Peciuliene Skaiste, Burnyte Birute, Gudaitiene Rymanta, Rusoniene Skirmante, Drazdiene Nijole, Liubsys Arunas, Utkus Algirdas
Neonatology Centre of Vilnius University, Santariškių St. 7, Vilnius, Lithuania.
Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
Pediatr Rheumatol Online J. 2016 Mar 25;14(1):19. doi: 10.1186/s12969-016-0081-9.
Mevalonate kinase deficiency is a metabolic autoinflammatory syndrome caused by mutations in the MVK gene, mevalonate kinase, the key enzyme in the non-sterol isoprenoid biosynthesis pathway. Two phenotypes of mevalonate kinase deficiency are known based on the level of enzymatic deficiency, mevalonic aciduria and hyperimmunoglobulinemia D syndrome, but a wide spectrum of intermediate phenotypes has been reported. Currently one of the most effective treatments is biological therapy (with interleukin-1 antagonist anakinra or tumour necrosis factor-α inhibitor etanercept).
The patient in this case has a phenotype contributing to a severe disease that caused the symptoms to manifest very early, in the prenatal period. Mevalonate kinase deficiency was suspected on the basis of clinical (hydrops fetalis, hepatosplenomegaly, hypotonia) and laboratory signs (anaemia, intense acute phase reaction, increased urinary excretion of mevalonic acid). Mutation analysis of the MVK gene confirmed the biochemical diagnosis. Treatment with the interleukin-1 antagonist anakinra was started (minimal dose of 1 mg/kg/day) and revealed its efficacy after three days.
Our case highlights the need for a very detailed clinical and laboratory assessment in new-borns with any suggestion of autoinflammatory disorders. It is important that patients are diagnosed as early as possible to provide better multidisciplinary follow-up and therapy when needed.
甲羟戊酸激酶缺乏症是一种代谢性自身炎症综合征，由MVK基因（甲羟戊酸激酶，非甾醇类异戊二烯生物合成途径中的关键酶）突变引起。根据酶缺乏水平，已知甲羟戊酸激酶缺乏症有两种表型，即甲羟戊酸尿症和高免疫球蛋白D综合征，但也有广泛的中间表型报道。目前最有效的治疗方法之一是生物治疗（使用白细胞介素-1拮抗剂阿那白滞素或肿瘤坏死因子-α抑制剂依那西普）。
本病例中的患者具有导致严重疾病的表型，致使症状在产前极早期就已显现。基于临床症状（胎儿水肿、肝脾肿大、肌张力减退）和实验室检查结果（贫血、强烈的急性期反应、甲羟戊酸尿排泄增加）怀疑为甲羟戊酸激酶缺乏症。MVK基因的突变分析证实了生化诊断。开始使用白细胞介素-1拮抗剂阿那白滞素进行治疗（最小剂量为1毫克/千克/天），三天后显示出疗效。
我们的病例强调了对有任何自身炎症性疾病迹象的新生儿进行非常详细的临床和实验室评估的必要性。尽早诊断患者很重要，以便在需要时提供更好的多学科随访和治疗。
