Department of Pediatrics, Division of Nephrology, Seattle Children's Hospital and University of Washington, 4800 Sand Point Way NE, OC.9.830, Seattle, WA, 98105, USA.
Department of Medical Genetics, University of Washington Medical Center, Seattle, WA, USA.
Pediatr Nephrol. 2018 Jul;33(7):1257-1261. doi: 10.1007/s00467-018-3937-z. Epub 2018 Apr 10.
Nephrotic syndrome can be caused by a subgroup of mitochondrial diseases classified as primary coenzyme Q (CoQ) deficiency. Pathogenic COQ2 variants are a cause of primary CoQ deficiency and present with phenotypes ranging from isolated nephrotic syndrome to fatal multisystem disease.
CASE-DIAGNOSIS/TREATMENT: We report three pediatric patients with COQ2 variants presenting with nephrotic syndrome. Two of these patients had normal leukocyte CoQ levels prior to treatment. Pathologic findings varied from mesangial sclerosis to focal segmental glomerulosclerosis, with all patients having abnormal appearing mitochondria on kidney biopsy. In two of the three patients treated with CoQ supplementation, the nephrotic syndrome resolved; and at follow-up, both have normal renal function and stable proteinuria.
COQ2 nephropathy should be suspected in patients presenting with nephrotic syndrome, although less common than disease due to mutations in NPHS1, NPHS2, and WT1. The index of suspicion should remain high, and we suggest that providers consider genetic evaluation even in patients with normal leukocyte CoQ levels, as levels may be within normal range even with significant clinical disease. Early molecular diagnosis and specific treatment are essential in the management of this severe yet treatable condition.
肾病综合征可由归类为原发性辅酶 Q（CoQ）缺乏症的亚组线粒体疾病引起。致病性 COQ2 变体是原发性 CoQ 缺乏症的病因，表现为从孤立性肾病综合征到致命多系统疾病的各种表型。
病例诊断/治疗：我们报告了三例 COQ2 变体导致肾病综合征的儿科患者。这两例患者在治疗前白细胞 CoQ 水平正常。病理发现从系膜硬化到局灶节段性肾小球硬化不等，所有患者肾活检均显示线粒体异常。在接受 CoQ 补充治疗的三例患者中的两例中，肾病综合征得到缓解；随访时，两者肾功能均正常，蛋白尿稳定。
尽管 COQ2 肾病比由 NPHS1、NPHS2 和 WT1 突变引起的疾病少见，但对于出现肾病综合征的患者，应怀疑 COQ2 肾病。怀疑指数应保持较高，我们建议即使在白细胞 CoQ 水平正常的患者中，也应考虑进行基因评估，因为即使存在严重的临床疾病，CoQ 水平也可能在正常范围内。早期的分子诊断和特定的治疗对于这种严重但可治疗的疾病的管理至关重要。
