Association Between MEN1 Gene and AIHA

Fatihin Abdul Razak; Nur Aini Eddy Warman; Mohd Hazriq Awang; Aimi Fadilah Mohamad; Nur Haziqah Baharum; Fatimah Zaherah Mohamed Shah; Rohana Abdul Ghani

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Association Between MEN1 Gene and AIHA

Author: Fatihin Abdul Razak ¹ ; Nur Aini Eddy Warman ¹ ; Mohd Hazriq Awang ¹ ; Aimi Fadilah Mohamad ¹ ; Nur Haziqah Baharum ¹ ; Fatimah Zaherah Mohamed Shah ¹ ; Rohana Abdul Ghani ¹
Author Information

1. Department of Internal Medicine, Faculty of Medicine, Universiti Teknologi MARA
Publication Type:Journal Article
From: Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):99-
CountryPhilippines
Language:English
Abstract: Introduction:Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome caused by mutations in the tumor suppressor gene MENIN, classically characterized by endocrine tumors of the parathyroid glands, pancreas, and pituitary. Beyond tumorigenesis, emerging evidence suggests a role for MENIN in immune regulation, with deficiency linked to CD4⁺ and CD8⁺ lymphocyte dysfunction and predisposition to autoimmunity. While autoimmune conditions such as thyroiditis and pernicious anemia have been described in MEN1, an association with autoimmune hemolytic anemia (AIHA) has not been previously reported. We describe a rare case of MEN1 associated with warm AIHA, highlighting a potential link between endocrine tumorigenesis and immune dysregulation.
Case:A 56-year-old female presented with a 4-month history of lethargy, anorexia, weight loss, and painless jaundice. She is para 6 + 1, with no history of anemia in pregnancy, prior blood transfusions, or family history of hematological disorders. Examination revealed mild pallor, jaundice, and hepatomegaly without splenomegaly. She had a prior diagnosis of MEN1, with two hallmark features: primary hyperparathyroidism and a pancreatic neuroendocrine tumor. She underwent pancreatic enucleation, hemithyroidectomy, and hemiparathyroidectomy; histopathology demonstrated a benign thyroid nodule and parathyroid hyperplasia. Whole exome sequencing identified no pathogenic MEN1 mutation but revealed a c.1621A>G variant, classified as a non-deleterious polymorphism. Variants in TP53 and BRCA1 were also detected without phenotypic expression. Surveillance colonoscopy and mammography were unremarkable. Laboratory findings were consistent with warm AIHA, including elevated lactate dehydrogenase, indirect hyperbilirubinemia, low haptoglobin, reticulocytosis, and a positive direct Coombs test (immunoglobulin G). Peripheral blood film was nonspecific. She responded well to a tapering course of prednisolone.
Conclusion:This case highlights a possible association between MEN1 and autoimmune hemolysis. The presence of the MEN1 c.1621A>G variant, alongside TP53 and BRCA1 variants, raises the possibility of modifier effects influencing immune dysregulation. Further studies are needed to clarify this relationship.
Full text:2026080416260360425EP_A143.pdf