Hyperimmunoglobulin syndrome due to CD40 deficiency: possibly the first case from India

• Published in: Journal of postgraduate medicine Vol. 61; no. 1; pp. 46 - 48
• Main Authors: Mishra, A, Italia, K, Gupta, M, Desai, M, Madkaikar, M
• Format: Journal Article
• Language: English
• Published: India Medknow Publications and Media Pvt. Ltd 01-01-2015; Medknow Publications & Media Pvt. Ltd; Medknow Publications & Media Pvt Ltd
• Subjects: Analysis; Antibiotics; B-Lymphocytes - metabolism; Bacterial infections; Blood; Case Report; Case studies; Causes of; CD40 Ligand - genetics; Child, Preschool; Deoxyribonucleic acid; Diarrhea; DNA; Endoplasmic reticulum; Female; Humans; Hyper-IgM Immunodeficiency Syndrome - blood; Hyper-IgM Immunodeficiency Syndrome - genetics; Hypergammaglobulinemia - diagnosis; Hypergammaglobulinemia - genetics; Hypergammaglobulinemia - immunology; Immune system; Immunoglobulin M; Immunoglobulin M - blood; Immunologic Deficiency Syndromes - diagnosis; Immunologic Deficiency Syndromes - genetics; Immunologic Deficiency Syndromes - immunology; Immunologic diseases; India; Infections; Lymphocytes; Mutation; Patients; Physiological aspects; Rare Diseases; T cells; India
• ISSN: 0022-3859; 0972-2823
• DOI: 10.4103/0022-3859.147053

Hyperimmunoglobulin M (HIGM) type 3 due to CD40 deficiency is a very rare syndrome. Only 16 cases have been reported thus far. The clinical presentation is very variable. We present the first case of this rare disorder from India. The case is of a two-and-a-half-year-old female, with a history of repeated episodes of skin infections and diarrhea since birth. Laboratory evaluation revealed elevated absolute lymphocyte count and an absolute neutrophil count (ANC) of 1026/mm3. The lymphocyte subset analysis showed normal absolute counts of Natural Killer (NK) cells and elevated absolute counts of T-cells (CD4 and CD8) and B-cells. The serum immunoglobulin estimation showed low levels of IgG, IgA, IgE and an elevated level of IgM. The CD154 analysis was normal and expression of CD40 was absent on the B-cells. Molecular analysis showed a novel mutation, with deletion of 3bp (AAG) [p.Glu107GlyfsX84] in the homozygous state, in the CD40 gene. Thus the patient was diagnosed as HIGM type 3. The parents were screened and counseled regarding prenatal diagnosis at the time of next pregnancy.