The First Report of Multicentric Carpotarsal Osteolysis Syndrome Caused by MAFB Mutation in Asian

Abstract

Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder characterized by aggressive osteolysis associated with progressive nephropathy. The early clinical presentation can mimic polyarticular juvenile idiopathic arthritis. Since 2012, MAFB mutations have been discovered in all MCTO patients. Therefore, the early diagnosis can be made based on genetic confirmation. We report the clinical manifestation of mineral bone disease and the molecular genetic study of a Thai female adolescent with MCTO. She presented with end-stage renal disease, bilateral wrist and ankle joint deformities, and subtle facial dysmorphic features. We identified a heterozygous missense MAFB mutation at nucleotide 197 from C to G (NM_005461.4; c.197C>G), predicting the change of amino acid at codon 66 from serine to cysteine (p.Ser66Cys), and the mutation was absent in the parents, indicating a de novo mutation. This report confirms the previous link between MAFB mutation and MCTO. Her unexplained hypercalcemia after a regular dose of calcium and active vitamin D supported an important role of MafB in the negative regulation of RANKL-mediated osteoclast differentiation. Therefore, we would encourage the physicians who take care of MCTO patients to closely monitor serum calcium level and perform a genetic study as a part of the management and investigation.

An unusual manifestation in a pediatric patient with MAFB mutation: Sacroiliitis in multicentric carpotarsal osteolysis syndrome

“…To date, 54 MCTO cases with MAFB mutations were reported in the literature. Most of them resembled JIA; however, treatment could not prevent disease progression and bone loss 2,4–12,14–18 . Similarly, although pain did improve with anti‐tumor necrosis factor medications in our patient, osteolysis could not be avoided.…”

“…Most of them resembled JIA; however, treatment could not prevent disease progression and bone loss. 2,[4][5][6][7][8][9][10][11][12][14][15][16][17][18] Similarly, although pain did improve with anti-tumor necrosis factor medications in our patient, osteolysis could not be avoided. The main problem in MCTO was suggested to be increased RANKL activation and excessive osteoclastic activity, but the cause of the selection of distinctive bones remains unclear.…”

Multicentric Carpo-Tarsal Osteolysis Syndrome Mimicking Juvenile Idiopathic Arthritis: Two Case Reports and Review of the Literature

“…Bio-DMARDs (e.g., etanercept, infliximab, adalimumab, tocilizumab, and abatacept) are not reported to slow down osteolysis progression appreciably, although etanercept, infliximab, and tocilizumab are reported to relieve pain (7,16). Other drug treatments, such as calcium supplements, should be taken with caution since one patient developed a hypercalcemia-induced convulsive episode during treatment (21). For patients with severe bone damage, surgical treatment is necessary.…”

Multicentric Carpotarsal Osteolysis Syndrome in a Mother and Daughter with a <b><i>MAFB</i></b> Missense Variant and Natural History of the Disease

“…MCTO has autosomal dominant inheritance with heterozygous mutation in the MAFB gene (v-maf musculoaponeurotic fibrosarcoma oncogene ortholog B; MIM #608968). We found 11 studies in the literature reporting 18 different heterozygous MCTO-related missense MAFB variants (49 patients) [Zankl et al, 2012;Dworschak et al, 2013;Mehawej et al, 2013;Mumm et al, 2014;Sun et al, 2016;Zhuang et al, 2017;Choochuen et al, 2018;Park et al, 2018;Stajkovska et al, 2018;Upadia et al, 2018;Li et al, 2020]. All these variants are mapped in a small region of 52 base pairs in the transcription factor amino-terminal transactivation domain.…”