Further phenotypic heterogeneity of CoQ10 deficiency associated with steroid resistant nephrotic syndrome and novel COQ2 and COQ6 variants

β‐ RA reduces DMQ /CoQ ratio and rescues the encephalopathic phenotype in Coq9 R239X mice

“…Therefore, β‐RA should be preferentially considered for the treatment of human CoQ 10 deficiency with accumulation of DMQ 10 , as it has been reported in patients with mutations in COQ9 , COQ7, or COQ4 (Duncan et al , ; Freyer et al , ; Danhauser et al , ; Herebian et al , 2017b; Wang et al , ; Smith et al , ) but also in cells under siRNA knockdown of COQ3 , COQ5 and COQ6 (Herebian et al , 2017b). Similar principles could be applied for 3,4‐hydroxybenzoic acid, vanillic acid, 2‐methyl‐4‐hydroxybenzoic acid, or 2,3‐dimethoxy‐4‐hydroxybenzoic acid in the cases of mutations in COQ6, COQ5, or COQ3 (Heeringa et al , ; Yoo et al , ; Ribas et al , ; Gigante et al , ; Herebian et al , ; Pierrel, ), respectively. Furthermore, 4‐HB analogs may provide therapeutic effects in other conditions, e.g., mitochondrial disorders, since secondary CoQ deficiency due to decreased levels of CoQ biosynthetic proteins have been recently reported in various mouse models of mitochondrial diseases (Kuhl et al , ); or metabolic diseases due to insulin resistance since secondary CoQ deficiency due to decreased levels of CoQ biosynthetic proteins have been recently described in in vitro insulin resistance models and adipose tissue from insulin‐resistant humans (Fazakerley et al , ).…”

Mutations in COQ8B (ADCK4) found in patients with steroid-resistant nephrotic syndrome alter COQ8B function

“…Growth minimum medium SM Glu (2% glucose, 0.17% yeast nitrogen base without amino acids, 0.5% ammonium sulfate, histidine 10 mg/l, leucine 60 mg/l, tryptophan 20 mg/l) was supplemented with amino acids in order to cover the yeast auxotrophies except for uracil. For mitochondrial purification (for Western blot and biochemical analyses), 0.1% of glucose was added to YPGly medium (1% yeast extract, 2% peptone, and 3% glycerol) in order to allow growth of null mutants(Gigante et al., ). When necessary, 500 μg/ml of doxycyclin was added to the YPGly medium.…”

CoQ10-related sustained remission of proteinuria in a child with COQ6 glomerulopathy—a case report

“…These include patients with mutations in COQ2 , COQ6 , PDSS2 and COQ8B . A few families with COQ6 mutations with multiple organ involvement were described in which coenzyme Q10 (CoQ10) therapy was successfully carried out [4, 5] (Table 1). We present the case of steroid resistant glomerulopathy due to a COQ6 defect with no additional systemic symptoms, which responded to oral CoQ10 treatment.…”

“…Gly255Arg2 moproteinuriaTurkeyNDA2 moCoQ10: 15 mg/kg/d → 30 mg/kg/d after 2 months of treatmentACE-I: 1.25 mg/d–uPCR:40 mg/mg → 8 mg/mg (after 2 mo) → 5.8 mg/mg → 4.8 mg/mg (15 mo) → 0.55 mg/mg (4.5 y. )–Normal renal functionAsymptomatic at the onsetSND (10 mo)Bilateralnephrolithiasis (5 mo)GR (10 mo)[4]c.782C > T7 (hom)p.Pro261Leu8 moSRNSItalyMPGNNDACoQ10 – to prevent neurological symptoms; dose – NDA–ESRD at 20 mo–Lack of neurological symptomsNone[5]c.1058C > A9 (hom)p.Ala353Asp2.5 yrSRNSTurkeyFSGS5.5 yCoQ10 –dose: NDACsA – dose:NDA24 h protein in urine: 7 mg/m2/h → 3.7 mg/m2/h (after 2 mo) → full remission–No hearing improvement–Relapse of proteinuria 57 mg/m2/h after cessation of CoQ10SND[4, 6]c.1078C > T9 (hom)p. Arg360Trp10 monephrotic proteinuriaChinaNDANDACoQ10 – dose: 30 mg/kg–uPCR 7.2 mg/mg → 1.3 mg/mg (after 2 mo) → 0.01 mg/mg (after 3 mo)–Improvement of growth retardation–SND (2 yr)Cardiovascular abnormalityMotor and mental retardationUnilateral ptosis[7]

SRNS steroid resistant nephrotic syndrome, FSGS focal segmental glomerulosclerosis , MPGN membranoproliferative glomerulonephrirts, CoQ10 coenzyme Q10, ACE-I angiotensin-converting-enzyme inhibitors, CsA cyclosporine A , SND sensorineural deafness, ESRD end-stage renal disease, uPCR urine protein-creatine ratio, GR growth retardation, NDA no data available, hom homozygous in affected individual

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