Diffuse mesangial sclerosis in a PDSS2 mutation-induced coenzyme Q10 deficiency

Pediatr Nephrol. 2018 Mar;33(3):439-446. doi: 10.1007/s00467-017-3814-1. Epub 2017 Oct 14.


Background: A 7-month-old male infant was admitted because he was suffering from nephrotic syndrome, along with encephalomyopathy, hypertrophic cardiomyopathy, clinically suspected deafness and retinitis pigmentosa, and an elevated serum lactate level.

Methods: Coenzyme Q10 supplementation was started because of the clinical suspicion of primary CoQ10 deficiency. Despite intensive efforts, he passed away 4 weeks after admission.

Results: The results of genetic tests, available postmortem, explored two hitherto undescribed mutations in the PDSS2 gene. Both were located within the polyprenyl synthetase domain. Clinical exome sequencing revealed a heterozygous missense mutation in exon 3, and our in-house joint-analysis algorithm detected a heterozygous large 2923-bp deletion that affected the 5 prime end of exon 8. Other causative defects in the CoQ10 and infantile nephrosis-related genes examined were not found. A postmortem histological, immunohistochemical, and electron microscopic evaluation of the glomeruli revealed collapsing-sclerosing lesions consistent with diffuse mesangial sclerosis. The extrarenal alterations included hypertrophic cardiomyopathy and diffuse alveolar damage. A histological evaluation of the central nervous system and skeletal muscles did not demonstrate any obvious abnormality.

Conclusions: Until now, the clinical features and the mutational status of 6 patients with a PDSS2 gene defect have been reported in the English literature. Here, we describe for the first time detailed kidney morphology features in a patient with nephrotic syndrome carrying mutations in the PDSS2 gene.

Keywords: CoQ10; Diffuse mesangial sclerosis; Nephrotic; PDSS2.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / genetics*
  • Ataxia / complications
  • Ataxia / genetics*
  • Autopsy
  • Fatal Outcome
  • Genetic Testing / methods
  • Humans
  • Infant
  • Kidney / pathology*
  • Male
  • Mitochondrial Diseases / complications
  • Mitochondrial Diseases / genetics*
  • Muscle Weakness / complications
  • Muscle Weakness / genetics*
  • Mutation
  • Nephrotic Syndrome / complications
  • Nephrotic Syndrome / etiology
  • Nephrotic Syndrome / genetics*
  • Sclerosis / complications
  • Sclerosis / genetics*
  • Ubiquinone / analogs & derivatives
  • Ubiquinone / deficiency*
  • Ubiquinone / genetics
  • Ubiquinone / therapeutic use


  • Ubiquinone
  • Alkyl and Aryl Transferases
  • prenyl diphosphate synthase, subunit 2, human
  • coenzyme Q10

Supplementary concepts

  • Coenzyme Q10 Deficiency
  • Mesangial sclerosis, diffuse