ataxias and transmissible agents

851

ATAXIAS AND TRANSMISSIBLE AGENTS

SIR,ŁThe correspondence between kuru and scrapie hasbeen further extended by the experimental transmission of kuruto chimpanzees. Following the hypothesis that kuru may be alate sequel to contact with an environmental agent which istransmitted horizontally to women and vertically from mothersto offspring,2 3 I have examined the data of Parry for evidenceof any natural transmission of the scrapie agent in sheep.Pooled data from his paper (table 2 and twin data) show thatscrapie is significantly more common than expected amongstthe offspring of presumptive heterozygous sires and homo-

zygous dams, while it is less common than expected among theoffspring of the reciprocal crosses between presumptive homo-zygous sires and heterozygous dams (see accompanying table).

ACTUAL AND EXPECTED INCIDENCE OF SCRAPIE IN OFFSPRING OF

HETEROZYGOUS AND HOMOZYGOUS SHEEP, FROM PARRY’S DATA 4

These particular deviations were predicted from a model 6

postulating that: (a) natural passage of the scrapie agent isusually by vertical transmission from mother to offspring;(b) Homozygous sheep (ss) 4 develop scrapie only if they alsoreceive the agent from the mother; and (c) occasional instancesof horizontal transmission of the agent can occur which accountfor the reported epidemics of scrapie. The exact mechanismsof vertical transmission postulated for kuru and scrapie areobscure. Obvious possibilities are cytoplasmic inheritance, ortransmission of the agent in the ovum, via the placenta, in themilk, or merely by close contact with the mother. Results fromthe mouse-scrapie system suggest that placental transmissionof the agent can occur. s

Genetic factors undoubtedly determine susceptibility to

other familial neurological disorders which show some resem-blance to kuru and scrapie, but the following data suggest thattransmissible agents could sometimes be implicated xtiologi-cally :

1. The striking anticipation ’ 8 seen in genealogies of some of theataxias and other neuromuscular disorders, although conventionallyattributed to artefacts of ascertainment,9 may under conditions ofmore complete ascertainment, as with kuru,3 merely reflect an initialepidemic situation.

2. Positive birth-order effects have been suggested for otherneurological diseases in man,4 as well as for kuru. 5

3. The high incidence of familial ataxias in geographically isolatedgroups, as in Sweden,lO could reflect the action of genetic drift onsmall population groups initially not exposed to the hypotheticalagent.

4. A tendency for familial ataxias to be transmitted throughaffected females more commonly than through affected males hasbeen cited.’ 7

5. Schut and Book 11 noted in ataxic families that affected mem-bers with an affected mother showed evidence of more severe diseaseand a shorter course than did members born of affected male parents.

J. D. MATHEWS.Kuru Research Office, Okapa,

Eastern Highlands, New Guinea.

1. Gajdusek, D. C., Gibbs. C. J., Alpers, M. Science, N. Y. 1967, 155, 212.2. Mathews, J. D. Lancet, 1965, i, 1138.3. Mathews, J. D. ibid. April 15, 1967, p. 821.4. Parry, H. B. Heredity, 1962, 17, 75.5. Mathews, J. D. Unpublished.6. Gibbs, C. J., Gajdusek, D. C., Morris, J. A. National Institute of

Neurological Diseases and Blindness, monograph no. 2; p. 195. U.S.Public Health Service Publication, no. 1378; Washington, D.C. 1965.

7. Greenfield, J. G. The Spinocerebellar Degenerations. Oxford, 1954.8. Bell, J., Carmichael, E. A. Treasury of Human Inheritance; vol. IV,

part 3. London, 1939.9. Penrose, L. S. Ann. Eugen. 1948. 14, 125.

10. Sjögren, T. Acta psychiat. neurol. scand. 1943, suppl. 27, p. 1.11. Schut, J. W., Böök, J. A. A.M.A. Archs Neurol. Psychiatry, 1953,

70, 169.

ADULT CŒLIAC DISEASE AND NEUROPATHY

SIR,-I was interested in your leading article (March 25,p. 664). I am prompted to describe a patient attending thishospital whose main neurological disorder is optic atrophy,which I believe has not been described previously in associa-tion with adult coeliac disease. As in some of those patientsdescribed by Cooke and Smith, this patient’s predominatingsymptoms have been neurological and his diarrhoea has notbeen a problem.The patient, a 52-year-old collier, first presented to another

hospital in 1962 with a 10-year history of paraesthesiae in hishands and feet, becoming worse, and latterly associated withcarpopedal spasm. He had become tired over the previousyear. He volanteered no other symptoms, but admitted tohaving brief episodes of diarrhoea all his life, which lasted 1-2days and consisted of the passage of 6-8 loose greasy stoolsper 24 hours. Otherwise his bowels were open twice daily.He had clubbing of fingers and toes, and Trousseau’s andChvostek’s signs were positive. Serum calcium 5-2 mg. and

phosphate 3-5 mg., per 100 ml.; haemoglobin 78%, withhypochromia; serum-vitamin-B.12 262 (Jo(Jog. per 100 ml.Between 9 and 23 g. of fat were passed each day in his stools.Barium-meal follow-through showed very rapid transit withchanges consistent with malabsorption.

Adult coeliac disease was diagnosed and the patient wasdischarged from hospital on a gluten-free diet with calcium,iron, and vitamin-D supplements. His symptoms of parass-thesiae greatly improved on this regimen, and he was no longertroubled by episodes of severe diarrhoea. However, he lateradmitted that he had not adhered rigidly to the diet, and hadeaten gluten-containing bread about twice a week.

In 1964 the patient again had tingling in his hands and feet,and in addition had numbness in his hands and in his legsbelow the knees. He had weakness of finger movements, as inturning taps or using clothes-pegs, and dragged his feet onwalking. These symptoms have persisted since with minorfluctuations in severity. In addition deterioration of visionin his two eyes began in 1964 and has become progressivelyworse since.

The patient was admitted to this hospital under Dr. IdrisJones in September, 1966, because of the deterioration in hisvision. He was then having bowel actions 2-3 times a day, hisstools being pale, yellow, and sticky. He was a small man,weight 96 lb. (44 kg.) and height 5 ft. (152 cm.), with clubbingof the fingers and toes. He had bilateral optic atrophy, withstriking constriction of both visual fields, particularly thenasal halves. Visual acuity was 6/6 in the left eye, and 6/36in the right eye. He had peripheral neuropathy, with weaknessof movements involving the small muscles of the hands, glove-and-sock impairment of sensation to pinprick, and sluggishankle-jerks. Investigations showed: haemoglobin 96%; meancorpuscular hxmoglobin concentration 34%; mean cor-

puscular volume 100 c.pL; serum calcium 8-6, magnesium 2-1,and phosphate 5, mg. per 100 ml.; serum albumin 31 andglobulin 3-2, g. per 100 ml.; serum-vitamin-B.12 126 ppg. per100 ml.; serum-iron 73 (Jog. per 100 ml.; and total iron-bindingcapacity 315 (Jog. per 100 ml. Xylose-tolerance test showedexcretion of 2-1 g. in the 5-hour period following an oral doseof 25 g.; average daily fsecal-fat excretion was 11 g.; barium-meal follow-through showed rapid transit with dilatation ofthe jejunal loops and clumping of barium; and jejunal-biopsyshowed short thick villi with inflammatory mucosal changes.

This patient therefore presented with the features of adultcoeliac disease with malabsorption of fat, xylose, calcium,magnesium, and folate. At present he is rigidly adhering to astrict gluten-free diet, with hydroxycobalamin, folate, calcium,vitamin-D, and iron supplements. In the past 6 months therehas been further visual deterioration. His mild peripheralneuropathy remains unchanged.

I do not feel this patient’s optic atrophy can be explainedin terms of any single vitamin deficiency. I agree with you

1. Cooke, W. T., Smith, W. T. Brain, 1966, 89, 683.