1048 PHENOTYPIC MANIFESTATIONS OF ATAXIA-TELANGIECTASIA

SIR,-Ataxia-telangiectasia (A.T.) patients show several difphenotypic manifestations, including increases in malignancy,’ elevated alpha-fetoprotein (n.F.r.),2 jsensitivity to mutagenic agents,4-6 progressive cerebellar ataxia, and im-

ferent

deficiencies. It has been suggested that the chroless stable than normal in A.T. patients’ cells,’ and A.T. has therefore been included as one of the chromosomal-breakage syndromes. The increased malignancy in A.T. could perhaps be explained by the observed chromosomal instability ; however, no satisfactory explanation has been offered for the other phenotypic manifestations of this disease. Our observations of enhanced chemical-mutagen sensitivity in cells from A.T. patients,4 together with the reports of radiation sensitivity in vivo5 and in vitro,6 suggest an explanation for the pleiotropy of this disorder.

munological

mosomes are

1. In A.T. patients excessive cell death would be expected to occur in the liver, and most likely other tissues. Since hepatotoxic agents induce liver regeneration, " and this process is accompanied by t.i.1’ BB’nthesis, the observed elevations of A.F.P. in A.T. patients2’can be

explained. 2. A normal immunological response requires cell-division, and the chronic exposure of A.T. patients to environmental mutagens would seriously hinder their ability to respond. In addition to the possible direct effects of cell death on the primary immune response, an elevated A.F.P. would also contribute to a suppression of the immune system.9 3. The cerebellar ataxia and other neurological findings could again be the result of cell death in a tissue with a limited cell-division capacity

and

no

regenerative properties.

Although this explanation for the pleiotropic manifestations A.T. is not of obvious therapeutic value, it does suggest a possible explanation for the precipitating event(s).

of

Department of Medical Genetics, University of Toronto, Medical Sciences Building, Toronto, Ontario M5S 1A8, Canada

D. I. HOAR

EXTENSOR PLANTAR RESPONSES IN HYPOKALÆMIC PERIODIC PARALYSIS

SIR,—We have

patient with hypokalasmic periodic intrigued to find, during one moderparalytic episode, unmistakable extensor bilateral

and

seen a

paralysis, ately severe plantar responses. The responses returned to normal when the attack was ended by giving potassium. We have been unable to find a published record of a similar finding, which is not easy to explain, for hypokalaemia is said not to affect neuronal function. Two eminent neurologists we consulted both suggested that this may have been a pseudo-extensor response due to a difference in the degree of paresis between flexor and extensor muscles of the toes. Similar pseudo-extensor responses can, we understand, occasionally occur in such disorders as poliomyelitis and polyneuropathy. Have any of your readers had experience of this phenomenon in hypokalæmic periodic paralysis, and has anyone another explanation to offer? Plating-efficiency (P.E.) of cells and heterozygotes and controls.

from

ataxia-telangiectasia homozygotes

Department of Medicine, War Memorial Hospital, Wrexham, Clwyd

of symptoms in A.T. patients is progressive and after birth. This suggests the involvement of one or many precipitating events-a pattern reminiscent of xeroderma pigmentosum, where sunlight provides the initial insults. The consequences of an inherent hypersensitivity to mutagens in our environment, fraught with natural and manmade mutagens and carcinogens, would be far-reaching. Individuals with the A.T. genotype under constant exposure to environmental mutagens would progressively lose cells through the lethal action of such agents. In addition to mutagen hypersensitivity, we have observed that A.T. patients’ cells have a reduced plating efficiency (1’.1’.). The distribution of 1’.1’. relative to age for control cultures (95% confidence limits are shown for one), 8 A.T. patients, and 3 heterozygous parents are The

we were

I. AHMED JOHN FORBES

onset

occurs

shown in the figure. It is not known whether the reduced 1’.1’. observed in vitro reflects in any way the ability of A.T. cells to divide in vivo. However, this property, coupled with the mutagen sensitivity, would lead to excessive cell death in A.’r. individuals exposed to environmental mutagens. I feel that excessive cell death can account for many, if not all, of the observed phenotypic manifestations in A.T. For example: 1. 2. 3 4. 5.

German, J. Prog. med Genet 1972, 8, 61. Waldman, T. A., Mclntire, K. R. Lancet, 1972, ii, 1112. Simons, M. J., Hosking, C. S. ibid. 1974, i, 1234 Hoar, D. I., Sargent, P. Unpublished. Cunliffe, P. N., Mann, J. R., Cameron, A. H., Roberts, K. D., Ward, H. W

C. Br. J. Radiol. 1975, 48, 374. 6. Taylor, A. M. R., Harnden, D. G., Arlett, C. F., Harcourt, S. A., A. R., Stevens, S., Bridges, B. A. Unpublished.

Lehmann,

URINALS SOAKED IN DISINFECTANTS

SIR,—Dr Emmerson and Mrs Franks (Aug. 2, p. 232) comthe lack of substantial evidence incriminating contaminated urinals in urinary-tract infection. Our experience may, therefore, be of some interest. During the investigation of an outbreak of urinary-tract and wound infections due to a highly resistant strain of Proteus mirabilis in a male surgical ward, we took samples from the urinals as stored for issue in the ward sluice room. The epidemic strain (as defined by proticine typing, the Diene’s phenomenon, and antibiotic susceptibility pattern) was isolated from several of the urinals sampled. Termination of the outbreak coincided with the elimination of this source of infection (among other less specific measures). Dr Emmerson and Mrs Franks may be interested in the report by McLeod,’O which incriminated the hospital urine bottle and bedpan as reservoirs of infection and recommended the use of 02% hibitane or 2% carbolic acid. ment on

Public Health Laboratory and Department of Microbiology, Central Middlesex Hospital, Park Royal, London NW10 7NS.

D. A. MCSWIGGAN M. S. SHAFI

7. Abelev, G. I. Adv. Cancer Res. 1971, 14, 295. 8. Becker, F. F., Horland, A. A., Shurgin, A., Sell, S. ibid. 1975, 35, 9. Murgita, R. A., Tomasi, T. B., Jr. J. exp. Med. 1975, 141, 269. 10. McLeod, J. W. Lancet, 1958, i, 394.

1510.

Letter: Phenotypic manifestations of ataxia-telangiectasia.

1048 PHENOTYPIC MANIFESTATIONS OF ATAXIA-TELANGIECTASIA SIR,-Ataxia-telangiectasia (A.T.) patients show several difphenotypic manifestations, includi...
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