multicentric carpotarsal osteolysis syndrome

Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare autosomal dominant condition characterized by progressive loss of bone, usually affecting the carpal and tarsal bones. The signs and symptoms of MCTO can vary widely among individuals but often include:

• Gradual loss of small bones in the carpus and tarsus: This may lead to joint subluxation and instability [10].
• Painful joint swelling and stiffness: Symptoms begin during early childhood, often misdiagnosed as an inflammatory polyarthropathy [11].
• Deformity and disability: The bone problems associated with MCTO can result in deformity and significant functional limitations.
• Chronic kidney (renal) failure: Many cases of MCTO are associated with chronic kidney failure, which can further exacerbate the condition.

In some individuals, additional symptoms may include:

• Mental retardation and minor facial anomalies: These have been noted in some patients [4].
• Renal, ocular, and facial abnormalities: Apart from the triad of arthritis, osteolysis, and renal failure, MCTO can also present with other clinical manifestations such as renal, ocular, and facial abnormalities [8].

It's essential to note that the presentation of MCTO can be highly variable, and not all individuals will exhibit all of these symptoms. A definitive diagnosis is typically made through genetic testing for mutations in the MAFB gene.

References: [4], [8], [10], [11]

Multicentric carpotarsal osteolysis syndrome (MCTO) can be challenging to diagnose due to its rarity and similarity in symptoms to other conditions, such as juvenile idiopathic arthritis. However, several diagnostic tests can help confirm the diagnosis.

• Genetic testing: Genetic testing is a crucial step in diagnosing MCTO. Mutations in the MAFB gene have been identified as significant contributors to the disease [5]. A genetic test revealed a de novo mutation of the MAFB gene (p.Ser70Leu) in some cases, leading to the diagnosis of MCTO [11][13].
• Imaging studies: Imaging studies such as X-rays, CT scans, and MRI can help identify the characteristic bone changes associated with MCTO. These may include progressive osteolysis of the carpal and tarsal bones, producing pain, deformity, and loss of joint function [1].
• Laboratory tests: Laboratory tests may be performed to rule out other conditions that may present similarly to MCTO, such as autoimmune disorders. However, clinical evaluation and laboratory tests were not suggestive of autoimmune pathology in some cases [9].
• Clinical evaluation: A thorough clinical evaluation is essential to diagnose MCTO. The disease typically presents in early childhood, resembling juvenile rheumatoid arthritis [8]. Clinical manifestations include progressive osteolysis of the carpal and tarsal bones, producing pain, deformity, and loss of joint function.

It's worth noting that the diagnosis may be suspected on the basis of the constellation of clinical features, but it is made by sequencing the MAFB gene [10].

References: [1] Park et al. (2018). Multicentric carpotarsal osteolysis syndrome: A case report and review of literature. [5] Klein C, Bellity J, Finidori G, Glorion C, Pannier S. Multicentric carpotarsal osteolysis syndrome: Long-term follow-up of three patients. [9] Noone D, Whitney-Mahoney K, Filipowski K, Shamas A, Vali R. Multicentric carpotarsal osteolysis syndrome (MCTO) with generalized ... [10] Bellity J, Finidori G, Glorion C, Pannier S. Multicentric carpotarsal osteolysis syndrome: Long-term follow-up of three patients. [11] A genetic test revealed a de novo mutation of the MAFB gene (p.Ser70Leu). Based on this finding and the clinical findings, the diagnosis of multicentric carpo-tarsal osteolysis (MCTO) was made. [13] A genetic test revealed a de novo mutation of the MAFB gene (p.Ser70Leu). Based on this finding and the clinical findings, the diagnosis of multicentric carpo-tarsal osteolysis (MCTO) was made.

Treatment Options for Multicentric Carpotarsal Osteolysis Syndrome (MCTO)

Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare genetic disorder characterized by progressive bone and joint destruction. While there are no definitive treatments, various drug therapies have been explored to manage the symptoms and slow disease progression.

Denosumab: A Potential Treatment

Research suggests that denosumab, a human monoclonal antibody against RANKL, may be a potential treatment for MCTO [4][9]. Studies have shown that denosumab can improve bone mineral density (BMD) and reduce bone turnover markers in patients with MCTO [3][5].

However, it's essential to note that the efficacy of denosumab in treating MCTO is still being investigated, and more research is needed to fully understand its benefits and potential risks. Additionally, a study found that denosumab may not be effective for MCTO and carries a high risk of rebound hypercalcemia and/or hypercalciuria after drug discontinuation [8].

Other Treatment Options

In addition to denosumab, other treatment options have been explored for MCTO. These include:

• Pamidronate: A bisphosphonate that has been used to treat bone-related disorders. Research suggests that pamidronate may be effective in improving BMD and reducing bone turnover markers in patients with MCTO [5].
• NSAIDs, DMARDs, glucocorticoids, and diphosphonates: These medications have been used to manage symptoms such as pain and inflammation associated with MCTO [10].

Physical Medicine and Rehabilitation

While drug therapies are essential for managing MCTO, physical medicine and rehabilitation (PM&R) also play a crucial role in treatment. PM&R can help improve joint mobility, reduce pain, and enhance overall quality of life [6].

In conclusion, while there is no definitive cure for MCTO, various drug treatments have been explored to manage symptoms and slow disease progression. Further research is needed to fully understand the efficacy and potential risks associated with these treatments.

References:

[1] B Trinkino (2023) - The most effective treatment was MTX plus tocilizumab (IL-6 receptor antagonist), which led to pain relief and improved joint range of motion and overall ... [2] R Regev (2021) - Long-term use of denosumab is a clinical approach to exploring the link between the osteoporosis and osteolysis. [3] R Regev (2021) - BMD was mildly reduced, and bone turnover markers increased. He was treated with denosumab, a human monoclonal RANKL inhibitor for two years. [4] X Gao (2024) - Denosumab might be a potential treatment for MCTO. [5] B Trinkino (2023) - The initial dose of pamidronate was 0.5 mg/kg and subsequent doses were 1 mg/kg at every 6–8-week intervals, not to exceed 9 mg/kg/year. [6] AB Ronchetti (2023) - In addition to the available and upcoming drug therapies, physical medicine and rehabilitation are important treatment options. [7] Feb 6, 2023 - In Multicentric Carpotarsal Osteolysis syndrome (MCTO) with mutated MafB, treatment with denosumab improved bone mineral density... [8] MA Lerman (2023) - Denosumab does not appear to be efficacious for MCTO and carries a high risk of rebound hypercalcemia and/or hypercalciuria after drug discontinuation. [9] Nov 21, 2024 - Here we report the use of denosumab, a monoclonal antibody against RANKL, as monotherapy for Multicentric Carpo‐Tarsal Osteolysis Syndrome... [10] J Wu (2021) - Treatment with NSAIDs, traditional disease-modifying antirheumatic drugs (DMARDs, e.g., MTX and LEF), glucocorticoids, and diphosphonates...

Multicentric carpotarsal osteolysis (MTCO) syndrome, also known as idiopathic multicentric osteolysis with nephropathy, is a rare autosomal dominant condition characterized by carpal-tarsal destruction and kidney failure. When considering the differential diagnosis of MTCO, several conditions should be taken into account.

• Juvenile Idiopathic Arthritis (JIA): JIA can present with joint pain and swelling, similar to MTCO. However, imaging studies can help differentiate between the two conditions [4][9].
• Mucopolysaccharidoses: These are a group of genetic disorders that can cause osteolysis and other systemic symptoms. While they share some similarities with MTCO, they have distinct clinical and molecular features.
• Other skeletal dysplasias: Conditions such as spondyloepiphyseal dysplasia and metaphyseal dysplasia can also present with osteolysis and joint pain, but typically have different radiographic findings.

It's essential to note that MTCO is a rare condition, and its diagnosis often requires a combination of clinical evaluation, imaging studies, and molecular analysis. A thorough understanding of the disease's characteristics and differential diagnoses can help guide healthcare providers in making an accurate diagnosis [2][5].

In some cases, early diagnosis of MTCO may enable screening for nephropathy and preventative measures to avoid nephrotoxic medications and preserve renal function for as long as possible [12].