Salem Al-Tamemi

Primary immunodeficiency diseases in oman: five years' experience at sultan qaboos university hospital.

BackgroundPrimary immunodeficiency diseases (PIDs) are considered rare but are generally assumed to be more common in Middle Eastern countries. The prevalence and characteristics of PIDs are unknown in Oman.MethodsSultan Qaboos University Hospital is the national referral center for PID in Oman during the study period. Patients were diagnosed and classified according to the clinical and laboratory criteria of PID reported by the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee. A registry was created, and patient data were analyzed between July 2005 and July 2010.ResultsOver a 5-year period, there were a total of 90 patients, with an estimated prevalence of 4.5 cases per 100,000. The most common form of immunodeficiency was phagocyte disorders (42%), mainly chronic granulomatous disease, followed by predominantly antibody disorders (18%), other well-defined PID syndromes (13%), and combined immunodeficiencies (12%). The median age of onset of symptoms was 9 months. The median age of diagnosis was 24 months. Consanguinity was present in 81% of patients. The most common infectious presentation was pneumonia (42%), followed by deep abscess (27%) and BCGosis (12%). A total of 25% of patients required intravenous immunoglobulins treatment, 4% required gamma interferon therapy, and 11% underwent bone marrow transplantation. Of all PID patients, 90% survived treatment, whereas 10% did not.ConclusionsThe estimated minimum prevalence of PID in Oman is 4.5 cases per 100,000, with a predominance of phagocyte disorders. Consanguinity is a significant factor; pneumonia and deep abscesses were the main infectious presentations. The overall survival rate was 90%. Strategies are needed to improve the care for PID patients and to increase the awareness among parents and physicians.

Complete DiGeorge Anomaly in the Absence of Neonatal Hypocalcemia and Velofacial and Cardiac Defects

We report an atypical case of complete DiGeorge (DG) anomaly that presented initially exclusively as severe combined immunodeficiency (SCID). The child had severe infections at diagnosis, in keeping with the SCID phenotype; however, normal lymphocyte counts and immunoglobulin levels were noted at admission, which delayed diagnosis. Importantly, the child presented without neonatal hypocalcemia or velofacial or cardiac abnormalities at the time of diagnosis, which masked underlying DG. This case outlines the difficulties in making the diagnosis of SCID in a timely manner and illustrates the variation in presentation of the 22q11.2 deletion syndrome. There should be a high index of suspicion for primary immunodeficiency among children with severe infections and, because management may vary, DG anomaly should be considered in the differential diagnosis of T− B+ natural killer+ SCID.

Chediak-Higashi syndrome: novel mutation of the CHS1/LYST gene in 3 Omani patients.

Background: Chediak-Higashi syndrome (CHS) is a rare, autosomal, recessive lysosomal disorder with hematological and immunologic abnormalities; however, stem-cell transplantation from a matched or related donor may be curative. Many mutations of the CHS1/LYST gene have been reported to date. We report a novel nonsense mutation of the CHS1/LYST gene in 3 Omani patients. Methods and Results: Three patients from 2 different families presented with clinical and laboratory features of CHS and a history of death of a previous sibling because of a severe illness, suggestive of the accelerated phase of CHS. Giant granules were present in the myeloid cell lines. Before the stem-cell transplant, the first patient underwent gene sequencing of all exons of the lysosome trafficking regulator (CHS1/LYST) gene and revealed a nonsense mutation in exon 5 (c.925C>T, p.R309X). Subsequently, upon presentation, the second and third patients’ direct gene sequencing of exon 5 revealed the same mutation. Conclusions: We report a nonsense mutation in exon 5 (c.925C>T, p.R309X). This supports the allelic heterogeneity of CHS and is in line with most reported mutation types that lead to a truncated protein. Identification of the mutation type will facilitate timely diagnosis, management, and family counseling for those with affected children in Oman.

Combined immunodeficiency due to a homozygous mutation in ORAI1 that deletes the C-terminus that interacts with STIM 1.

ORAI1 is the pore-forming subunit of the calcium release-activated calcium channel responsible for calcium influx into cells triggered by endoplasmic reticulum store depletion. We report here a patient with severe combined immunodeficiency and absent store-operated calcium entry due to a novel mutation in ORAI1 that results in the expression of a C-terminally truncated protein that abolishes ORAI1 binding to STIM1.

Semaphorin 4C: A Novel Component of B-Cell Polarization in Th2-Driven Immune Responses

[This corrects the article on p. 558 in vol. 7, PMID: 28003812.].