Mitochondrial Disease in Children: The Nephrologist’s Perspective

Abstract

Mitochondrial diseases (MD) are a heterogeneous group of clinical syndromes characterized by the involvement of different organ systems. They constitute the most prevalent hereditary metabolic disease group.

Objective: To review the importance of the kidney in MD from the nephrologist’s perspective within the setting of a pediatric tertiary reference center.

Study design: Retrospective study of children (<18 years) with MD followed between 2000 and 2016 at a tertiary Spanish center.

Results: 52 patients were included. The mean age at the time of the study was 10 years (SD ± 5.1). The mean follow-up time was 6.1 years (SD ± 4.7). The median age at diagnosis was 2.5 years (0.3–13.5).

The median number of affected systems was two (range 1–6). The nervous system was the most affected system, with 51 patients (~98%) presenting with neurological involvement. 20 patients (~40%) presented with endocrinological manifestations, 18 (~35%) with vision problems, 16 (~30%) with gastrointestinal symptoms, 5 (~10%) patients developed hearing impairment, and 6 (~10%) cardiac disease.

We detected renal involvement in 13 patients (25%). Eight patients had tubular disease, most frequently hypercalciuria with hypouricemia and five patients had glomerular involvement, with proteinuria and/or decreased glomerular filtration rate as the most frequent symptoms. Only 21 patients (~40%) had been seen by a pediatric nephrologist.

Conclusions: Renal disease was a common occurrence in patients with mitochondrial disease, present in our study in 25% of patients. A regular screening of renal function parameters and the involvement of a nephrologist as part of the multidisciplinary approach to mitochondrial disease appears warranted.

Appendices

Additional Information Tables: Laboratory Reference Parameters for Children

Table 5 Estimated glomerular filtration rate (GFR) (mean ± SD) (Santos and García Nieto 2006)

Table 6 Plasma creatinine levels (Hospital’s laboratory reference values n.d.)

Table 7 Plasma uric levels (Hospital’s laboratory reference values n.d.)

Table 8 Plasma phosphate levels (Hospital’s laboratory reference values n.d.)

Table 9 Urinary Ca/Cr ratios (Santos and García Nieto 2006)

Original Scwartz formula: GFR (mL/min/1.73 m²) = K (age-dependent) × height (cm)/Creatinine (mg/dL). K = 0.33 (preterm infants 0–1 year); 0.45 (full-term infants 0–1 years); 0.55 (1–12 years); 0.70 (male >12 years) and 0.55 (female >12 years).

Synopsis

Renal involvement in mitochondrial diseases can affect the different segments of the nephron, leading to a broad spectrum of symptoms; thus, a close follow-up of the renal function is recommended in these children.

Authors Contributions

PP and CdL designed the study; PP, CdL, and MAF conducted the study and wrote the manuscript; TdR contributed to the analysis and reporting of the results; CdL, TdR, CA, and LGS supervised the study and critically reviewed the manuscript. All authors read and approved the final manuscript.

Corresponding Author

Paula Pérez-Albert.

Conflict of Interest

Paula Pérez-Albert, Carmen de Lucas Collantes, Miguel Ángel Fernández-García, Teresa de Rojas, Cristina Aparicio López, and Luis Gutiérrez-Solana declare that they have no conflict of interest.

Funding

The authors confirm independence from the sponsors; the content of the chapter has not been influenced by the sponsors.

Ethics Approval

This study has been carried out in accordance with the ethical standards approved by the ethical committee of the Niño Jesús Hospital, which is in accordance with the national committee on human experimentation and the Helsinki Declaration of 1975 and the revised version of 2015. For this retrospective study, formal consent was not required by the ethics committee.