# Association Between Vitamin D, Vitamin B12 and Folate Levels and Persistent Subclinical Inflammation in Pediatric Familial Mediterranean Fever

## TL;DR

This study investigated whether vitamin D, B12, and folate levels are linked to subclinical inflammation in children with Familial Mediterranean Fever but found no significant association.

## Contribution

The study is the first to explore the relationship between these micronutrients and subclinical inflammation in pediatric FMF patients.

## Key findings

- Persistent subclinical inflammation was observed in 12.3% of pediatric FMF patients.
- No significant differences in vitamin D, B12, or folate levels were found between patients with and without subclinical inflammation.
- Homozygous M694V mutations were present in 28% of the patients.

## Abstract

Background/Objectives: Familial Mediterranean fever (FMF) is the most common periodic fever syndrome worldwide, and persistent subclinical inflammation has been reported in 10–20% of cases during attack-free periods. Although the immunomodulatory effects of vitamin D, vitamin B12 and folate have been investigated in various conditions, data on their relationship with subclinical inflammation in FMF patients remain limited. This study aimed to evaluate the association between micronutrient levels and subclinical inflammation in pediatric FMF. Methods: Children aged 2–18 years with an FMF diagnosis of more than two years, receiving regular colchicine therapy, and attack-free for at least two months were included. Patients with other autoinflammatory diseases, colchicine resistance, concomitant renal disease, active infection, or inadequate follow-up were excluded. Demographic, clinical, genetic, and biochemical data were analyzed. Results: A total of 253 patients were included, with a median age of 14 years (range, 3–18), and 133 (52.6%) were female. Persistent subclinical inflammation was observed in 31 patients (12.3%). Genetic analysis revealed homozygous M694V mutations in 71 patients (28%). Median vitamin levels were as follows: vitamin D 17.3 ng/mL (IQR 10.6–27.1), vitamin B12 288 pg/mL (IQR 214–367), and folate 6.4 ng/mL (IQR 4.8–7.6). Comparison between patients with and without subclinical inflammation showed no significant differences in micronutrient levels. Conclusions: Although micronutrients have been reported to play immunomodulatory roles, we did not observe significant association between vitamin levels and subclinical inflammation in pediatric FMF patients in our study.