Inès Elhani1, Véronique Hentgen2, Gilles Grateau3, Sophie Georgin-Lavialle4. 1. 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. 2. Department of Pediatrics, National Reference Center for Auto-inflammatory Diseases and Amyloidosis, CEREMAIA, Versailles Hospital, Versailles, France. 3. Sorbonne University, Department of Internal Medicine, AP-HP, Hôpital Tenon, Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses Inflammatoire (CEREMAIA), Paris, France. 4. Sorbonne University, Department of Internal Medicine, AP-HP, Hôpital Tenon, Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses Inflammatoire (CEREMAIA), Paris, France. Electronic address: sophie.georgin-lavialle@aphp.fr.
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.
Authors: Simona Pisanti; Erika Rimondi; Elena Pozza; Elisabetta Melloni; Enrico Zauli; Maurizio Bifulco; Rosanna Martinelli; Annalisa Marcuzzi Journal: Int J Environ Res Public Health Date: 2022-07-25 Impact factor: 4.614