Thalassaemia and sickle cell disease (SCD) are the most widely distributed blood genetic disorders that occur at a high frequency in some populations including the Mediterranean region, parts of the Middle East, South East Asia and the Indian subcontinent. It is estimated that thalassaemia major affects 100,000 newborn every year world-wide. The high incidence of these chronic haemolytic diseases in developing countries poses a high load on the national economy because of the expensive treatment protocols and the considerably high morbidity rates of these patients. Repeated blood transfusion to keep haemoglobin above an acceptable level requires well-equipped blood banks with expensive facilities to screen, store and manipulate blood and blood products. Iron chelation therapy is an essential part of treatment to avoid or delay the deleterious effects of iron overload on different organs including the liver, heart, pancreas and endocrine glands. This inquires injecting deferoxamine subcutaneously for 12 hours daily with a special pump. Both deferoxamine and pumps are expensive and therefore not accessible for all patients.
In developing countries, the majority of transfusion-dependent patients with chronic haemolytic anaemia (thalassaemia and SCD) suffer from the consequences of sub-optimal treatment. The mortality rate is still high and usually patients die before the age of 30 years. They also suffer from chronic multi-organ damage including cardiac failure, liver cirrhosis, insulin-dependent diabetes mellitus, growth and pubertal failure and many skeletal abnormalities and fractures. In developed countries the introduction of high transfusion regimes and efficient chelation therapy improved survival rates and prevented cardiac and hepatic damage. However, a majority of thalassaemic patients still have significant growth and pubertal abnormalities, bone disease and multiple endocrine disorders.
In Egypt the incidence of thalassaemia major ranges between 0.1 - 0.2% which gives very high patient load on the medical services. In our University of Alexandria Children's Hospital, Alexandria, Egypt. The Haematology clinic has an average of 150 thalassaemic children registered. The same problem is encountered by me in the Royal Hospital, Muscat, Oman, with high prevalence of SCD and thalassaemia and suboptimal treatment. Because of the restricted economic resources, both hospitals adopt a low transfusion therapy (to keep haemoglobin above 9 g/dl) with IM chelation 3 times per week. With this form of sub-optimal treatment we observed that a large number of our thalassaemic children have severe growth and pubertal failure/delay, beside other hepatic, cardiac and skeletal abnormalities. In fact they constitute 40% of patients attending our Endocrinology clinic. This stimulated me to perform an extensive study to survey growth and pubertal development in theses patients (study-1) and investigate the different factors that might affect their growth and pubertal development (studies 4 through 10) a \veU as bone mass density (studies > 1,12). The frequent involvement of the liver in these patients led us to study some hepatic functions and the prevalence of transfusion-associated hepatitis B surface antigenaemia and hepatitis-C virus antibody scropositivity in relation to their linear growth (studies 2,3). We studied the nutritional intake of these patients, their intestinal absorption of D-Xylosc and 48-h stool fat content in relation to their body mass index, subcutaneous 'at thickness and mid-arm circumference (studies 4,5,9).
Their defective linear growth urged us to investigate their growth hormone (GH) secretion (spontaneous nocturnal as well as after provocation) and insulin-like growth factor-I (IGF-I) and IGK-binding protein-3 (IGKBl'3) concentrations. Our findings demonstrated high prevalence of defective GH secretion in these children that necessitated imaging of their hypothalamic pituitary area. Imaging studies revealed original data about structural abnormalities in the anterior pituitary gland, different degrees of pituitary atrophy and empty sella and infiltration the gland as well as the mid-brain by hacniosidrin in thalassaemic children, the mechanism of these findings was explained (studies 4-6,10). Because of their slow growth, the presence of abnormal GH/IGF-I/BP3 axis, and structural abnormalities of the pituitary gland, the next step dealt with the response of IGF-I to exogenous GH and the clinical response of their linear growth to GH therapy for a year or more (studies 4,9).
Based on the fact that these patients have high prevalence of bone pains and osteoporosis during late childhood and have high risk of spontaneous fracture thereafter, we measured their bone mass density to investigate the relation between the former and the degree of iron load, growth parameters, and different anabolic hormone concentrations in these patients (studies 11,12).
|Date of Award||1998|
- Sickle Cell Disease
- Bone growth
- Bone mineral density
- genetic disorders