August 2007 Vol 7 copy.indd Omenn’s Syndrome A rare primary immunodeficiency disorder *Ibtisam B Elnour,1 Shakeel Ahmed,2 Kamal Halim,3 V Nirmala4 SULTAN QABOOS UNIVERSITY MEDICAL JOURNAL AUGUST 2007 VOL 7, NO. 2, P. 133-138 SULTAN QABOOS UNIVERSITY© SUBMITTED - 25TH APRIL 2007 OMENN’S SYNDROME IS A RARE AUTOSOMAL recessive form of severe combined immun-odeficiency. Omenn GS first described it in 1965. He described an extended American-Irish fam- ily with clinical features of recurrent infections, skin eruptions, eosinophilia, lymphadenopathy and hepat- osplenomegaly with accompanied respiratory, gastroin- testinal symptoms and failure to thrive. T lymphocyte numbers may be normal or high, but eosinophils are virtually increased. There is marked lymphocyte deple- tion in the thymus and lymphoid tissue. A given subset of T lymphocytes represents the majority of the blood T cells in each patient. Elevated numbers of T cells are found in the skin and gut, some of which have the phenotype of activated T cells. Omenn’s syndrome is fatal if untreated. Patients have life-threatening bacte- rial, viral and fungal infections as in other forms of se- vere combined immunodeficiency. Allogenic haemat- opoitic stem cell transplant has treated the condition successfully. Omenn’s syndrome is a genetically heterogeneous condition. Patients with similar immunophenotypes may have as yet unidentified gene defects. The major- ity of mutations are missense mutations in recombi- nase activating genes RAG-1 and RAG-2, which have been mapped to chromosome band 11p13. Mutation in RAG-1 and RAG- 2 results in partial V(D)J recombina- tion activity and dysregulation of T and B cell functions. Recent publications have described Omenn’s syndrome in the absence of RAG mutations. Omenn’s syndrome has been reported in patients from North America, Europe and Asia. El-Arabi re- ported an infant with Omenn’s syndrome from Qatar. To our knowledge, there is no other report from the Arabian area.1 C A S E R E P O R T اومني متالزمة االولي املناعة لنقص نادر اضطراب نرماال في حليم، شاكيل احمد، كمال النور، ابتسام مسقط قابوس ، السلطان جامعة مستشفى في الشديد نقص املناعة املركب من عديدة انواع تشخيص مت 17 املاضية ال السنوات : في امللخص أسابيع كان ــتة س عمره رضيع عماني هنا نعرض . ــديد الش ملركب املناعة لنقص املتنحية ــدية الوراثة الصبغية اجلس من نادرة اومني حالة متالزمة . . النادرة لهذه املتالزمة ملناعية اجلوانب خاللها من ناقشنا . املتالزمة لتلك واملناعية السريرية الصفات عليه باديا عمان. حالة، تقرير أولى، الشديد، املركب املناعة نقص املناعة، نقص اومني، الكلمات: متالزمة مفتاح 1Department of Child Health, College of Medcine and Health Sciences, Sultan Qaboos University, P. O. Box 35, Al-Khod 123, Muscat, Sultanate of Oman; 2College of Medicine, Agha Khan University, Karachi, Pakisthan; 3Department of Immunology, Military Hospital, Riyadh, Kingdom of Saudi Arabia; 4Department of Pathology, PSG Institute of Medical Sciences and Research, Coimbatore, Tamil Nadu, India. *To whom correspondence should be addressed. Email: ibtisamb@squ.edu.om ABSTRACT: Over the last 7 years different forms of severe combined immunodeficiency have been diagnosed at Sultan Qaboos University Hospital, Muscat. Omenn’s syndrome is a rare autosomal recessive form of severe combined immunodeficiency. We report a 6 weeks old Omani infant who presented with the characteristic clinical and immunological phenotype of Omenn’s syndrome. We take the opportunity to discuss and review the immunological aspect of this rare syndrome. Keywords: Omenn’s Syndrome; Immunodeficiency, severe, combined; Immunodeficiency, primary; Case report; Oman. I B T I S A M B E L N O U R , S H A K E E L A H M E D , K A M A L H A L I M A N D V N I R M A L A 134 C A S E R E P O R T A 6 weeks old Omani male infant was referred to Sultan Qaboos University Hospital with generalized lymphad- enopathy and gross hepatomegaly. He was the second child of consanguineous parents, delivered normally with a birth weight of 3.5 kg. He received the BCG and the first dose of oral polio vaccine (OPV), together with hepatitis B vaccines immediately after birth accord- ing to the routine schedule of immunization in Oman. The first child in the family was normal. Symptoms were first noticed at the age of 3 weeks with progres- sive diffuse erythrodermic scaly skin rashes, which spread over the whole body including the scalp. This was diagnosed and treated as extensive seborrheic der- matitis. Two weeks later, the mother noticed swelling of the face, neck and at the subaxillary areas. Physi- cal examination revealed a febrile and sick baby who had generalized lymphadenopathy with huge cervical lymph nodes, oedema of the face and the extremities, diffuse erythrodermic scaly icthyotic skin rashes over the entire body and hepatosplenomegaly of 4cm each. Cardiovascular, respiratory and neurological examina- tions were normal. A complete range of hematological, immunological and biochemical tests was performed. Blood test showed haemoglobin of 9.3g/dl, leukocyte count of 40.3x109/l, of which the neutrophil count was 7.92x109/l and lymphocyte count was 11.8X109/l. The eosinophils count was very high (17.4x 109/l). The platelet count was normal. Flow cytometry analysis of peripheral blood cells revealed lymphocytosis with vir- tually absent B cells as marked by anti CD20. All lym- phocytes were CD3+. There was oligoclonal predomi- nance of activated memory cells CD4+/CD29, [Table 1]. Bone marrow aspiration confirmed the absence of B cells and T cells were present. Human leukocyte an- tigen typing revealed that the child was not identical to his mother. Serum immunoglobulin levels were low except for extremely high serum IgE levels. In the absence of B cells, IgG level was certainly of maternal origin. IgE level was 19188.0 kiu/l and later rose to 25200 kiu/l [Table 2]. Evaluation of cytokines revealed normal interleukin 4 < 5pg/ml and high interleukine 5 level 25 pg/ml (nor- mal