A 4-years-old child, born in March 2021, the second son of a non-consanguineous marriage, from Tenango del Valle, Mexico. He was premature (32 weeks). Neonatal screening test of congenital hypothyroidism, galactosemia, adrenal hyperplasia, phenylketonuria, and biotinidase deficiency, was normal and his sibling is healthy. Neurodevelopment was normal. History of non-specified severe infections in her family and any other relevant medical information.
He received BCG vaccine at birth, and 3 months later a local edema appeared, which self-resolved one month later without treatment. Seven months later, showed 2 retro auricular masses that got resolved without treatment. In June 2019 (at 2 years), a regional left armpit lymphadenitis due to BCGitis was diagnosed, and received rifampicin for unknown time without improvement.
On April 2020, the patient was remitted for the first time to our hospital and a ganglionic tuberculosis was diagnosed by a lymph node biopsy. Blood cell count analysis showed leukocytosis, neutrophilia, and lymphocytosis and was treated for nine months with isoniazid (6 mg/kg/day), rifampicin (12mg/kg/day), pyrazinamide (32mg/kg/day), and ethambutol (24mg/kg/day). On January 3rd 2021, at the age of 3 years, presented non-productive cough, rhinorrhea and odynophagia, treated with symptomatic drugs. Ten days later, arrived to our hospital presenting tachypnea, tachycardia, fever, and oxygen desaturation (84%) and then SARS-CoV-2 infection was detected by a quantitative polymerase chain reaction on January 19th. The patient had a favorable evolution and did not require invasive mechanical ventilation nor aminergic support.
After recovering from SARS-CoV-2 infection, the patient had persistent fever and paroxysmal hemoptysis requiring blood transfusion on January 21st; and ceftriaxone IV 75mg/kg/12hrs was initiated. Simple and contrasted computed tomography (CT) scans found bilateral pleural effusions and brain abscesses, so thoracentesis, gastric liquid sampling and drainage of brain abscesses were done on January 22nd. Bacilloscopy and GenExpert analysis were positive to Mycobacterium tuberculosis resistant to rifampicin and isoniazid in the brain abscess and pleural effusions. Serology for HIV, HBV, HCV and adenosine deaminase in pleural liquid, were normal. Levofloxacin (20mg/kg/day), amoxicillin with clavulanic acid (75mg/kg/day), linezolid (20mg/kg/day), propionamid (18mg/kg/day), cicloserin (18mg/kg/day) and fluconazole (6mg/kg/day) were given.
Additional 15ml of drainage of a brain abscess was done on February 5th 2021. Another head CT done on February 11th found a new brain abscess nearby the ventricular wall (15.7 x 22.25mm). On February 15th, Chronic granulomatous disease was ruled out after negative results of the reduction of nitroblue tetrazolium and dihydroergotamine techniques. A flow cytometry showed a low count of CD4 and CD3 lymphocytes.
On March 13th, the patient developed intracranial hypertension by hydrocephalus; and a third ventricle ventriculostomy was performed the next day without improvement, therefore a ventriculoperitoneal shunt was performed the same day. On March 24th another microsurgical resection of brain abscesses was done without any incident.
On April 29th the expression of IL-12R and Interferon gamma receptor 1 (IFN-gammaR1) was assessed in the patient and in his family members using flow cytometry. Expression of IFN-gammaR1 and IL-12Rbeta2 were normal. However, no expression of IL-12Rbeta1 was found in the patient's CD3+ T lymphocytes, and was minor in his family compared to control.
Functionality of the IL-12R was assessed measuring IFN-gamma production in response to recombinant human interleukin 12 (rhIL12) and phytohemagglutinin (PHA) (Fig. 1 ). The patient and his parents showed decreased production of IFN-gamma in response to any of the given stimuli compared to control, especially with the combination of rhIL12 and PHA. Interestingly, his sibling showed increased basal production of IFN-gamma and higher response to PHA and rhIL12 given alone compared to control.
Functionality of the IFN-gammaR was assessed measuring tumoral necrosis factor alpha (TNF-alpha) production in response to lipopolysaccharide and IFN-gamma at different concentrations (Fig. 2 ). All the subjects showed adequate response to any of the given stimuli.
In summary, an IL-12Rbeta1 receptor complete deficiency was diagnosed in our patient.
Subsequently, right tempo-parieto-occpital tuberculomas were found and resected on May 11th and June 12th 2021. On July 1st, the patient was re-admitted to our hospital and a magnetic resonance imaging (MRI) of the head showed multiple brain abscesses (Fig. 3 ). On July 7th, the patient went through a non-successful resection of a fourth ventricle tuberculoma (Fig. 3).