Amino-acid tolerance curves and amino-aciduria in Cooley's and sicklecell anaemias.

This study was prompted by the previous finding of amino-aciduria (Choremis, Zannos, and Basti, 1957) and qualitative and quantitative changes of serum proteins in thalassaemia and sickle-cell anaemia (Allamanis, 1955; Afentaki, 1949; Minnich, Na-Nakorn, Chongchareonsuk, and Kochaseni, 1954). The electrophoretic pattern shows a fall in albumin, a moderate fall in the a, a29 and I globulin fractions and an increase in the -y globulin fraction (Allamanis, 1955). In some cases liver function tests (thymol turbidity and cephalin-cholesterol flocculation tests) are positive (Choremis and Kyriakidou, 1954; Minnich et al., 1954). This abnormal electrophoretic pattern, and especially the increase in y globulin, does not necessarily indicate liver damage, although this may occur. In order to elucidate further the amino-acid metabolism in Cooley's and sickle-cell anaemia total plasma amino-acids and urine paper chromatography studies for amino-acids were undertaken after oral administration of protein and protein hydrolysate, as well as after intravenous injection of amino-acids. In this way the proteolytic activity of the gastro-intestinal tract, the absorption of amino-acids, their intermediate metabolism and their rate of disappearance from the blood stream, and especially their excretion through the kidneys, were studied. There are no references in the available literature to any study on the metabolism of amino-acids in thalassaemia and sickle-cell anaemia. In a previous paper, the above observations stimulated an investigation of another aspect of protein metabolism in these anaemias, namely, the amino-acids in blood serum and their excretion in the urine (Choremis et al., 1957). A few reports have appeared, however, dealing with aminoaciduria in other types of anaemia. Souchon and Grunau (1952) described one case of congenital spherocytic anaemia and cholelithiasis with amino-aciduria which was considered to be due both to liver damage and to faulty reabsorption by the tubules. Weaver and Neill (1954) reported five cases of pernicious anaemia with abnormal excretion of taurine and some overexcretion of lysine, leucine, and cystine. This type of aminoaciduria was attributed to lack of vitamin B12 which is known to be involved in methyl synthesis and transmethylation of certain amino-acids. The same authors also reported five cases of other varieties of anaemia without any pathological findings. Pare and Sandler (1954) described 12 cases of March haemoglobinuria with aminoaciduria. In the above cases the renal tubular defect was considered to be the cause of the abnormal amino-aciduria (overexcretion of cystine in all cases and of 83-amino-isobutyric acid in 11 of the 12 cases).