Neurological manifestations in mevalonate kinase deficiency: A systematic review.

Abstract

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.