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

Introduction: 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.

Case report: Insulin desensitization as the only option for managing insulin allergy in a Sudanese patient.

Introduction: Allergic reactions to insulin have become very rare with the introduction of human insulin. Anaphylaxis is a life-threatening condition that results from immediate IgE-mediated hypersensitivity. Desensitization to human insulin was reported to control immediate hypersensitivity reactions to insulin. Here, we describe the history and challenges of managing our patient and the development of an insulin desensitization protocol in a resource-limited setup. Case Summary: A 42-year-old Sudanese woman with poorly controlled type 2 diabetes on maximum antidiabetic medications required insulin therapy to achieve reasonable glycemic control. She developed progressive and severe immediate hypersensitivity reactions to insulin, including anaphylaxis. Serum sample analysis demonstrated insulin-specific IgE antibodies. The patient's poor glycemic control and the need for breast surgery indicated insulin desensitization. A 4-day desensitization protocol was delivered in an ICU bed for close observation. Following successful desensitization and 24-h observation, our patient was discharged on pre-meal human insulin, which was tolerated well to the current date. Conclusions: Although insulin allergy is rare, once encountered, it is very challenging in patients who have no other treatment options available. Different protocols for insulin desensitization are described in the literature; the agreed protocol was implemented successfully in our patient despite the limited resources.

Allergic manifestations of inborn errors of immunity and their impact on the diagnosis: A worldwide study.

Background: Allergies have long been observed in Inborn Errors of Immunity (IEI) and might even be the first presentation resulting in delayed diagnosis or misdiagnosis in some cases. However, data on the prevalence of allergic diseases among IEI patients are limited and contradictory. Objective: To provide a worldwide view of allergic diseases, across a broad spectrum of IEI, and their impact on the timely diagnosis of IEI. Methods: This is a worldwide study, conceived by the World Allergy Organization (WAO) Inborn Errors of Immunity Committee. A questionnaire was developed and pilot-tested and was sent via email to collect data from 61 immunology centers known to treat pediatric and/or adult IEI patients in 41 countries. In addition, a query was submitted to The United States Immunodeficiency Network (USIDNET) at its website. Results: Thirty centers in 23 countries caring for a total 8450 IEI patients responded. The USIDNET dataset included 2332 patients. Data from responders showed that a median (IQR) of 16.3% (10-28.8%) of patients experienced allergic diseases during the course of their IEI as follows: 3.6% (1.3-11.3%) had bronchial asthma, 3.6% (1.9-9.1%) atopic dermatitis, 3.0% (1.0-7.8%) allergic rhinitis, and 1.3% (0.5-3.3%) food allergy. As per the USIDNET data, the frequency of allergy among IEI patients was 68.8% (bronchial asthma in 46.9%). The percentage of IEI patients who presented initially with allergic disorders was 8% (5-25%) and diagnosis delay was reported in 7.5% (0.9-20.6%). Predominantly antibody deficiencies had the highest frequency of allergic disease followed by combined immunodeficiency with a frequency of 40.3% (19.2-62.5%) and 20.0% (10-32%) respectively. As per the data of centers, anaphylaxis occurred in 25/8450 patients (0.3%) whereas per USIDNET dataset, it occurred in 249/2332 (10.6%); drugs and food allergy were the main causes in both datasets. Conclusions: This multinational study brings to focus the relation between allergic diseases and IEI. Major allergies do occur in IEI patients but were less frequent than the general population. Initial presentation with allergy could adversely affect the timely diagnosis of IEI. There is a need for policies to raise awareness and educate primary care and other referring specialties on the association of allergic diseases with IEI. This study provides a network among centers for future prospective studies in the field.