Indian Pediatrics 1999; 36:504-506 

Scurvey in Transfusion Dependent Beta-Thalassemia

The basic abnormality associated with thalassemia syndrome is a defect in synthesis of β globin chains. Consequently, there is precipitation of excess a chains leading to reduced red cell survivial, increased production of fetal hemoglobin and ineffective erythropoiesis(1). Patients with beta thalassemia require regular packed red cell transfusions to maintain hemoglobin at optimum levels and to sustain life. A chronic iron overloaded state ensues(2). This may in turn interfere with the ascorbic acid metabolism in the body which may occasionally manifest as scurvy(3). The purpose of this brief communicatin is to focus on this unusual complication in a child with transfusion dependent beta-thalassemia.

Case Report

A 10-year-old boy was diagnosed to have thalassemia major at the age of 9 months. He had been receiving red cell transfusions every 3-4 weeks since then. His transfusion require- ments had increased in the preceding year during which he required two units of packed red cells fortnightly. He had not received any iron chelation therapy because of financial con- straints. He was referred to us when he developed a reddish punctate rash over both lower limbs, back and buttocks. This was associated with pain and swelling of the right thigh. He was unable to bear weight on his limbs and was confined to bed in the week prior to re- porting to our Institute. There was no history of fever or trauma. A history of gum bleeds off and on in the preceding 4-6 months was elicited. Dietary history revealed a grossly in- adequate intake in terms of calories and proteins. The intake of fresh fruits was negligible. Examination revealed an irritable, anxious, afebrile patient with moderate pallor. Anthropometric assessment confirmed that he was stunted and malnourished. There was generalized tenderness particularly in the lower limbs. The pain precluded weight bearing. The right thigh had an indurated, tender swelling over the anterior aspect. The skin over the arms, back, buttocks and legs showed follicular hyperkeratosis with cork screwing of hairs. Perifollicular hemorrhages were present (Fig. 1). The gums were swollen and bled on touch. Apart from hepatosplenomegaly, the systemic examination was un-remarkable.

Investigations revealed a hemoglobin of 6.2 g/dl, TLC of 4600/mm³ with a normal differential count. The platelet count was 1.01x109/L. The prothrombin time and activated partial thromboplastin time were within normal limits. X-ray of the knees showed thin pencilline cortex. The epiphysis was sharply outlined. An irregular thickened white line of Frenkel was also evident at the metaphyseal end (Fig. 2). A skiagram of the chest revealed cardiomegaly. The echocardiography showed left ventricular hypertrophy with reduced left ventricular function. The serum ferritin was 1503 ng/ml. Skin biopsy did not reveal any evidence of graft versus host disease.

 

Fig. 1. Perifollicular Hemorrhages on the anterior aspect of both thights.

 

Fig. 2. X-ray of the knees showing thin pencil-line cortex of bones with irregular thickened white line of Frenkel (arrows) at the meta- physeal ends.

 


The child was diagnosed to have scurvy on the basis of clinical signs as well as radio- graphic evidence. He was administered two units of packed red cells and was started on 200 mg vitamin C daily. Citrus fruits were introduced in his dietary regimen. Oral iron chelation therapy was initiated.

The response to therapy was dramatic. Gum bleeding became passive within a day. Pain in the limbs decreased and he became mobile on the fourth day of starting therapy. The child was examined after a fortnight in the follow-up clinic.

The skin lesions had also healed. There has been no recurrence of symptoms in the five months that he has been in our care.

Discussion

The effects of iron overload on ascorbic acid metabolism were first observed in Bantu males of South Africa who consumed home brewed alcoholic beverages. Scurvy was common in these subjects particularly at the end of winter or in early spring when dietary intakes of ascorbic acid were low(4,5). It has been suggested that persons with siderosis, living on a borderline diet, may manifest features of clinical scurvy as a result of irreversible oxidation of available ascorbic acid by excessive deposits of ferric iron(6).

Wapnick et al. established that patients with transfusion siderosis exhibited a similar type of altered ascorbic acid metabolism as had been documented in the Bantu population(7). They found considerably low leuko- cyte and platelet ascorbic acid concentrations in thalassemics. Oral administration of ascorbic acid resulted in excretion of oxalic acid in the urine. In their study, none of the patients showed clinical evidence of scurvy because of the consumption of a good quality diet(7).

Should then vitamin Csupplementation be a routine in thalassemics? The potential risks need due consideration. In iron overloaded thalassemics, iron is stored in the reticuloen-dothelial cells as ferritin. The chances of iron toxicity are, thereby, reduced. When vitamin C is administered alongwith Desferal, it increases the urinary iron excretion either by liberating iron from stores or by reducing the ferric to ferrous intermediates(8). High doses of vitamin C (500 mg) have been incriminated in cardiotoxicity which manifests as arrhythmia and/or decreased ventricular contractility. Cardiac toxicity is believed to be secondary to the vitamin C induced free iron radical release from the iron stores(9). These in turn, damage the cell membranes by lipid oxidation. Supplementation of vitamin C should therefore be reserved for established states of depletion and only during treatment with iron chelators (10).

A well balanced diet that includes citrus fruits eliminates the need for routine supplementation of vitamin C in thalassemics. Vitamin C therapy, in low doses (100-200 mg) is indicated in those cases with manifest scurvy and for facilitating urinary excretion of iron in conjunction with iron chelation therapy. Children who have insufficient access to citrus fruits could also be prescribed low dose vitamin C therapy.

 

 References