A young girl with hypogammaglobulinemia and granulomatous hepatitis caused by a novel mutation in ZBTB24 gene: A case based analysis

Abstract

Background: Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome(s) are a group (ICF1 to ICF4) of autosomal recessive combined immunodeficiency disorders that may mimic common variable immunodeficiency (CVID) at initial presentation. Unlike CVID, autoimmune manifestations have been reported uncommonly in patients with ICF2.

Procedure: Herein we describe a new case of ICF2 with a novel ZBTB24 mutation and granulomatous hepatitis, with a literature review of all patients with ZBTB24 mutations.

Results: Post-neonatal hepatitis, reported in only 2 patients of ICF2 till date, was the presenting manifestation of the index child with ICF2. Evaluation revealed a homozygous mutation in ZBTB24 gene (c.433_434delGC, p.Ala145ProfsTer7). On literature review a total of 39 cases with ZBTB24 mutations reported till date were found, with two-thirds of reported patients being males. Respiratory tract infections and facial anomalies are commonest clinical features seen in more than 80 % of the patients. All patients who have immunoglobulin levels tested have at least 1 isotype decreased with decreased B cell number seen in at least one-third of patients. Decreased IgG and IgA levels are seen more frequently in patients with truncation mutations as compared to missense mutations. Candidiasis and Pneumocystis infections have been reported only in patients with truncation mutations.

Conclusions: Facial features should be looked for in all patients presenting with hypogammaglobulinemia. Next generation sequencing should be considered in patients who have a CVID like presentation in early age with unusual manifestations.

Keywords: CVID; Granuloma; Hepatitis; Hypogammaglobulinemia; ICF2; ZBTB24.