Middle East Journal of Family Medicine

ABSTRACT

Background and objectives: Thalassemia or hemoglobinopathy is a hereditary disease caused by defective globin synthesis resulting in abnormal as well as decreased quantity of globin chains. Ineffective erythropoiesis, hemolysis, and increased red blood cell turnover.

The present study deals with the effects of ß-thalassemia on the following serum biochemical parameters (sodium, potassium, calcium, phosphate and uric acid).

Material and method: A prospective study was carried out from September 2004 to March 2005 by collaboration between clinical biochemistry and pediatric departments in College of Medicine, Hawler Medical University on thirty patients with ß-thalassemia in comparison with thirty normal subjects.

Results: The results showed that there was a significant difference (P< 0.05) in the level of serum Potassium, Calcium, Uric acid and hemoglobin while the differences in sodium and phosphate were not significant.

Conclusion: Based on findings of the present study it can be concluded that ß-thalassemia causes multiple abnormalities in biochemical parameters.

The thalassemia syndrome is a group of metabolic inherited disorders⁽¹⁾ characterized by microcytic hypochromic red blood cells. The homozygous state, thalassemia major results in a severe anemia and often death before puberty. The heterozygous state, thalassemia minor is less severe and may be asymptomatic with little or no anemia^(2,3).

The word thalassemia comes from the Greek "thalassa", sea referring to thr Mediterranean and "haima", blood which means blood disease of the sea^(3,4,5). The first description of severe thalassemia as a unique disorder was described in 1925 by a Detroit pediatrician "Thomas Cooley" who described a severe type of anemia in children of Italian origin which was later named after him⁽³⁾.

Thalassemia represents the most common single gene disorder causing a major public health problem⁽⁶⁾.

It is widely distributed through the Mediterranean, Middle East, India, southeast Asia and Africa⁽⁵⁾. Iraq is one of the countries in which 6-10% of the population have hemoglobinopathy of which thalassemia is a major part⁽⁷⁾.

The underlying abnormality in the thalassemia syndromes is thought to be absence or reduction in production of hemoglobin⁽²⁾.

There are 2 types of thalassemia - alpha and beta depending on which globin chain is affected by genetic mutation or deletion⁽⁸⁾.

The disease is called beta thalassemia when ß chain production is decreased relative to alpha chain production and alpha thalassemia when a chain production is decreased relative to ß^(2,6).

Over the last 3 decades the development of regular transfusion therapy and iron chelating has dramatically improved the quality of life however in the developing world, poor availability of proper medical care, and safe and adequate red blood cell transfusion, together with poor compliance to chelation therapy remains a major obstacle. Despite the increased life expectancy thalassemia complications keep arising especially iron overload related complications as well as toxicities of iron chelator⁽⁹⁾ which may result in metabolic and endocrine abnormalities like hypogonadism, diabetes mellitus, hypothyroidism, hypo-parathyroidism and zinc and copper deficiency^(10,11,12).

Precipitation of alpha globin chains in the thalassemia RBC may interfere with normal membrane function leading to increased calcium content which is more pronounced in splenectomy patients correlates with the degree of anemia⁽¹¹⁾.

1- Subjects
This study was conducted on 60 individuals all under 17 years, thirty 30 of whom were patients with ß-thalassemia and the other thirty 30 were healthy controls.

ß-Thalassemic patients in Erbil were all registered in a pediatric hospital thalassemic unit to receive treatment. The diagnosis of thalassemia was based on hematological criteria (peripheral blood evaluation and hemoglobin electrophoresis of the patients from early years of life. The mean ± S.E of age was 11.93±1.1 years and the range 1-16 years. While the healthy individuals mean ±S.E of age was 12.2±1.1 years and the range 1-17 years - see Table 1.

2-Blood sample collection:
Three to five millilitres of venous blood was drawn from ß-thalassemic patients and healthy individuals., Collected blood was left standing at room temperature until it clotted, then the sample centrifuged at 300 rpm for 10 minutes for removal of serum from suspended cells. Then the serum was tested for sodium, potassium, calcium, phosphorous and uric acid determination.

3-3- Instruments
1- Spectrophotometer (Spectronic 21)
2- Centrifuge type Labofuge 200
3- Computer for data analysis
4- Flame photometer (Jenway)

4-Method
Sodium and potassium in Serum was measured by an instrument called a Flame photometer according to Varly⁽¹³⁾ method as follows:

Principle of operation (Flame photometry):-
Flame photometry relies upon the fact that the compounds of the alkaline earth metals can be thermally dissociated in a flame and that some atoms produced will be further excited to a high energy level. .When the atoms return to ground state they emit radiation which lies mainly in the visible region of the spectrum (each element emits radiation at a wave length specific to that element⁽¹³⁾ while routine biochemical tests were done in serum for phosphorous determination according to Gomorri methods⁽¹⁴⁾.

Serum uric acid and calcium was determined for both groups by an enzymatic colorimetry method by using ready made kits Biomerieux Sa. (France) according to the method of (Barhand and Coms) respectively^(15,16).

5-Statistical evaluation
Statistical analyses were carried out by using some statistical measurements. Biochemical values were presented as the mean±S.EM and range. All analyses for difference between the two independent groups were performed by Student's t tests, with a level of significance assigned at 0.05. Values less than 0.05 (P<0.05) were considered to indicate statistical significance⁽¹⁷⁾.

Group I ( Healthy individuals ):
The mean±S.E for serum Potassium gave values of 4.8±0.1 mmol/L and a range of 3.2-6.4 mmol/L. The mean±S.E for serum Sodium was 139±1.5 mmol/L and the range was 122-150 mmol/L. The mean±S.E values for Calcium, Phosphorous and Uric acid were 11.3±0.3, 4.8±0.3 and 4.6±0.2 mg/dl respectively, with the range of 8.7-15, 1.1-8 and 2.8-8.6 mg/dl respectively as shown in Table 1.

Group II (ß-thalassemic patients):
The mean for serum Potassium gave values of 5.3±0.2 mmol/L and a range of 3.6-7.5. The mean for serum Sodium was 141±1.6 and the range was 122-159 mmol/L. The mean value for Calcium, Phosphorous and Uric acid were 46±0.2, 5.6±0.3 and 5.9±0.3 mg/dl respectively, with the range of 2.4-6.6, 3.5-9.4 and 3.8-91 mg/dl respectively as shown in Table 2.

In comparison between healthy individuals and ß-thalassemiac individuals, it was showed significant differences in serum Potassium ,Calcium, Uric acid and Hb while serum phosphorous and sodium showed no significance - see Table 2 Figure 1 and Figure2.

The goal of the present study was to understand the effects of ß-thalassemia on certain serum biochemical parameters (Sodium, potassium, calcium, phosphate and uric acid).

The aim of transfusion is to maintain a hemoglobin level that inhibits ineffective erythropoiesis, marrow expansion and allow normal growth. The hemoglobin should be maintained between 10-14 gm/dl with pre-transfusion hemoglobin of 10-11 gm/dl. Most patients in the present study were suboptimally blood-transfused thalassemics. They had significant anemia of 7.5±0.2g/dl which resulted in growth retardation, delayed puberty, and retarded bone age. These findings were in agreement with the previous studies^(1,18,19).

The results obtained in this study as noted earlier showed that the mean value [Mean±S.E.] of serum Potassium for ß-thalassemiac patients was 5.3±0.2 mmol/L. The mean value for Uric acid was 5.9±0.3 mg/dl. The values were significantly higher in ß-thalassemiac patients compared with the control group (p<0.05) which is in accordance with Kostas et al⁽²⁰⁾.

Increased hemolysis and/or red cell turnover might be blamed for the elevated serum potassium and uric acid levels. Highest normal value of uric acid in the beta-thalassemic patients, despite the increased red cell turnover could be due to the increased excretion of uric acid, evidenced by the high fractional excretion in uric acid, which may be the result of the supra normal proximal tubular function⁽²¹⁾.

Aldosterone is a mineralo-corticoid which acts on P cells of the distal tubule and causes Na + reabsorption in exchange for K+ or H+ secretion. This defect in potassium secretion is not clinically apparent under normal circumstances, though hyperkalemia is likely to manifest with mild degrees of renal impairment⁽²²⁾. This might explain the slight elevation of potassium to upper normal range in our study.

Furthermore, there was also a statistically significant difference in serum calcium between the control grouip and ß-thalassemiac patients. The same observation for calcium level was also reported by Saka et al⁽²³⁾.

On the other hand a non-significant increase in the mean levels of serum phosphorous was found in patients with ß-thalassemia compared to the control group, This finding is similar to that found by Kostas et al⁽²⁰⁾.

The ß-thalassemia major results in severe anemia, which needs regular blood transfusion. The combination of transfusion and chelating therapy has dramatically extended the life expectancy of thalassemic patients^(22,23). On the other hand, frequent blood transfusion in turn can lead to iron overload^(24,25).

Hypocalcaemia is a well known complication of iron overload⁽²⁶⁾. Iron overload occurs either from the transfusion of red blood cells or because there is increased absorption of iron from the digestive tract. Both of these occur in thalassemia. Iron overload also causes pituitary damage with hypogonadism, endocrine complication, hypothyroidism and hypoparathyroidism is also seen⁽²⁷⁾
Parathyroid hormone which is secreted by the parathyroid gland mobilizes calcium from bone^(27,28).

A study done by Desanctis 1995 showed that hypocalcemia due to hypoparathyroidism is recognized as a later complication (age 16 year and above) although in our study hypocalcemia was observed in a very younger age. This could be attributed to poor patient compliance due to poor education about the disease. An iron chelating agent with its pump is not always available, and communications between the thalassaemic centers and the patients are not always easy.