JAGN1-Associated Congenital Neutropenia with G-CSF Intolerance and Multisystem Morbidity: A Case Report and Consideration for Curative Stem Cell Transplantation

JAGN1-associated neutropenia is a rare autosomal recessive form of severe congenital neutropenia (SCN), with fewer than 35 patients reported worldwide. The JAGN1 gene encodes an endoplasmic reticulum-resident protein essential for neutrophil differentiation and G-CSF signaling. Most patients are poor responders to G-CSF, and allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the only curative option. Limited literature exists on long-term multisystem complications in adult patients with JAGN1 deficiency.

A 42-year-old female with chronic congenital neutropenia diagnosed decades earlier presented for hematologic evaluation. She had been on long-standing intermittent filgrastim with minimal response and significant intolerance, including severe bone pain limiting use to episodes of active infection only. Her clinical course was marked by recurrent severe infections requiring extensive surgical intervention: multiple tympanoplasties for chronic otitis media resulting in bilateral hearing loss, recurrent cutaneous abscesses requiring incision and drainage, and surgical debridement of mastitis with wound vacuum placement. Additional diagnoses included hidradenitis suppurativa, iron deficiency anemia, and bilateral carpal tunnel syndrome. Two prior bone marrow biopsies were morphologically unremarkable. A comprehensive hereditary neutropenia mutation panel confirmed a pathogenic JAGN1 mutation. Laboratory workup including copper (128 µg/dL), folate (9.3 ng/mL), and vitamin B12 (391 pg/mL) was normal, excluding nutritional causes. The patient was clinically stable (ECOG 1, Karnofsky 90%), afebrile, and without active infection. Given refractory neutropenia and the known risk of MDS/AML transformation in SCN, she was referred for curative-intent alloHSCT evaluation. She was also referred to hepatology for fatty liver disease workup.

This case highlights the substantial cumulative morbidity of JAGN1-related SCN, including irreversible hearing loss and recurrent soft tissue infections requiring repeated surgical intervention. Notably, G-CSF intolerance - rather than classic nonresponse alone - drove the transplant referral, an underrecognized indication. The coexistence of hidradenitis suppurativa may represent an underappreciated phenotypic manifestation of JAGN1 deficiency and neutrophil dysfunction. In the largest multicenter study, all 32 JAGN1-deficient patients experienced infectious complications, and six underwent alloHSCT for refractory neutropenia. This case also illustrates the multidisciplinary coordination required across hematology, transplant medicine, and gastroenterology.

JAGN1 mutations can produce severe, G-CSF-refractory congenital neutropenia with substantial multisystem morbidity. This case adds to the limited literature on adult outcomes in JAGN1 deficiency and supports early consideration of curative alloHSCT in G-CSF-intolerant patients.