhancing management decisions, anticipation of complications, avoidance of mitotoxic drugs, and informed prognosis prediction. Keywords: End stage renal disease, Mitochondrial cytopathies, Primary mitochondrial disease, Renal transplant, Delayed diagnoses, Inherited conditions, Multisystem disorders
Background Mitochondrial cytopathies (MC), also known as primary mitochondrial diseases (PMD), are a rare heterogenous group of conditions, defined by sporadic or inherited mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA), that encode for proteins required for mitochondrial function [1]. Consequently, MC may follow maternal or Mendelian inheritance patterns, depending on the location of the mutant gene [2]. During mitosis the distribution of mtDNA to daughter cells is uneven, and so cells often contain a mixture of both mutant and wild-type mtDNA [3]. Cells are therefore either homo- or heteroplasmic with regard to mutations, * Correspondence: [email protected] 1 Department of Renal Medicine, Guy’s & St Thomas’ NHS Foundation Trust, Great Maze Pond, London, UK Full list of author information is available at the end of the article
i.e. contain entirely mutant mtDNA, or a varying amount of both wild-type and mutant mtDNA, respectively [4]. The overall frequency of mtDNA mutations in adults is estimated to be 1:5000 [5]. MC are often multisystem disorders and frequently affect organs or tissues with high metabolic demand, such as the brain, heart and skeletal muscle [4, 6]. MC can present as Mitochondrial Cytopathy Syndromes (MCS) affecting multiple organs, with certain clinical features occurring in clusters. Several different MCS have been reported (Table 1), however the majority of MC do not fall within these clinical entities [10]. Furthermore, different genotypes can present with the same phenotype (Table 1), which may be related to different penetrance associated with mtDNA heterop
Data Loading...
