Mitochondrial myopathy presenting as ataxia with dilated cardiomyopathy.

Mitochondrial disorders are multisystem diseases with very heterogeneous clinical manifestations. Common cardiac features include cardiomyopathy and conduction defects. We report a five-year-old boy who presented with signs of congestive cardiac failure and was diagnosed to have dilated cardiomyopathy. Six months later, he developed progressively worsening ataxia, hypotonia, other cerebellar signs, hearing loss, severe sensory peripheral neuropathy and lactic acidosis. Electronmicroscopy of skeletal muscle biopsy was consistent with mitochondrial myopathy.

Transferrin receptor expression by blast cells in acute lymphoblastic leukemia correlates with white cell count & immunophenotype.

Transferrin receptor (TR) expression by blast cells in 127 cases of acute lymphoblastic leukemia (ALL) at presentation and 19 cases at relapse was examined using three anti-TR monoclonal antibodies to find its correlation with prognostic features such as the total leucocyte count (TLC), the morphology of blast cells and their cytochemical and immunophenotypic properties, as well as age and sex of the patients. Blasts in 62 per cent of thymic (T) ALL cases at presentation showed significant TR expression as compared to only 10.9 per cent in common ALL (CALL) (P < 0.001). This differential expression of TR was also observed among cases with > 50 x 10(9)/l TLC, while in cases with < 50 x 10(9)/ l TLC no such pattern was observed (30% TR positivity in T-ALL vs 20% TR positivity in non-T-ALL). Furthermore, the percentage of TR positive blasts was significantly higher (P < 0.005) in cases with > 50 x 10(9)/l TLC as compared to those with < 50 x 10(9)/l (48.3-54.4% vs 24.9-28.8%). In contrast to CALL cases at presentation, those at relapse showed a very high TR positivity (54-66%), similar to the T-ALL cases (53-84%). This suggests a high proliferative rate of blast cells in ALL at relapse, irrespective of its immunophenotype. There was no correlation of TR expression with blast cell morphology (FAB L1 vs L2), their cytochemical properties and sex of the patients. However, a significantly higher incidence of TR positivity was observed in patients above 10 yr of age compared to those below 10 yr (47% vs 15%; P < 0.001). The incidence of T-ALL was also significantly higher in the former group (56%) compared to the latter (33%) (P < 0.005). Our data suggest that by virtue of its association with features of poor prognosis, e.g., age above 10 yr, expression of thymic markers, high leucocyte count and disease relapse, TR expression by blast cells in ALL could serve as a biological marker of poor prognosis.

Red cell distribution width as a measure of severity of iron deficiency in iron deficiency anaemia.

Of the various red cell parameters used for distinguishing iron deficiency anaemia (IDA) from beta-thalassaemia trait BTT, red cell distribution width (RDW), which is an objective measure of the degree of anisocytosis, was examined by us for its discriminating value. RDW was measured in 55 patients of IDA and 56 patients of BTT at presentation with the help of an automated haematology analyser. The mean RDWs in IDA and BTT patients were 18.2 +/- 3.8 and 15.1 +/- 1.2 respectively (P < 0.001). In IDA, RDW showed an inverse relationship with the haemoglobin level (r = -0.543; P < 0.001), while no such correlation was observed in BTT patients. An inverse relation was also observed in IDA between RDW and transferrin saturation (TS). Patients with high RDW had low TS and vice versa. The latter finding, although statistically not significant, suggested that the degree of elevation of RDW in IDA could reflect the severity of iron deficiency. Our study revealed that red cell count, which was significantly higher in BTT patients (P < 0.001), the RDW, and the discriminant function (DF) calculated from these two parameters could be useful in distinguishing IDA from BTT. A RDW above 17.1 strongly suggests the presence of IDA. For RDW below 17.1 the DF can be applied for further discrimination. RDW has the advantage of being obtained directly from the analyser, while DF is a calculated value.

Effect of hydroxyurea on foetal haemoglobin in myeloproliferative & myelodysplastic syndromes.

The effect of hydroxyurea on foetal haemoglobin (HbF) levels was evaluated in 36 patients of myeloproliferative and myelodysplastic disorders. In 17 (47.2%) patients, HbF levels increased from 1.40 +/- 1.17 to 3.03 +/- 1.97 per cent after 4 wk therapy with hydroxyurea. In the responders this increase was highly significant (P less than 0.001). The rise in the HbF levels after hydroxyurea therapy was significant in patients with chronic myeloid leukaemia but not in the other groups.

Limitations of the therapeutic regimens for myelodysplastic syndrome.

Thirty patients of myelodysplastic syndrome (MDS) were treated over a period of 2 yr using 3 different treatment regimens. Twelve patients received hydroxyurea, 4 were given low dose cytosine arabinoside and 14 others were treated with an aggressive acute myeloid leukaemia (AML) induction regimen. A low complete remission was obtained in the first 2 groups (17 and 25% respectively), whereas 9 (64%) patients attained complete remission with the AML induction regimen. Remission in the latter group was associated with prolonged and severe pancytopenia requiring intensive support. Patients in all the 3 groups had a short duration of remission culminating in death with progressive marrow failure or evolution to AML, indicating the limitations of the current treatment strategies for MDS and highlighting the need for exploring newer therapeutic approaches.