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Case report

Beta-thalassemia major of late diagnosis revealed by pregnancy: a double atypical observation

Beta-thalassemia major of late diagnosis revealed by pregnancy: a double atypical observation

Fall Seynabou1,&, Niang El Hadji Daouda 1, Touré Awa Oumar2, Ndiaye Fatou Samba Diago1


1Clinical Hematology Department at Dalal Jamm Hospital, Dakar, Senegal, 2Biologic Hematology Department at Aristide Le Dantec Hospital, Dakar, Senegal



&Corresponding author
Fall Seynabou, Clinical Hematology Department at Dalal Jamm Hospital, Dakar, Senegal




The diagnosis of beta thalassemia major is most often made in childhood, the discovery in adults is exceptional. We report an observation of a transfusion-dependent form of beta thalassemia diagnosed following a pathological pregnancy. A 30-year-old patient was being managed for transfusion-refractory anemia following a pregnancy with a 28-week amenorrhea abortion. The patient had anemic syndrome, hemolytic jaundice, splenomegaly and craniofacial dysmorphia. Biology noted microcytic hypochromic anemia with a hemoglobin level of 6.3 g/dl and significant erythroblastosis and an electrophoretic profile of major beta-thalassemia. Radiography of the skull showed cortical hypertrophy with a protrusion of the frontal bone and diffuse osteoporosis. The patient received iron chelation therapy combined with a transfusion regimen of red blood cell concentrate and folic acid. This observation illustrates a double atypia of symptomatic major beta thalassemia with transfusion need discovered late and exceptional spontaneous pregnancy in this field.



Introduction    Down

Beta-thalassemia major is due to the lack of synthesis of the β chains of globin, caused by a genetic mutation in the gene coding for the beta chains of hemoglobin [1]. Clinical diagnosis is most often made between 6 and 24 months [2]. We report the case of a beta thalassemia major of late discovery following pregnancy.



Patient and observation Up    Down

A 30-year-old patient was referred to the Clinical Haematology Department on 18 June 2019 for management of transfusion-refractory anaemia. The questioning noted a recent notion (8 months before the consultation) of pathological pregnancy, in a primigravida, who had anaemia requiring repeated transfusions and a late abortion with an in-utero death at 28 weeks of amenorrhoea. She reports the onset of left hypochondrial gravity during pregnancy. Furthermore, she had no medical and surgical pathological history before her pregnancy and there are no similar cases in her family. His parents are not inbred. On admission the general examination showed a general condition classified WHO 2, a weight of 60 kg for a height of 165cm, a temperature of 37°C; a blood pressure of 100/70mmHg; a pulse of 80 beats/min and a respiratory rate of 18 cycles/min. The patient had a Chauffard's triad which associated an anemic syndrome, conjunctival jaundice with dark urine, non discoloured stools without pruritus of hemolytic appearance and a splenomegaly measuring 15 cm below the left chondral rim without collateral venous circulation. Physical examination also revealed craniofacial dysmorphia with protruding cheekbones and a flat forehead. Peripheral lymph node areas were free, the liver was not palpable, and the rest of the clinical examination was normal.


Biologically, the haemogram showed microcytic hypochromic anaemia (haemoglobin: 6.3 g/dl, mean blood volume: 76.9 fl, mean corpuscular concentration: 29.6 pg, mean corpuscular content: 22.7 g/dl), lymphocyte-dominant hyperleukocytosis (white blood cells: 23.98 G/L, neutrophils: 7.21 G/L, lymphocytes: 12.3 G/L) and normal platelet count at 219 G/L. Examination of the MayGrunwald-Giemsa (MGG) stained blood smear shows a significant erythroblastosis made up of 42% erythroblasts. The biochemical stigmas of hemolysis were indirect hyper bilirubinemia at 21.42 mg/L and increased lactodehydrogenases at 1383 U/L. The haptoglobin wasn't dosed. Ferritinemia was elevated at 1643 ng/ml. Liver analysis indicated mild hepatic cytolysis (ASAT 62 IU/L, ALAT 42.4 IU/L). Fasting blood glucose is normal at 0.98 g/l and creatinine at 4.5mg/l. Hemoglobin electrophoresis (Figure 1) showed a profile in favour of major beta-Thalassemia with HbF 96.3% and Hb A2 3.7%. Radiography of the skull (Figure 2) showed cortical hypertrophy with a protrusion of the frontal bone, rounded focal osteocondensation and diffuse osteoporosis. Abdominal ultrasound showed homogeneous hepato-splenomegaly without indirect signs of portal hypertension. Pre-transfusion investigations noted the presence of irregular agglutinins made by a positive indirect antiglobulin test. Antibody identification has not been performed. HIV, hepatitis B and C serologies were negative. Normal cardiac echocardiography, showed no signs of cardiomyopathy. Therapeutically, the patient received 2 sessions of iron chelating therapy (Deferoxamine 40mg/kg), a weekly compatabilized transfusion regimen of red blood cell concentrates and folic acid (10 mg/day).



Discussion Up    Down

Early revelation of the major form is classic, as published by the authors in patients aged between 6 and 24 months [2]. The late discovery as reported in our 30-year-old patient who was previously asymptomatic remains exceptional. This late presentation was also published by Chang et al. [3] and Bento et al. [4] in patients who were 28 and 21 years old respectively. These authors described signs of β-thalassemia major, which appeared in patients who were previously diagnosed with β-thalassemia trait. The evolution towards this major form is explained by an acquired paternal uniparental isodisomy involving the 11p15.5 chromosomal region [3,4]. The absence of previous medical monitoring and weight-delay in our patient does not formally eliminate a trait β-thalassemia undiagnosed in childhood progressing to a secondary thalassemia major. However, in our patient, the hypothesis of a stable thalassemia major, decompensated by pregnancy, remains more than probable. Pregnancy would result in increased nutritional requirements for the fetus and aggravation of pre-existing anemia, thus making a stable non-transfusion-dependent major thalassemia in a transfusion-dependent form. The bone deformities described by the authors during beta thalassemia major [1,2] were less pronounced, but present in our patient. These morphological disorders were not reported in patients with a thalassemia trait that evolved into the major form [3,4]. In its transfusion-dependent forms, the biological changes are severe. The hemoglobin level is often less than 7g/dl, and is classically microcytic hypochrome [1,2]. The lymphocytosis found in our patient is not uncommon and is thought to be reactive to martial overload [5,6].


The only decompensating factor identified in our patient is the onset of pregnancy. Spontaneous pregnancy is rare during beta-thalassemia major [7] and represents the second particularity in our patient who had no specific management of his pathology. Thalassaemia major often leads to hypofertility due to iron deposits in the endocrine organs, which causes a dysfunction of the hypothalamus-pituitary axis. Thus, designs generally require an ovulation- inducing agent with assisted reproductive technology [7]. Pregnancy in these patients remains a challenge due to chronic anemia, hypogonadotropic hypogonadotropic hypogonadism, and iron chelation therapy [8]. Complications on the product of conception, such as the in utero death described in our patient, are also reported in the literature. This abortion could be related to the lack of adequate management of the pregnancy due to a delay in diagnosis. Other pregnancy complications such as gestational hypertension, intrauterine growth retardation, thrombosis and delivery bleeding [8] were not observed in our patient. The hemodynamic changes related to gestation are at the origin of the transfusion dependence responsible for alloimmunization [9] also observed in our patient. A secondary martial overload should make us fear a cardiac and/or hepatic damage, not found in our observation. These haemosiderin deposits are best assessed by magnetic resonance imaging [10].



Conclusion Up    Down

This observation illustrates an atypical case of symptomatic beta thalassemia major with transfusional need discovered during pregnancy. The challenge remains the early diagnosis of non-transfusion-dependent forms in at-risk families and pregnancy planning to reduce maternal-fetal morbidity and mortality.



Competing interests Up    Down

The authors declare no competing interests.



Authors' contributions Up    Down

All the authors have read and agreed to the final manuscript.



Figures Up    Down

Figure 1: hemoglobin electrophoresis of the patient

Figure 2: radiography of the skull: profile in favour of major beta-thalassemia with cortical hypertrophy, a protrusion of the frontal bone, rounded focal osteocondensation and diffuse osteoporosis



References Up    Down

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