Sorbonne University, Department of Internal Medicine, AP-HP, Hôpital Tenon, Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses Inflammatoire (CEREMAIA), Paris, France; Department of Pediatrics, National Reference Center for Auto-inflammatory Diseases and Amyloidosis, CEREMAIA, Versailles Hospital, Versailles, France.
Department of Pediatrics, National Reference Center for Auto-inflammatory Diseases and Amyloidosis, CEREMAIA, Versailles Hospital, Versailles, France.
Mol Genet Metab. 2022 Jun;136(2):85-93. doi: 10.1016/j.ymgme.2022.04.006. Epub 2022 Apr 30.
Mevalonate kinase deficiency (MKD) is a monogenic auto-inflammatory disease. Its manifestations range from partial MKD to mevalonic aciduria (MVA). All patients display a periodic fever, and MVA patients additionally exhibit severe neurological involvement. The objective of this work was to describe neurological manifestations of MKD.
A systematic literature review was performed from January 1990 to January 2022. Forty-five patients from 18 case reports and five cohort studies were included in the analysis.
In cohort studies, the most-reported manifestations were headaches (41%) and fatigue (31%). Serious involvements including ataxia and developmental delay were described less than 1% of patients but 22-31% of case reports. They consistently appeared in the first years of life. Retinal dystrophy was frequently reported (31%) in case reports. Other manifestations, including uveitis, aseptic meningitis, and stroke remained rare.
Severe neurological manifestations are rare in MKD but are responsible for major functional disabilities. They are present at onset and never appear at follow-up of patients with mild MKD. Conversely, headaches and fatigue are frequent symptoms that should be investigated. Visual examinations should be performed on the appearance of visual symptoms. The efficacy of anti-IL-1β therapy on neurological manifestations should be further investigated.
甲羟戊酸激酶缺乏症（MKD）是一种单基因自身炎症性疾病。其表现范围从部分 MKD 到甲羟戊酸尿症（MVA）。所有患者均表现为周期性发热，MVA 患者还伴有严重的神经受累。本研究旨在描述 MKD 的神经表现。
对 1990 年 1 月至 2022 年 1 月的文献进行了系统回顾。分析了来自 18 例病例报告和 5 项队列研究的 45 例患者。
在队列研究中，最常报告的表现是头痛（41%）和疲劳（31%）。严重的表现包括共济失调和发育迟缓，在不到 1%的患者中描述，但在 22%-31%的病例报告中描述。这些表现均出现在生命的最初几年。视网膜营养不良在病例报告中经常报道（31%）。其他表现，包括葡萄膜炎、无菌性脑膜炎和中风仍然很少见。
MKD 中严重的神经表现罕见，但会导致严重的功能障碍。它们在发病时出现，在轻度 MKD 患者的随访中从未出现。相反，头痛和疲劳是常见的症状，应进行调查。出现视觉症状时应进行视觉检查。抗 IL-1β 治疗对神经表现的疗效应进一步研究。
