Division of Hematology-Oncology, Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA.
Pediatrics. 2010 Apr;125(4):e964-8. doi: 10.1542/peds.2009-1774. Epub 2010 Mar 1.
Mevalonate kinase deficiency (MKD) is a rare inborn error of metabolism caused by mutations in the mevalonate kinase (MVK) gene. The clinical phenotype is variable, ranging from the hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) to mevalonic aciduria (MA), a severe metabolic disease. We report here for the first time (to our knowledge) the case of a patient with MKD and congenital dyserythropoietic anemia. Clinical and laboratory characteristics of inflammatory attacks were compatible with HIDS, but mild dysmorphic features and elevated urinary mevalonic acid levels in the absence of an inflammatory attack suggested an intermediate phenotype between HIDS and MA. Genomic sequencing of the MVK gene revealed compound heterozygosity for a missense mutation previously described in MA (V310M) and a novel missense mutation (Y116H). By contrast, sequencing of the novel CDAII (SEC23B) gene revealed no mutations, suggesting that the bone marrow abnormalities were causally related to the MKD. Treatment with corticosteroids and colchicine directed at controlling the autoinflammatory disease resulted in improvement of the anemia.
甲羟戊酸激酶缺乏症（MKD）是一种由甲羟戊酸激酶（MVK）基因突变引起的罕见先天性代谢缺陷病。其临床表现具有多样性，从高免疫球蛋白 D 和周期性发热综合征（HIDS）到严重的代谢疾病甲羟戊酸尿症（MA）均有涉及。在此，我们首次（据我们所知）报告了一例 MKD 合并先天性红细胞生成异常性贫血患者。炎症发作时的临床和实验室特征与 HIDS 相符，但存在轻微的畸形特征，且在无炎症发作时尿甲羟戊酸水平升高，提示其表型处于 HIDS 和 MA 之间。MVK 基因的基因组测序显示，存在先前报道的与 MA 相关的错义突变（V310M）和一种新型错义突变（Y116H）的复合杂合性。相比之下，新型 CDAII（SEC23B）基因的测序未发现突变，提示骨髓异常与 MKD 存在因果关系。针对自身炎症性疾病的皮质类固醇和秋水仙碱治疗改善了贫血。
