1145

Ph1 CHROMOSOME AND LOSS AND

lead values higher than those of adults. In mothers with sufficiently high copper, however, transplacental lead transfer may not occur, as copper may be protective. This interrelationship of metals is important. As lead is a known abortifacient, the prenatal and infancy period may be more critical and pregnancy wastage greater than thus far calculated.

REAPPEARANCE OF THE Y CHROMOSOME IN ACUTE LYMPHOCYTIC LEUKÆMIA SiR,—The letter by Dr Zankl and his colleagues (Jan. 25, p. 221) prompts us to report another unusual case of loss and subsequent gain of the sex chromosomes in malignancy. A 5-year-old Black boy presented in February, 1974, with splenomegaly and generalised lymphadenopathy. A diagnosis of acute lymphocytic leukaemia (A.L.L.) was made on the basis of microscopic examination and cytochemical reactions (P.A.S. and peroxidase) of the bone-marrow. He was started on chemotherapy with vincristine, prednisone, and asparaginase. Complete

Emory University School of Medicine, 69 Butler Street S.E., Atlanta, Georgia 30303, U.S.A.

remission was accomplished within 6 weeks. He also received prophylactic radiotherapy to the brain and intrathecal methotrexate. Maintenance therapy was followed with methotrexate and 6-mercaptopurine. After the first remission of 3 months’ duration, the patient had several haematological and C.N.S. relapses, which were difficult to control with chemotherapy. In February, 1974, the marrow showed the presence of

2 cell-lines-a normal

1,25-DIHYDROXYCHOLECALCIFEROL IN HYPOPARATHYROIDISM AND PSEUDOHYPOPARATHYROIDISM

SIR,-Russell et al.1 found that small amounts of l,25-(OH)2-Dsand 1 a-OH-D,led to rapid correction of hypocalcmmia in patients with hypoparathyroidism. We have been able to confirm their findings in an 11-year-old girl. The diagnosis of hypoparathyroidism was proved by immunoreactive parathyroid hormone unmeasurable (i.P.T.H.) and normal urinary excretion of 3’,5’-A.M.P. in response to intravenous parathyroid extract. After 0-001 mg. of l,25-(OH)jj-D;, per day by mouth for 10 days,

a 46,XY line In July, 1974, marrow cultures showed the presence of the PhI chromosome in all scored cells. In October, 1974, peripheralblood cultures without phytohaemagglutinin (P.H.A.) revealed 45 chromosomes with PhI in all the metaphases. Quinacrine staining showed absence of the Y chromosome. With P.H.A., about 50% of the scored metaphases had a normal karyotype; however, no cells with PhI chromosome had a Y chromosome. In February, 1975, blood and marrow cultures demonstrated complete reappearance of the Y chromosome in the +Phl cells. Blood-cultures with P.H.A. had maintained a 46,XY chromosome complement. This case is unusual in many respects. The presence of a PhI chromosome in A.L.L. has been reported only once. Two patients with chronic lymphocytic leukaemia subsequently developed Phl-positive chronic myeloid leukaemia (C.M.L.).2 Loss and reappearance of the Y chromosome in association with the PhI chromosome has been reported in many cases of c.M.L. in adults.3 However, to our knowledge this has not been reported in children. The pathogenesis of this phenomenon is unknown and might be related to proliferation and faster ageing of the -Y clone, as suggested by Zankl and his colleagues, resulting eventually in the disappearance of this clone. Another explanation might be greater sensitivity of the -Y clone to treatment. This case will be reported in detail elsewhere.

with

46,XY cell-line and

Philadelphia chromosome (Ph).

This work

serum-calcium increased from 6.6 to 9-4 mg. per 100 ml. She was kept on a normal hospital diet without calcium supplement. The effect of 1,25-(OH)2-Da faded slowly within 4 weeks. At that time moderate hypocalcsmic symptoms reappeared (serum-calcium 8-1 mg. per 100 ml.). When she was treated with 0-00025 mg. of 1,25-(OH)2-Da daily (a quarter of the previous daily dose) hypocalcsemia persisted, but serum-calcium did not decrease further. The same daily dose of 0-00025 mg., given after normocalcaemia was restored with 0-001 mg. per day, was too small to maintain normocalcaemia. Thus, 0-001 mg. of l,25-(OH)jj-Dj, seems to be the minimum therapeutic dose to achieve and maintain normocalcaemia in hypopara-

thyroidism. A 9-year-old girl with pseudohypoparathyroidism (classical physical stigmata, very high i.P.T.H., and defective excretion of urinary 3’,5’-A.M.P. after intravenous P.T.E.) was submitted to a therapeutic trial with 1,25-(OH)2Da. 15 daily doses of 0-001 mg. were given, surprisingly without any effect on serum-calcium or serum-phosphorus. We are unable to explain the different responses of the conditions to the active metabolite. It has been suggested that in hypoparathyroidism production of 1,25-(OH)2-Da is defective .2-5 This defect could be due either directly to the lack of endogenous P.T.H.

two

aided by grants from the American Cancer and National Institutes of Health (GM19100).

was

Society (lM-28)

R. SCHMIDT H. DAR M. SANTORINEOU I. SEKINE.

Department of Pediatrics, Albert Einstein College of

NAOMI BAUMSLAG.

indirectly to raised plasma and possibly intracellular phosphorus levels.6 If inorganic-phosphorus concentration U.S.A. is the one important compound triggering l,25-(OH)jjD synthesis, the production of the active metabolite would be impaired not only in hypoparathyroidism but also in pseudohypoparathyroidism, irrespective of the presence LEAD POISONING of high i.P.T.H. Unresponsiveness to 1,25-(OH)2-D3 in pseudohypoparathyroidism therefore remains unexplained. SIR,-Landrigan et al. (March 29, p. 708) must be on the focus of lead from Measurements of circulating l,25-(OHii-Dg) may help congratulated moving poisoning the individual pica-eater to a community-based problem to answer this question and provide further insight in caused by industrial pollution. In children from high-risk . the pathophysiology of pseudohypoparathyroidism. lead areas pica was not a constant finding, but in most 1. Russell, R. G. G., Smith, R., Walton, R. J., Preston, C., Basson, R., families4 hair-lead levels were high in all members. The Henderson, R. G., Norman, A. W. Lancet, 1974, ii, 14. highest levels were in the youngest children. Transplacental 2. Garabedian, M., Holick, M. F., DeLuca, H. F., Brogle, I. T. Medicine,

Bronx, New York 10461,

or

.

transfer of lead does occur.5 and

some

newborns have hair-

Propp, S., Lizzi, F. A. Blood, 1970, 36, 353. Whang-Peng, J., Gralnick, H. R., Johnson, R. E., Lee, E. C., Lear, A. ibid. 1974, 43, 332. 3. Lawler, S. D., Lobb, D. S., Wiltshaw, E. Br. J. Hœmat. 1974, 27, 1. 2.

247.

4. 5.

Klauder, D., Baumslag, N., Petering, H. Unpublished. Baumslag, N., et al. Archs envir. Hlth, 1974, 29, 186.

Proc. natn. Acad. Sci. U.S.A. 1972, 69, 1673. 3. Rasmussen, H., Wong, M., Bile, D., Goodman, D. B. P. J. clin. Invest. 1972, 51, 2502. 4. Fraser, D. R., Kodicek, E. Nature New Biol. 1973, 241, 163. 5. Galante, L., MacAuley, S. J., Colston, K. W., MacIntyre, I.

Lancet, 1972, i, 985. 6. Tanaka, Y., DeLuca, H. F. Archs Biochem. Biophys. 1973, 154, 566. 7. Brumbaugh, P. F., Haussler, D. H., Dressler, R., Haussler, M. R. Science, 1974, 183, 1089.

Letter: Lead poisoning.

1145 Ph1 CHROMOSOME AND LOSS AND lead values higher than those of adults. In mothers with sufficiently high copper, however, transplacental lead tra...
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