Humoral immunodeficiency in congenital insensitivity to pain with anhidrosis

Abstract

Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive disorder caused by mutations in the neurotrophic tyrosine receptor kinase 1 (NTRK1) gene, which encodes the receptor for nerve growth factor. We report the clinical course of a 7-year-old girl with CIPA and proven NTRK1 mutation. In addition to recurrent dislocation of the left hip joint and avascular necrosis of the left talus, the patient also presented with recurrent infections secondary to hypogammaglobulinemia, a feature not previously known to be associated with CIPA. The patient was treated with regular administration of intravenous immunoglobulins. Conservative treatment of the recurrent left hip dislocation by cast immobilization and bracing was implemented to stabilize the joint. The implication of the immune system of the reported patient broadens the clinical phenotype associated with NTRK1 mutations.

Congenital insensitivity to pain and anhydrosis due to a rare mutation and that is complicated by inflammatory bowel disease and amyloidosis: a case report

“…However, inflammatory bowel disease is thought to be the result of a dysregulated immune system in the context of a genetically susceptible individual 12. Our patient may have developed inflammatory bowel disease due to immune dysregulation because patients with CIPA show several immune abnormalities such as defects in neutrophil chemotaxis 13, hypogammaglobulinemia 14, impaired release of neuropeptides that trigger proinflammatory mediators 15, defects in lymphocyte signaling 16, and severe Staphylococcus aureus infections 17.…”

“…(ii) Chronic osteomyelitis, where amyloidosis due to osteomyelitis is a late and infrequent complication 20, 23; in a large series on secondary amyloidosis, osteomyelitis was the etiologic condition in 2% of cases 20. (iii) CIPA and NTRK1 signaling pathway, where patients with CIPA show several immune and inflammatory abnormalities 14, 15. Additionally, renal amyloidosis was reported in one patient with CIPA 4.…”

Congenital Insensitivity to Pain and Anhydrosis: A Report of Two Cases

“…15 There is no convincing evidence correlating the levels of immunoglobulin with manifestations in CIPA, and it is not clear whether these could be the cause for recurrent infections. 16 Orthopaedic manifestations in CIPA 14,17,18 are musculoskeletal infections, fractures, growth disturbances, avascular necrosis, Charcot arthropathy, 19 joint dislocations, heterotopic ossification, and un-united fractures. 1 Chronic or acute-on-chronic osteomyelitis and septic arthritis of haematogenous origin are the usual presentations.…”

Novel nonsense and frameshift NTRK1 gene mutations in Chinese patients with congenital insensitivity to pain with anhidrosis

“…Abnormality in neutrophil functions and B lymphoblastoid cell lines could explain dysregulation of immune mechanisms and severe infections, which possibly bring about a chronic inflammatory response (Sato et al, 2004;Beigelman et al, 2009). A patient with CIPA has also presented recurrent infections secondary to hypogammaglobulinemia (Kilic et al, 2009). This disease was first described by Swanson in 1963.…”