December 2008 no white pages.indd SULTAN QABOOS UNIVERSITY MEDICAL JOURNAL NOVEMBER 2008, VOLUME 8, ISSUE 3, P. 344-346 SULTAN QABOOS UNIVERSITY© SUBMITTED - 8TH APRIL 2008 ACCEPTED - 9TH JULY 2008 Laboratory Department, Al-Nahdha Hospital, Muscat, Sultanate of Oman *To whom correspondence should be addressed. Email: sure5155@omantel.net.om Compound heterozygosity for Hb S and Hb S-Oman Case report *Suresh Venugopal, Alphonsa Shaju, Suchata Dhuri, Thuraiya Al-Harthy, Khalid B Jabal ABSTRACT The haematological and clinical findings of a three year old Omani girl, phenotypically compound heterozygote for Hb S and Hb S Oman, are presented, further substantiated by family studies. The necessity of reviewing cases with sickle cell haemoglobin in Oman is stressed. Keywords: Haemoglobin S Oman; Haemoglobin S Disease; Abnormal haemoglobin; Haemoglobinopathies; Sickle cell anaemia; Sickle cell trait; Case report; Oman. لِيّ املِنْجَ للهيموغلوبني بٌ وت املُرَكَّ الزَّيْجُ ايُرُ تَغَ � العماني لِيّ املِنْجَ والهيموغلوبني حالة تقرير جبل بيت سليم خالد احلارثي، ، ثريا شاجو، سوجاتا ذوري فينوجوبال، ألفونسا سوؤيش للهيموغلوبني وت الزَّيْجُ ايُرُ لتَغَ املركب رِيّ اهِ الظَّ طِ النَّمَ سنوات ثالث عمرها عمانية لطفلة السريرية والفحوص الدم فحوص نتائج امللخص: أظهرت حاالت وضرورة مراجعة ــة أهمي على هنا نؤكد العائلي. التاريخ ــة بدراس بعد فيما النتائج هذه ودعمت ، ــي العمان لِيّ ِنْجَ امل ــني والهيموغلوب ــيّ لِ ِنْجَ امل عمان. املنجلي في الدم بفقر اإلصابة رَيَّةِ الكُ لَّةُ خَ ، املنجلي الدم فقر ، الدم أمراض ، الطبيعي غير ، الهيموغلوبني املنجلي العماني ، الهيموغلوبني لِيّ ِنْجَ امل الكلمات: الهيموغلوبني مفتاح عمان. لِيَّة ، ِنْجَ امل THE CLASSICAL SICKLE CELL TRAIT HAS ONE βs mutation (β6 Glu‡ Val). Hb S-Oman has two mutations in cis. in the same β chain, one the classical βs mutation (β6 Glu ‡ Val), and the second (β121 Glu ‡ Lys), identical to that found in a variant namely Hb O Arab. Hb S- Oman increases the sickling tendencies, but the clini- cal symptomatology is influenced by co-existing alpha thalassaemia. No homozygous Hb S-Oman has been reported in the literature. C A S E R E P O R T A three year old Omani girl from the Al-Kindi tribe from Barka, a town on the coast about 80 km north- west of Muscat, presented to the Ear, Nose and Throat department of Al-Nahdha hospital in September 2007 with complaints of recurrent sore throat, 5-6 times a year. The clinical diagnosis was recurrent acute follic- ular tonsillitis. The past history revealed that she was diagnosed to have sickle cell anaemia with a history of haemolytic crises and frequent admissions to a terti- ary care hospital and had had a recent blood trans- fusion. A tonsillectomy was planned and a complete blood cell count (CBC) and sickling test were request- ed as preoperative investigations. The CBC showed, among other parameters: Hb - 9.34g/dl; red blood cell count - 3.45 x 1012/L; haematocrit - 22.4%; mean cell volume - 65fl; mean cell haemoglobin - 27.1pg; C A S E R E P O R T 345 C O M P O U N D H E T E R O Z Y G O S I T Y F O R H B S A N D H B S - O M A N mean cell haemoglobin concentration - 41.7g/dl and red cell distribution width - 18.9%. The sickling test was positive. From the blood film examination, the most important feature was the presence of many Napoleon hat x-shaped red blood cells and classical sickle cells [Figure 1]. The white blood cell count was 5.53 x 109/L (normal 6 -18) and platelet count was 552 x 109/L (normal 150 - 450). Given the presence of numerous Napoleon hat x-shaped red blood cells in the blood film with moderate anaemia and a posi- tive sickling test, the presence of Hb S-Oman was suspected and the patient was referred to the genetic blood screening unit of our hospital. The results of this screening were as follows: G6PD activity was normal; the high performance liquid chromatography (HPLC) profile showed: Hb A - 49%; Hb A2 - 2.3%; Hb F - 30.8%; Hb S - 12.3% and a presumptively Hb S-Oman - 5.6% in the HbC window. The presence of Hb A was believed to be due to the recent blood transfusion. The family studies revealed the HPLC profile of the father (also from the Al-Kindi tribe) to be: Hb A - 70%; Hb A2 - 3%; Hb F- 1%; Hb S- 26% and he was diagnosed as having sickle cell trait. He was clinically asympto- matic. The HPLC profile of the mother showed: Hb A - 83%; Hb A2 - 3%; Hb F - 1%, and an abnormal com- ponent in the HbC window, very likely Hb S-Oman - 13%, so she was diagnosed to have having the Hb S- Oman trait. The two brothers of the index case had normal HPLC profiles. D I S C U S S I O N This case report stresses the importance of examining the blood film, which revealed the presence of Napo- leon hat x-shaped red blood cells [Figure1] character- istic of red blood cells containing HbS-Oman.1, 2, 3 The presence, in addition, of classical sickle cells in the smear, as seen in Figure 1, prompted family stud- ies, and confirmed the inheritance of Hb S and Hb S- Oman in this patient. Thus she was diagnosed as com- pound heterozygote for Hb S and Hb S-Oman During a follow up at Al-Nahdha Hospital, after the blood transfusion, the HPLC profile of the patient revealed the presence of Hb S-Oman at 12% and Hb S at 25% matching with the level observed in her parents for respective abnormal haemoglobins. The first report of Hb S-Oman in the literature was by Langdown JV et al. in 1989.4 The first description of compound heterozgosity for Hb S/Hb S-Oman in a one year old female from Oman was reported in 2002.1 The pathophysiology of the sickle syndrome in this compound heterozygote patient must be the result of interaction between HbS and HbS-Oman, the sickle mutation (β6Val) favouring sickling and the O-Arab mutation (β121Lys) favouring haemolysis and changes in red blood cell shape.5 It is important to note that such patients who are compound heterozygotes for Hb S and Hb S-Oman behave clinically like sickle cell anaemia. Our case, who had frequent admissions to hospital with haemolytic crises and who received nu- merous blood transfusions, fully supports this fact. Our study highlights the importance of reviewing the sickle cell cases in Oman carefully, including those categorised as HbC trait or sickle cell disease (as HbS- Oman behaves as HbC on HPLC). The mother of this patient, who is heterozygous for Hb S-Oman (13%), is clinically asymptomatic. Pub- lished reports state that the clinical manifestations in heterozygous Hb S-Oman are only observed in indi- viduals having more than 20% of Hb S-Oman, whereas individuals with a lower percent of Hb S-Oman (14% and below), and concomitant homozygosity for sin- gle gene deletional alpha thalassaemia, are clinically asymptomatic, and have only slight to moderate red blood cell changes.3 Thus both exploration of alpha thalassaemia and family studies will be useful in pre- dicting the clinical outcome. Figure 1: Smear showing Napoleon hat x-shaped red blood cells, characteristic of red blood cells contain- ing HbS Oman 346 S U R E S H VE N U G O PA L , A L P H O N S A S H A J U, S U C H ATA D H U R I , TH U R A I YA A L - H A R T H Y A N D K H A L I D B J A B A L C O N C L U S I O N A patient who has compound heterozygosity for Hb S and Hb S-Oman behaves clinically like a case of sickle cell anaemia. An awareness of existence of Hb S-Oman, an eye for Napoleon hat x-shaped cells on blood film, a review with HPLC in all cases of known sickle cell anaemias, along with family studies, is rec- ommended to unearth cases of Hb S-Oman. R E F E R E N C E S 1. Jahdhamy R, Makki H, Farrell G, Azzawi S. A Case of compound heterozygosity for Hb S-Oman. Br J Haema- tology 2002; 116:504. 2. Venugopal S, Asila NS, Nafisa MZ, Laitha MN, Math- ew S. Hemoglobin S-Oman Trait – A Sickling Variant. Oman Med J 1999; 1:23-24. 3. Ronald LN, Daar S, Jose R, Sandra MS, Gravell D, Bou- hassira E, et al. Hb S – Oman Heterozygote – A new Dominant Sickle syndrome. Blood 1998; 92:4375-4382. 4. Langdown JV, Williamson D, Knight CB, Rubenstein D, Carrell RW. Br J Haematology 1989; 71: 443-444. 5. Ronald LN, Rajagopal K, Slaheddine F, Jacques E, Na- thalie G, Jose R, et al. The Erythrocyte Effects of Hae- moglobin OARAB. Br J Haematology 1999; 107:516-521.