Rare Biallelic Variants Affecting the Interdomain B Region of Zeta-Chain Associated Protein Kinase 70 (ZAP70) Protein in a Sudanese Patient: Case Report

Abstract

Alamin Mustafa,1 Rogaia Hasap Alrasoul Ahmed,2 Hala Hamza Eltayeb,2 Malaz Elsadeg,2 Omaima Abdel Majeed Mohamed Salih,3 Nahla HH Erwa4 1Al-Neelain University, Faculty of Medicine, Khartoum, Sudan; 2Faculty of Medicine, Omdurman Islamic University, Omdurman, Sudan; 3Departments of Pediatrics and Child Health, Tropical and Infectious Diseases Consultant, Clinical Immunologist, Faculty of Medicine and Health Sciences, Omdurman Islamic University, Omdurman, Sudan; 4Clinical Immunology Consultant, Faculty of Medicine, University of Khartoum, Khartoum, SudanCorrespondence: Alamin Mustafa, Email [email protected]: A class of disorders known as inborn errors of immunity (IEI) is defined by a compromised or missing immune response, which increases the vulnerability to infections, immunological dysregulation, and cancer. Severe combined immunodeficiencies (SCIDs), affecting both T and B-cell function are rare but often severe diseases. In this report, we describe a 10-month-old SCID patient from Sudan with disseminated BCG infection.Case Presentation: A 10-month-old boy whose parents were first degree relatives, presented with a six-month history of repeated chest infections and fever. Physical examination revealed a very ill-looking boy with respiratory distress dependent on oxygen, had slight abdominal distention and hepatomegaly. Investigations revealed positive polymerase chain reaction (PCR) for M. tuberculosis complex infection and low CD4+ and CD8+ cells. Genetic testing showed compound heterozygosity in trans for two variants in the Zeta-chain Associated Protein Kinase 70 (ZAP70) gene associated with autosomal recessive SCID. The patient was started on BCG-related infection treatment, intravenous immunoglobulin (IVIG) replacement and trimethoprim/sulfamethoxazole prophylaxis with an excellent response and the patient responded well to the treatment.Conclusion: SCIDs are rare, and early management is crucial. In this case, a diagnosis of ZAP70 deficiency was based on next-generation sequencing and inhouse bioinformatic computational analysis of the ZAP70 gene, highlighting the importance of genetic testing in the workup of immunodeficiencies in low resource settings.Keywords: Inborn errors of immunity, SCID, disseminated BCG infection, ZAP70 deficiency, pediatric immunology

Keywords

• inborn errors of immunity
• scid
• disseminated bcg infection
• and zap70 deficiency
• and pediatric immunology.