Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, South Korea.
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, South Korea.
Front Immunol. 2021 Dec 7;12:782780. doi: 10.3389/fimmu.2021.782780. eCollection 2021.
Mevalonic aciduria (MA) is the most severe clinical subtype of mevalonate kinase deficiency (MKD) caused by an inherited defect in the mevalonate pathway. The treatment of MKD focuses on the suppression of recurrent hyperinflammatory attacks using anti-inflammatory drugs. Recently, allogeneic hematopoietic stem cell transplantation (HCT) was shown to successfully ameliorate autoinflammatory attacks in patients with MKD. Here, we report a case of an infant who showed severe recurrent systemic inflammation and was diagnosed with MA. Although she responded to steroids, her symptoms relapsed after the dose was tapered, and organ deterioration occurred. Therefore, at the age of 11 months, HCT from a matched, unrelated donor was performed for curative treatment. However, at 50 days after transplantation, acute myeloid leukemia was diagnosed, which was chemo-refractory. A second HCT from her haploidentical father was performed to treat the acute myeloid leukemia, but the patient died of sepsis on day 4 after transplantation. This is the first report of malignancy following HCT for MA. Our findings suggest that normalizing the mevalonate pathway after HCT in patients with MKD impacts patients differently depending on the clinical spectrum and severity of disease.
戊二酸血症 I 型（MA）是由于甲羟戊酸途径遗传缺陷引起的甲羟戊酸激酶缺乏症（MKD）最严重的临床亚型。MKD 的治疗重点是使用抗炎药抑制复发性炎症过度活跃。最近，异体造血干细胞移植（HCT）已被证明可成功改善 MKD 患者的自身炎症攻击。在此，我们报告了一例患有 MA 的婴儿，她表现出严重的复发性全身炎症。尽管她对类固醇有反应，但在减少剂量后症状复发，并且器官恶化。因此，在 11 个月大时，进行了来自匹配的、无关供体的 HCT 进行治愈性治疗。然而，在移植后 50 天，诊断出急性髓系白血病，且对化疗有抗性。为了治疗急性髓系白血病，进行了第二次来自她单倍体父亲的 HCT，但患者在移植后第 4 天死于败血症。这是首例报道 MA 患者接受 HCT 后发生恶性肿瘤的病例。我们的研究结果表明，在 MKD 患者中，HCT 后甲羟戊酸途径的正常化会根据疾病的临床谱和严重程度对患者产生不同的影响。
