Table 3 Differential diagnosis of GSD

GLA

GLA is characterized by multifocal lymphatic malformations involving bones, viscera, and soft tissues. The osteolytic lesions are confined to the medullary cavity and are relatively stable.

KLA

KLA can cause thrombocytopenia syndrome and coagulation dysfunction, and spindle-shaped “Kaposi-like” endothelial cells can be observed via histological biopsy.

Osteomyelitis

Patients have elevated ESR and CRP. Biopsy and bacterial culture of lesion tissue can help identify the infecting microorganisms.

Skeletal tuberculosis

Patients may have symptoms such as low fever and night sweats, and may also have pulmonary tuberculosis. They generally have a history of tuberculosis infection/contact, and tuberculin tests and tuberculosis cultures are usually positive.

Rheumatoid arthritis

Patients will experience morning stiffness. RF, ACPA, CRP or ESR are generally elevated, and X-rays can reveal characteristic joint changes.

Multiple myeloma

Typical symptoms of multiple myeloma are hypercalcemia, renal failure, anemia, and bone pain. M-protein is elevated in patients, and bone marrow biopsy may reveal clonal plasma cells or plasma cell tumors.

Langerhans cell histiocytosis

Langerhans cell histiocytosis may present with fever, rash, lymphadenopathy, etc. Pathological biopsy shows well-differentiated histiocytic proliferation, with positive CD68, CD1a, S100, and CD207. Birbeck granules can be observed.

Metastatic bone tumors

Patients have primary tumor lesions. PET-CT, tumor markers and pathological biopsy can assist in diagnosis.

Fibrous dysplasia

X-rays show fibrous dysplasia as ground-glass, and blood tests may show elevated ALP. Some patients have GNAS mutations.

Hyperparathyroidism

The patient’s serum calcium and PTH are elevated, and parathyroid adenoma can be detected in most patients. In rare cases, a complication called brown tumor may occur.

Paget’s disease

Blood tests may show elevated ALP. Some patients have SQSTM1 and RANK mutations.

MCTO

It is characterised by carpal-tarsal destruction and kidney failure. The disease results from mutations in the MAFB gene.

MONA

The bone abnormalities begin in the hands and feet and then spread to other parts of the body, with many patients developing subcutaneous nodules. The disease results from mutations in the MMP2 gene.

Winchester syndrome

The clinical presentation is similar to MONA, but without subcutaneous nodules. The disease results from mutations in the MMP14 gene.

Hajdu-Cheney syndrome

Hajdu-Cheney syndrome causes problems with the patient’s connective tissue, which can result in growth retardation, hearing loss, osteopenia, and hirsutism. The disease results from mutations in the NOTCH2 gene.