Choreoathetosis: A Rare Manifestation of Hyper-IgM Syndrome (CD40 ligand deficiency). Case report

Hyper-IgM (HIGM) is an inborn error of immunity primarily caused by genetic defects in the CD40-CD40 ligand (CD40L) pathway. The main clinical features consist of recurrent sinopulmonary and opportunistic infections and the development of autoimmune manifestations such as neutropenia, but neurologic manifestations are rare.

On May 10th, 2023, a 9 year-old boy with XHIGM, was admitted to a third level hospital because of one-month history of distal muscle weakness and involuntary irregular movements of trunk and upper limbs. Physical and neurological examination showed involuntary, non-suppressive irregular dancing movements that corresponded to choreoathetosis. Blood tests showed: Hemoglobin 11.8 g/dl, WBC 5,700/microL, neutrophils 1,400/microL, lymphocytes 3,300/microL and PLT 336,000/mm3, CRP 1.43mg/dl and ESR 26mmHr. Brain MRI was normal. A diagnostic LP was performed and CSF analysis showed: 6 leucocytes/mm3, total protein 31mg/dl and a glucose level of 62mg/dl (2/3 of serum glucose). CSF cultures, galactomannan antigen, gram stain and RT-PCR were negative. Rheumatic fever diagnosis was ruled out because the patient didn’t fulfill Jones criteria and had a negative S. pyogenes throat culture and ASLO in 226 IU. Finally, an autoimmune etiology was ruled out with laboratory workup within normal range values (ANA negative, ANCA negative, anti-SCL70 < 2 U/mL, anti-RNP < 2 U/mL, SMA < 2 U/mL, anti-LKM1 antibody: 3.92 U/mL, antiphospholipid antibodies negative, SSA/SSB antibodies <2 U/mL, C3 181 mg/dl and C4 27.4 mg/dl). The patient was treated with intravenous gammaglobulin 2 gkgdose, methylprednisolone 0.8mgkgday and risperidone, with an excellent response and almost resolution of choreiform movements after 2 weeks of treatment. Movement disorders are unusual manifestations described in CD40L deficiency, especially at this age, and the pathophysiology is still largely unclear, which draws special attention to this patient that developed idiopathic choreoathetosis with major impact in daily activity but responded successfully with anti-inflammatory and immunomodulatory treatment.

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