Mendelian Susceptibility to Mycobacterial Disease

Mendelian susceptibility to mycobacterial diseases (MSMD) represents a group of inherited immune system disorders characterized by interferon-gamma (IFN-γ) deficiency, making individuals susceptible to infections caused by environmental mycobacteria and other intracellular pathogens. 

An 8-year-old boy exhibited recurrent fever and multiple neck swellings, leading to ulceration after the lymph node swellings increased and ruptured. 

The child was the second of five siblings born to third-degree consanguineous parents. His neck swellings had persisted for two years. 

Despite no history of Koch's contact or BCGosis, the patient underwent Category 1 antitubercular treatment (Cat 1 AKT) for four months due to suspected tuberculosis (TB).

Non-resolving skin lesions and the development of a chest wall abscess while on AKT raised concerns about multidrug-resistant tuberculosis (MDR TB). Tests for mycobacterial and non-tubercular mycobacteria (NTM) using GeneXpert and Mycobacterial Growth Indicator Tube (MGIT) yielded no growth.A skin biopsy from the neck wound's edge revealed features suggestive of scrofuloderma caused by M. ulcerans. HIV testing and assessments of serum immunoglobulin levels, lymphocyte subsets, and nitroblue tetrazolium showed normal results. Investigation for MSMD disclosed the absence of CD212 (IL12β) expression on activated T cells, and subsequent genome sequencing identified an IL12RB1 defect [c.493C>T (p.Gln165Ter)] mutation. 

The patient received MDR AKT for 18 months and Clarithromycin for NTM, with flap reconstruction performed for the neck ulcers. 

However, two months later, similar lesions recurred. Due to the unavailability of interferon-gamma (IFNG) in India, hematopoietic stem cell transplantation (HSCT) was planned after resolving the infection, representing the sole known curative treatment. 

The child's manifestation of environmental mycobacteria prompted consideration of primary immunodeficiency, emphasizing the importance of identifying signature organisms to assess the immunological axis.

Source: Sanap R, David J, Chattopadhyay N, Vaswani RK.Indian Journal of Pediatrics. 2024 Feb.