{'fraction_non_alphanumeric': 0.030553787396562698, 'fraction_numerical': 0.022278803309993635, 'mean_word_length': 5.298597194388778, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 1, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Successful maintenance of partial remission in a child with COQ2 nephropathy by coenzyme Q10 treatment

Steroid-resistant nephrotic syndrome is a rare kidney disease characterized by nephrotic proteinuria, hypoalbuminaemia, oedemas and dyslipidaemia. Searching for genetic forms of the disease among a cohort of 74 Czech and Slovak children, we identified siblings carrying a previously published homozygous causative variant in the COQ2 gene (c.683A>G, p. Asn228Ser). The COQ2 encodes parahydroxybenzoidpolyprenyltransferase necessary for the synthesis of coenzyme Q10 (CoQ10). The phenotypic range associated with biallelic pathogenic variants in this gene includes, but is not limited to, COQ2 nephropathy with CoQ10 deficiency, whose effective treatment with oral CoQ10 substitution was recently reported. Here we describe further case of such successful substitution therapy. The index patient, a girl, manifested with nephrotic syndrome (NS) at 1 year of age without extrarenal features. Her 6-year-old sister had manifested with steroid-resistant nephrotic syndrome and had progressed rapidly to end stage renal disease 3 years before the index patient was diagnosed. No history of NS was noted elsewhere in the family. The index patient presented with an accidental finding of nephrotic proteinuria after acute gastroenteritis. Her growth and psychomotoric development were normal. Her initial laboratory results showed normal renal function (GFR: 123 mL/min/1.73m), hypoalbuminaemia (32 g/L) and nephrotic proteinuria (3.25 g/m/day). Renal biopsy revealed focal segmental glomerulosclerosis in both siblings. The therapy (Fig. 1) started with the initial 6-weeks course of prednison (60 mg/m/day) and 1 month of low dose ramipril therapy (0.625 mg/day) discontinued early because of symptomatic hypotension without any improvement; after 5 months with gradual reduction in prednison dose, cyclosporine A was added and proteinuria significantly decreased from 1.79 to 0.52 g/m/day. At this time point, genetic diagnosis of the siblings was established. Based on literature data, her combined therapy (cyclosporine A + prednison) was immediately switched to monotherapy with CoQ10 dosed at 15 mg/kg/day. The achieved partial remission was maintained on this monotherapy, with further gradual reduction in proteinuria (Fig. 1). Although this result cannot prove a direct causative role of CoQ10 in the remission and we cannot associate the sustained remission solely to treatment with CoQ10, indirect indications of its efficacy include the length of the remission (approximately 2 years), the continuing decrease in proteinuria, and the stark contrast to the clinical course in her older sister who – while on combined immunosuppression – rapidly progressed to end stage renal disease. In conclusion, this case report renders further support to the notion of reversibility of COQ2 nephropathy by a timely substitution of this essential mitochondrial quinone. We thank Andrea Klabníková for the help with the preparation of the manuscript. The study was supported by the Ministry of Health of the Czech Republic, grant number 15-31586A.