Mevalonate kinase (MK)-associated diseases encompass a broad spectrum of rare auto-inflammatory conditions, all resulting from pathogenic variants in the mevalonate kinase gene (MVK). Their clinical manifestations are highly variable, ranging from more or less serious systemic disorders, such as hereditary recurrent fevers, to purely localized pathologies such as porokeratosis. The oldest condition identified as linked to this gene is a metabolic disease called mevalonic aciduria, and the most recent is disseminated superficial actinic porokeratosis, a disease limited to the skin. The modes of inheritance of MK-associated diseases also diverge among the different subtypes: recessive for the systemic subtypes and dominant with a post-zygotic somatic genetic alteration for MVK-associated porokeratosis. This review quickly retraces the historical steps that led to the description of the various MK-associated disease phenotypes and to a better understanding of their pathophysiology, then summarizes and compares the different genetic mechanisms involved in this group of disorders, and finally discusses the diverse causes that could underlie this phenotypic heterogeneity.

甲羟戊酸激酶 (MK) 相关疾病包括广泛的罕见自身炎症性疾病，均由甲羟戊酸激酶基因 ( MVK ) 的致病变异引起。它们的临床表现差异很大，从或多或少严重的全身性疾病，如遗传性反复发热，到纯粹的局部病变，如汗孔角化症。与该基因有关的最古老的疾病是一种称为甲羟戊酸尿症的代谢疾病，而最近的一种是播散性浅表性光化性汗孔角化病，这是一种仅限于皮肤的疾病。MK 相关疾病的遗传模式在不同亚型之间也存在差异：全身亚型为隐性遗传，而MVK为合子后体细胞遗传改变显性遗传-相关的汗孔角化症。这篇综述快速追溯了导致描述各种 MK 相关疾病表型并更好地了解其病理生理学的历史步骤，然后总结和比较了这组疾病所涉及的不同遗传机制，最后讨论了不同的原因这可能是这种表型异质性的基础。