Macrocytosis and Down's Syndrome

DEAR SIR, We reported macrocytosis in 92 adult Down's syndrome patients (MCV 102.5Â±7.87fi), the MCV having been calculated from separate red cell counts (Model D Coulter counter) and microhaematocrit estimations (Eastham and Jancar, 1970). No signifi cant sex difference was found. Using a Coulter-S-Plus electronic cell counter, we have now found the MCV in 16 male and 17female adult Down's syndrome patients to be 96. 3Â±3.79 fi (1 SD), again with no sex difference, and with an RDW of 10. 68Â±1.67. (The normal RDW of about 10 indicates no abnormal anisocytosis). These patients were not being treated with anticonvulsants and were not anaemic. This latest result is significantly smaller than our earlier result (t test, P 0.001), and almost certainly reflects the change in technological method, but the mean value for the MCV is still above the accepted upper limit of the normal range (95 fi). The earlier method included centrifugation of red cells with associated plasma trapping, while the current method measures the MCV directly and eliminates the effects of plasma trapping. The explanation for macrocytosis in Down's syndrome is still unknown, but it has been shown that the red cell envelope in trisomy Down's 1974). The syndrome is characterized by severe extrapyramidal symptoms of muscular rigidity and akinesia, with hyperpyrexia, fluctuation in the level of consciousness and autonomic dysfunction, which in cludes tachycardia, labile blood pressure, hyper ventilation, profuse diaphoresis, sialorrhoea, dysarthria and dysphagia. The patient may be alert, but mute, with other catatonic symptoms, progressing to stupor and coma in severe cases. The syndrome may develop within hours of initial drug exposure, or after months of drug use, and occurs at therapeutic rather than toxic dosage. Once started, the syndrome develops rapidly over the next 24â€”72 hours, and if neuroleptic medication is not stopped the outcome may be fatal. A mortality rate of 20 per cent has been reported (Cardoff, 1980). Cardio-respiratory collapse is the usual mode of death, and there is no specific treatment, apart from supportive measures. There are no specific or diagnostic laboratory findings in the NMS, but there may be a polymorphonuclear leucocytosis, abnormal liver func tion tests, and elevated serum CPK, probably caused by myonecrosis after prolonged skeletal muscle con traction (Smego and Durack, 1982). The EEG is generally normal, but may show non-specific slow activity. Examination of Ã§SF,isotope brain scans and Cr scanswhereperformedhavebeennormal(Caroff, 1980), and post mortem findings have been negative. The disorder may be mis-diagnosed as encephalitis or other infectious diseases of the CNS. The NMS has been compared to acute lethal catatonia described by Stauder (1934) many years before the advent of neuroleptics, and to the syndrome of malignant hyperthermia associated with general anaesthetics. Heat stroke which may occur in patients receiving phenothiazines and butyrophenones can be distin guished from the NMS by the lack of muscular rigidity. Although the pathogenesis of the NMS is unknown, it has been suggested that features of the syndrome can be explained by dopamine-receptor blockade in the basal ganglia and hypothalamus. It is not known why some individuals are susceptible to the NMS, but there havebeensome casereports ofpre-existing or anic braindisease (Meltzer, 1973)orphysical exhaustion anddehydration (Itohetal,1977). Itisinteresting that some patients have been safely re-exposed to the same neuroleptic without recurrence of the syndrome. Having recently seen a case with fatal consequences (Cope and Gregg, 1983), I hope that this brief summary of the condition will lead to more widespread recognition.