Three cases of multicentric carpotarsal osteolysis syndrome: a case series

Abstract

BackgroundMulticentric carpotarsal osteolysis syndrome (MCTO) is characterized by progressive destruction and disappearance of the carpal and tarsal bones associated with nephropathy. MCTO is caused by loss-of-function mutations in the MAF bZIP transcription factor B (MAFB) gene.Case presentationThis report describes three unrelated patients with MAFB mutations, including two male and one female patient. Osteolytic lesions in the carpal and tarsal bones were detected at 2 years, 12 years, and 14 months of age, respectively. Associated proteinuria was noted at 4 years, 12 years, and 3 months of age, respectively. Kidney biopsy was performed in two of them and revealed focal segmental glomerulosclerosis (FSGS). One patient showed progression to end-stage renal disease, that is by 1 year after the detection of proteinuria. The second patient had persistent proteinuria but maintained normal renal function. In the third patient, who did not undergo a kidney biopsy, the proteinuria disappeared spontaneously. The bony lesions worsened progressively in all three patients. Mutational study of MAFB revealed three different mutations, two novel mutations [c.183C > A (p.Ser61Arg) and c.211C > G (p.Pro71Ala)] and one known mutation [c.212C > T (p.Pro71Leu)].ConclusionWe report three cases with MCTO and two novel MAFB mutations. The renal phenotypes were different among the three patients, whereas progressive worsening of the bony lesions was common in all patients. We also confirmed FSGS to be an early renal pathologic finding in two cases. A diagnosis of MCTO should be considered in patients with progressive bone loss concentrated primarily in the carpal and tarsal bones and kidney involvement, such as proteinuria.

Multicentric carpotarsal osteolysis syndrome (MCTO) with generalized high bone turnover and high serum RANKL: Response to denosumab

“…The goals of these therapies have been to arrest progression of the carpal and tarsal osteolysis. In particular, the efficacy of bisphosphonates has been questioned ( Park et al, 2018 ; Carmichael et al, 2007 ). Furthermore, bisphosphonates are potentially nephrotoxic ( Domschke and Schuetz, 2014 ), which raises an additional concern in the context of a condition in which renal failure is an outcome.…”

“…Multicentric Carpotarsal Osteolysis Syndrome (MCTO) (OMIM Entry #166300) is a rare skeletal disorder characterized by progressive osteolysis of the carpal and tarsal bones, and nephropathy ( Park et al, 2018 ). Clinical manifestations include progressive osteolysis of the carpal and tarsal bones producing pain, deformity and loss of joint function.…”

“…Craniofacial anomalies and mental impairment have also been observed including triangular shaped face, protruding eyes, and micrognathia ( Carnevale et al, 1987 ). There are suggestions in the literature that this disorder may be related to Gorham Stout Disease ( Park et al, 2018 ). MCTO patients are most often followed by rheumatologists since the presentation mimics juvenile idiopathic arthritis and is often treated with glucocorticoids and anti-inflammatory agents.…”

Zebrafish mafbb Mutants Display Osteoclast Over-Activation and Bone Deformity Resembling Osteolysis in MCTO Patients

“…MCTO individuals carry heterozygous missense mutations in MAFB with a dominant-inheritance pattern [ 14 , 15 , 16 ]. Whether the mutation in MCTO is haploinsufficiency or a dominant negative effect remains unclear.…”

“…Mutations in MAFB have been reported to be responsible for the multicentric carpotarsal osteolysis syndrome (MCTO) [ 14 , 15 , 16 ]. MCTO is a rare skeletal and nephropathic disorder, and the responsible mutations are all missense mutations in the amino-terminal transactivation domain of MAFB.…”