A Syrian Refugee in Iraq Diagnosed as a Case of IL12RB1 Deficiency in Japan Using Dried Blood Spots.

Lika'A Fasih Y Al-Kzayer,Miyuki Tanaka,Kenji Sano,Ruwaid Behnam Y Al-Simaani,Khalid Hama Salih,Yozo Nakazawa,Ahmed K Yassin,Yusuke Okuno,Tomonari Shigemura

doi:10.3389/fimmu.2019.00058

Lika'A Fasih Y Al-Kzayer, Miyuki Tanaka + Show 7 more

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https://doi.org/10.3389/fimmu.2019.00058

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Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare condition of primary immunodeficiency disorder. Interleukin-12 receptor β1 (IL12RB1) deficiency, is the most common genetic etiology of MSMD, which is characterized by the selective predisposition to clinical disease caused by weakly-virulent mycobacteria, such as Bacillus Calmette-Guérin (BCG) vaccines, and environmental non-tuberculous mycobacteria (NTM). To the best of our knowledge, this is the first case of IL12RB1 deficiency to be reported from Iraq. Our case is an 8-year-old Syrian girl, for first-cousin parents, with a refugee-status in the North of Iraq. She had a history of disseminated BCG infection 2 months after receiving BCG vaccine, in addition to repeated episodes of mild or severe illnesses, such as maculopapular skin rash, lymphadenopathy, gastroenteritis, meningitis, and clinically diagnosed tuberculosis (TB) based on local TB-prevalence setting. Because of limited medical facilities in the war-torn countries; in Syria and Iraq, no diagnosis could be reached. We used Flinders Technology Associates (FTA) cards to transfer her bone marrow aspirate to Japan. A homozygous IL12RB1 mutation was detected by whole exome sequencing in Japan, using genomic-DNA extracted from dried bone marrow sample spots on FTA filter paper. In conclusion, diagnosis of MSMD due to IL12RB1 deficiency was possible by transferring the FTA sample of the patient for genetic evaluation in Japan. Our report recalls the need of pediatricians in countries with TB-prevalence and high parental consanguinity, to consider IL12RB1 deficiency in the differential diagnosis of a child with clinical evidence of TB, especially with the history of disseminated BCG disease.

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Primary immunodeficiency (PID) disorders are diseases that result from developmental or functional defects in the immune system
We described a case of Mendelian susceptibility to mycobacterial diseases (MSMD) due to the complete IL12RB1 deficiency in a girl of a Syrian family, who survived the difficult war situation in Syria, and fled to a camp at northern Iraq
Since it was difficult to perform adequate medical evaluation under such complicated living situations in war-torn countries, her condition was regarded as an immune deficiency of unknown cause, until the etiology could be made clear in Japan

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Primary immunodeficiency (PID) disorders are diseases that result from developmental or functional defects in the immune system. Our patient was born uneventfully in August 2010 and received BCG vaccine, according to the schedule at 7th day of age Two months later, she developed ipsilateral axillary lymphadenitis followed by generalized lymphadenopathy. At 4-year-old, as the family fled the war in Syria to a camp in northern Iraq, the child’s condition was severely deteriorated and she became seriously ill with fever, night sweating, diarrhea, and poor appetite She was referred to the intensive care unit at Hiwa Hospital in Sulaymaniyah, the northern province in Iraq. The patient did not respond to an initial course of broad-spectrum antibiotics She was treated empirically with 4 anti-TB medications for 12 months, including; isoniazid, rifampin, pyrazinamide, and streptomycin that was later changed to ethambutol. After stopping antiTB therapy, she relapsed with generalized lymphadenopathy and maculopapular skin rash (Figure 1)

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