PROSOPAGNOSIA

892 conversion factors and tables. Whilst there is general agreement between centres, discrepancies do occur and these are mainly related to the process of rounding off to a significant number of decimal places. Obviously if we are to avoid interlaboratory variation being added to, we must pay attention to uniformity of conversion factors, and we welcome the recent report of the Joint Working Party on Quantities and Units," which gave such a definitive list. However, our consideration of "decimal places should not end here. In the expression of normal ranges " in molar concentration, there is a superficial appearance of contraction for some components and expansion for others (e.g., plasma-urate 0-1-0-4 mmol. per 1.=2-0-7-0 mg. per 100 ml., and serum-bilirubin 5-17 timol. per 1. =0-3-1-0 mg. per 100 ml.). If the former is expressed to only one decimal place, then there is a loss of resolution which may possibly have clinical significance. However, with the latter example we have to make the decision of reporting the result to the nearest mol. per 1. or nearest 10 .mol. per 1.; the former is equivalent to 0-06 mg. per 100 mol., which is beyond the precision of present methods, and the latter to 0-6 mg. per 100 ml., which is a significant change in many clinical conditions. It follows therefore that before we adopt molar concentration, attention must be paid to such rounding procedures and agreement reached nationally. Our final contribution relates to re-education. The pathology departments, which have so far largely brought about this change, have also accepted the responsibility for retraining users. To date there have been published several rather similar papers,11,12 describing the system and its dogma, which usually end by quoting the experience of those centres which have already changed, by recommending the changeover period to be very short. But the clinician wishes to know not only whether a concentration is " normal ", but whether it is significantly different from previous results. If it falls without the " normal range ", he will

the level to dictate therapy. Thus a diabetic blood-glucose of 400 mg. per 100 ml. may be given a quite different dose of insulin to the diabetic with a glucose of 1000 mg. per 100 ml. Therefore the clinician often with

use

a

will need

know more than the normal range in molar concentration, for he will have to readjust his " action limits ". If we are to avoid the situation where results are reported in molar concentration but always converted to more " useful " figures by the user, we must pay more attention to clinical participation in the changeover retraining programme. This has not been documented from centres where the change has been made, and their experience would be invaluable. We welcome most of the Systeme recommendations and feel that their introduction to the medical field is both inevitable and ultimately beneficial. However, we are concerned at the untidy haste with which we are urged to adopt, as yet, partially tried conventions, which carry no immediate advantages. to

Department of Clinical Chemistry, Ninewells Hospital and Medical School, Dundee DD2 1UD.

D. B. WALSH E. SIMPSON.

** * We have rashly changed the abbreviations and decimal points in this letter, which conformed to SI, and replaced them by those ancient ones to which The Lancet still, for the moment, clings.-ED. L. Sir,- have read with interest your correspondence about SI units

over

the past few months and I should like

to

add

Society of Medicine in 1971,1 lignocaine injection continues be dispensed in concentrations expressed as a percentage. Doses are, however, expressed in mg. and I wonder how many members of the medical profession can make an accurate, rapid calculation of the number of mg. in 1 ml. of a 1% solution ? Is it not time that this potentially lethal method of expressing drug concentrations was abandoned ? In correcting an error made by other authors (May 25, p. 1055), Dr Fraser (June 8, p. 1163) points out

to

"

that " mM. per 1. is inadmissible because in SI units M denotes mega and m denotes milli- or meter. However, he missed the more relevant point that mM. per 1. is nonsense whatever the system of units since in pre-SI terms M is the abbreviation of molar which is a concentration and not an " amount: hence the " per 1. is superfluous and incorrect. It will be a sad day for scientific medicine if Dr Hall’s x-m/s calculation (May 18, p. 1006) ever gains acceptance. It certainly removes confusion about units since the resulting figure has no units, but is this not encouraging the

thoughtless ? Another potential

source of danger which is worthy of mention is the abbreviation of microgramme to mcg. The meaning is fairly clear when the abbreviation is printed, as it is in some textbooks, but how many of us have handwriting which is immaculate enough to prevent mcg. from being read as mg. ! Notable difficulties with SI units arise in the case of drugs which are standardised biologically. One such problem has, however, been overcome by a consultant surgeon of my acquaintance who expresses doses of heparin in mg. while his anaesthetist colleagues ponder on the insoluble problem of how many units there are in a mg. The SI system reduces to a minimum the number of units which have to be defined and is thus intended to simplify. Simple systems are the least likely to go wrong, and so there can be no doubt that the SI system should be adopted immediately in medicine for reasons of safety and science, quite apart from its aesthetic appeal. It is only sentimentality and inflexibility which retain the potential dangers, such

as %. 104 Park Avenue

South, London N8 8LS.

J. C. FOREMAN.

PROSOPAGNOSIA SIR,-Your interesting editorial (Aug. 17, p. 388) calls attention to this neglected sign of neurological disease. Since you say that the sign may be less rare than the literature suggests and may have localising value, it is appropriate to mention that prosopagnosia is not a single entity and to add a word on how screening for it should be carried out. A clear distinction should probably be drawn between two different disabilities: non-recognition of familiar faces and non-recognition of unknown faces in general. This separation was not considered in your editorial, but in fact the term prosopagnosia should be reserved for the former. Several authors have even questioned whether the two kinds of deficit are at all related.2-5 The point is relevant because it is highly probable that the two types of disability in face discrimination correspond to different anatomical pictures. Hence, testing should include not only sets of photographs of well-known personalities to be named and matched, but also actual recognition of persons known to the patient, and the standardised test of facial recognition of Benton and Van Allen.3Data collected this way should be published

one or two comments.

Despite 11. 12.

the recommendations

published by the Royal

Baron, D. N., Broughton, P. M. G., Cohen, M., Lansley, T. S., Lewis, S. M., Shinton, N. K. J. clin. Path. 1974, 27, 590. Dybkaer, R. Clin. Biochem. 1969, 2, 227.

Units, Symbols and Abbreviations (edited by G. Ellis). Royal Society of Medicine, London, 1971 2. Warrington, E. K., James, M. Cortex, 1967, 3, 317. 3. Benton, A. L., Van Allen, M. W. ibid. 1968, 4, 344. 4. Benton, A. L., Van Allen, M. W. J. neurol. Sci. 1972, 15, 167. 5. Hécaen, H. Introduction à la Neuropsychologie. Paris, 1972. 1.

893

and would

eventually contribute

to

establishing

a

reliable

anatomical correlation. Language Research Laboratory, Centro de Estudos Egas Moniz, Lisbon Faculty of Medicine,

Portugal.

ANTÓNIO R. DAMÁSIO ALEXANDRE CASTRO-CALDAS.

ANTENATAL DIAGNOSIS OF GENETIC DISEASE

SIR,-Your editorial (Aug. 31, p. 503) hardly reflects the precision in aim, word, and number of the valuable document to which it refers.1 I do not know how you know of the nature of susceptibility to diseases which we are now spared, but this is surely irrelevant, as is the clearly defined genetic nature of most of the disorders manifest in the fetus and capable of detection by amniocentesis. The numbers afflicted are presumably unchanged by the decline in infective disease, although some of the consequences have been made worse for parents by advances in neurosurgery and the practical difficulties in not applying them. Now that the discovery of oc-fetoprotein as a diagnostic aid has made spina bifida, which is the commonest severe and viable fetal disorder, capable of elimination, the convention of regarding most fetuses whose disorders are manifest in amniotic fluid as having genetic diseases is no longer appropriate. The aim of fetal diagnosis, with its attendant risks, anxieties, and dilemmas, is either therapy, which is hardly possible except in rhesus disease, or elimination, which is unacceptable to many women. However, it is certainly acceptable to many whose children have had spina bifida, muscular dystrophy, mongolism, or severe metabolic disorders, such as Hurler’s syndrome. The prevention of fetal disorders, to which you refer, can only be brought about by reducing the number, activity, or effectiveness ot their determinants and this is impossible in most genetical disorders and, in other disorders, such as spina bifida, requires a knowledge of the teratogens. As the bulk of fetal disorders are of unknown aetiology, the prospects of applying knowledge for their prevention seem good, and we may expect the causes of fetal crippling which act today to become as inactive as those which made crippled children a common sight in the last century. Since teratogens are likely to impair those who are not conspicuously afflicted, major benefits in fetal health may be expected to follow their identification. The accolade of prevention should hardly be used either to obscure and sweeten the realities of elimination or to divert resources from the search for teratogens. Most genetic disorders cannot be prevented by counselling, since the majority of parents will not have their potential to produce children revealed until they have had an affected child; only a minority, the second affected children, could have had their conceptions prevented by counselling. The effect of such actions on the gene frequency of the determinants is small. Since prevention is ineffective, and infanticide unacceptable, elimination is at least a rational solution to the very real problems posed to parents who have both a high risk of an affected child and experience of the distress involved. In such cases family planning is an ineffectual euphemism, for the only options within the marriage, apart from selective elimination, are unplanned parenthood or planned unparenthood. The main indications for fetal be:

diagnosis

would

seem to

(1) When a child has already been born with a strongly familial disorder which could be diagnosed in utero and the

The parents consider elimination a reasonable procedure. numerous genetic disbrders manifest in utero are individually rare, the commonest being Hurler’s syndrome, with perhaps 20-40 In cases a year and as many potential high-risk conceptions. Jews Tay-Sachs disease is the commonest with perhaps 5 cases a year in Britain. With such rarity there is a need for the sort of official documentation which the Canadians enjoy if both inefficiency and unreliability are to be minimised. The commonest indication is spina bifida: each year there are some 4000 neuraltube defects, and there could be a demand for almost as many tests for subsequent conceptions. The second commonest indication is trisomic mongolism, in which your editorial asserts the recurrence risk is 1 in 40; the guidelinessay " may be as high as one in a hundred ". The largest prospective series found five out of almost five hundred. The risks are similar to those of the " over-forties ", but the anxieties are likely to be deeper. (2) When a method is available which detects a substantial proportion of afflicted fetuses: an example is the elimination of boys to likely or definite carrier of X-linked diseases. This is well known to hxmophiliacs but the demand is small. The elimination of daughters to haemophiliacs is more efficient, but is rarely considered. The demand in Duchenne’s disorder is somewhat larger, and will become larger when a reliable heterozygote test is available. High levels of a-fetoprotein in maternal blood are likely to be the commonest indication in the future. (3) When high risks are expected on empirical grounds. The risk of mongolism rises with maternal age to 1 in 100 at 40-45 and 1 in 40 at 45 and over. (Your editorial is again in error in giving over 1 in 40 for births over 40; the average age of mothers over 40 is only slightly over 40.) As many pregnancies in the over-forties are either desperately wanted or equally desperately unwanted, not all are candidates for selective abortion. A serious practical problem arises when chromosomal variants of minor consequence, such as XXX, XYY, or XXY are discovered. The guidelinesgive no evidence on this. The procedure is, of course, strongly contraindicated when termination is uncon-

ditionally unacceptable. The problems are difficult and have hardly been made easier by either the enthusiasms of television or journalism, especially on Sundays, and of various armchair strategists, or by the apathy of the M.R.C. and the D.H.S.S. May I suggest that we at least attempt to use the distinct words prevention, therapy, and elimination, distinctly and, since the cause of a disorder is not relevant to its immediate technical and ethical problems, to speak of fetal disease, reserving the term genetic disease for disorders determined at

conception. Infant Development Unit, Birmingham Maternity Hospital, Birmingham B15 2TG.

Raeburn’sfigures,3 which the editorial referred to, follows: in a total of 166 amniocentesis done after the birth of a child with Down’s syndrome, 6 affected fetuses were diagnosed; in 173 mothers over forty, 8 had affected fetuses.-ED. L.

**

were as

EVALUATION OF LABORATORY TESTS

SIR,—Frotessor

of Genetic Disease. Prenatal Diagnosis Newsletter (Medical Research Council of Canada),

1974, 3,

no.

1.

Diagnosis

Holland

and

Protessor

WhItehead

(Aug. 17, p. 391) performed an admirable service in calling attention to the need for rigorous evaluation of proposed laboratory tests. I should like to take issue, however, with a suggestion they make in their discussion of reference, or normal ", values. In their example of an effective communication of reference values they advocate "

the reporting of the mean and standard deviation of the values in addition to demographic and technical information regarding the subjects and procedure. I heartily endorse the recommendation of background information on the reference population and test procedure and wish that the suggestion of more complete information had been extended Littlefield, J. W., Milunsky, A., Atkins, L. in Birth Defects (edited by A. G. Motulsky and W. Lenz); p. 221. Amsterdam, 1974. 3. Raeburn, J. A. in Modern Trends in Pædiatrics (edited by J. Apley); p. 109. London, 1974.

2.

1. Guidelines for Antenatal

J. H. EDWARDS.

*