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Background <p>Very early onset inflammatory bowel disease (VEOIBD), defined as onset before six years of age, is increasingly recognized as a distinct entity often linked to monogenic etiologies. Data from the Middle East remain limited.</p> Methods <p>We conducted a retrospective case series of ten pediatric patients diagnosed with VEOIBD at King Abdullah University Hospital, Jordan, between July 2017 and July 2024. Clinical, endoscopic, histopathologic, genetic, treatment, and outcome data were extracted and analyzed descriptively.</p> Results <p>The cohort comprised ten patients (six males, four females). Median age at symptom onset was 12 months (range 3–60), with median diagnosis at 34 months (range 10–72). Diarrhea (100%), failure to thrive (60%), and recurrent infections (40%) were predominant presenting features. Endoscopy revealed mucosal ulceration in seven patients (70%), with non-caseating granulomas in three (30%) and focal active colitis in three (30%). Genetic testing (<i>n</i> = 8) identified pathogenic or likely pathogenic variants in six patients and variants of uncertain significance (VUS) in two; the genes implicated were MEFV (<i>n</i> = 3), CYBB (<i>n</i> = 2; both VUS), G6PC3, GUCY2C, NPC1, NOD2, RIPK1, and LRBA. Three patients carried variants in two genes. In one pair — a homozygous pathogenic NPC1 frameshift variant with a heterozygous NOD2 VUS — a composite digenic mechanism has been proposed as a candidate contributor to the unusually severe VEOIBD phenotype [21]. Therapies included infliximab (<i>n</i> = 4), mesalazine, azathioprine, budesonide, intravenous immunoglobulin, elemental diet, and colchicine. Three patients were referred for hematopoietic stem cell transplantation (HSCT); one died of infection-related multi-organ failure. The patient with a homozygous LRBA VUS lacked access to targeted therapy with abatacept or sirolimus.</p> Conclusions <p>VEOIBD in Jordan is characterized by early presentation, genetic heterogeneity including co-occurring variants of uncertain significance, and poor response to conventional therapy. Limited access to targeted agents and HSCT significantly impacts outcomes. Early genomic testing, multidisciplinary management, and improved therapeutic access are essential for better prognosis.</p>

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Very early onset inflammatory bowel disease in Jordan: a single-center case series of clinical, genetic, and therapeutic features

  • 期刊论文

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  • 发表日期：

    2026年7月25日

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  • Eyad Altamimi,
  • Hala Almomani,
  • Ayah Alsmadi,
  • Nicole Issi,
  • Maria Shurman

摘要

Background

Very early onset inflammatory bowel disease (VEOIBD), defined as onset before six years of age, is increasingly recognized as a distinct entity often linked to monogenic etiologies. Data from the Middle East remain limited.

Methods

We conducted a retrospective case series of ten pediatric patients diagnosed with VEOIBD at King Abdullah University Hospital, Jordan, between July 2017 and July 2024. Clinical, endoscopic, histopathologic, genetic, treatment, and outcome data were extracted and analyzed descriptively.

Results

The cohort comprised ten patients (six males, four females). Median age at symptom onset was 12 months (range 3–60), with median diagnosis at 34 months (range 10–72). Diarrhea (100%), failure to thrive (60%), and recurrent infections (40%) were predominant presenting features. Endoscopy revealed mucosal ulceration in seven patients (70%), with non-caseating granulomas in three (30%) and focal active colitis in three (30%). Genetic testing (n = 8) identified pathogenic or likely pathogenic variants in six patients and variants of uncertain significance (VUS) in two; the genes implicated were MEFV (n = 3), CYBB (n = 2; both VUS), G6PC3, GUCY2C, NPC1, NOD2, RIPK1, and LRBA. Three patients carried variants in two genes. In one pair — a homozygous pathogenic NPC1 frameshift variant with a heterozygous NOD2 VUS — a composite digenic mechanism has been proposed as a candidate contributor to the unusually severe VEOIBD phenotype [21]. Therapies included infliximab (n = 4), mesalazine, azathioprine, budesonide, intravenous immunoglobulin, elemental diet, and colchicine. Three patients were referred for hematopoietic stem cell transplantation (HSCT); one died of infection-related multi-organ failure. The patient with a homozygous LRBA VUS lacked access to targeted therapy with abatacept or sirolimus.

Conclusions

VEOIBD in Jordan is characterized by early presentation, genetic heterogeneity including co-occurring variants of uncertain significance, and poor response to conventional therapy. Limited access to targeted agents and HSCT significantly impacts outcomes. Early genomic testing, multidisciplinary management, and improved therapeutic access are essential for better prognosis.