HEREDITARY COPROPORPHYRIA

263 TABLE VI-VARIANCE FOR FACTORS AFFECTING HEMOGLOBIN CENTRATION IN MEN OVER 65

CON-

We should like to express our sincere thanks to Dr. Sybil Birtwistle, Dr. Peter Eckstein, Dr. David Emerson, Dr. Shirley Emerson, Dr. Bernard Reiss, and Dr. Neville Silverston for their interest and cooperation. We are grateful to Mr. R. G. Carpenter, of the department of human ecology, for advice in the preparation of the survey. This survey was made possible by a grant to one of us (A. M. M.) from the Clinical Research Funds of the Board of Governors of the United Cambridge Hospitals. We are indebted to the mathematical laboratory, University of Cambridge, for the use of the computer. Requests for reprints should be sent to D. G. C., Addenbrooke’s

Hospital, Cambridge. REFERENCES

Regression coefficients: bA=l’768, bB=l’048. TABLE VII-VARIANCE FOR CONFINEMENT TO HOUSE IN RELATION TO HEMOGLOBIN CONCENTRATION IN WOMEN OVER

65

Campbell, H., Greene, W. J. W., Keyser, J. W., Waters, W. E., Weddell, J. M., Withey, J. L. (1968) Br. J. prev. soc. Med. 22, 41. Dacie, J. V., Lewis, M. (1963) Practical Hæmatology. London. Freiman, H. B., Tauber, S. A., Tulsky, E. G. (1963) Geriatrics, 18, 716. Hawkins, W. W., Speck, E., Leonard, V. (1954) Blood, 9, 999. Hobson, W., Blackburn, F. K. (1953) Br. med. J. i, 647. Kilpatrick, G. S., Hardisty, R. M. (1961) ibid. i, 778. Mavor, W. O. (1964) Unpublished. Morgan, R. (1965) M.D. thesis, University of Cambridge. Pincherle, G., Shanks, J. (1967) Br. J. prev. soc. Med. 21, 40. Semmence, A. M. (1959) Br. med. J. ii, 1153. Walsh, R. J., Arnold, B. J., Lancaster, H. O., Coote, M. A., Cotter, H. (1953) Spec. Rep. Ser. natn. Hlth med. Res. Coun., Canberra, no. 5. Wintrobe, M. M. (1961) Clinical Hæmatology; p. 111. Boston, Mass.

HEREDITARY COPROPORPHYRIA

J. J. CONNON M.B.

Belf., M.R.C.P.

RESEARCH FELLOW

Regression

meat,

fish,

dietary

believe in "

eggs daily, and 70% had during the week. Answers

fresh fruit the questions habits often included comments such as, "I or

or tomatoes

on

coefficient: b = -0-787.

feeding sensibly ", " you

eaten

V. TURKINGTON M.Sc. Belf., A.R.I.C. BIOCHEMIST

From the Department of Medicine, Queen’s University of Belfast, and Biochemistry Department, Royal Victoria Hospital, Belfast

to

must

keep yourself

patient with hereditary coproporphyria Summa ummary A had recurrent attacks of hepatocellular

look after ourselves ". These sponjaundice and photosensitivity. In an investigation of firm but a counted, impression porphyrin metabolism in the patient’s family, her father replies and one sister were found to have latent coproporphyria. was gained that these elderly people ate sensibly in order to remain fit. In considering medical factors, perhaps the Introduction most unexpected finding was the increased mean hmmoand Dobriner Watson et al. (1949) described (1936) globin level in men with chronic indigestion. We have who excreted no objective evidence to explain this, but these patients large amounts of coproporphyrin patients and in the urine faeces, without any other abnormality of were very conscious of the effects of diet on their metabolism. The disorder was termed symptoms and seemed to be more particular about the porphyrin " composition and frequency of their meals. Among the " hereditary coproporphyria by Berger and Goldberg men with chronic urinary symptoms, 1 patient with (1955) when they reported four cases in a Swiss familya 10-year-old boy, his parents, who were first cousins, been but carcinoma has noted, excluding prostatic already him from the group does not bring the mean haemoglobin and his paternal aunt. Thirty cases have now been to within the normal range. The cause of chronic urinary reported (Goldberg et al. 1967), half of whom were but in the was not this symptom-free, the remainder having symptoms like symptoms investigated survey, association of these symptoms with a significant incidence those of acute intermittent porphyria. Skin photosensiof anxmia is of relevance to clinicians. tivity has been described in only one case of hereditary the in 45 housecoproporphyria (Langhof et al. 1965). The patient Morgan (1965), estimating hxmoglobin described here presented with photosensitivity and bound patients over 65, found that 41 % were anxmic, and all were iron-deficient. This was twice the proportion hepatocellular jaundice. Evidence of latent porphyria was found in her father and sister. of anxmic subjects of the same age-group in his random sample. Together with the present findings, this suggests Case-report that housebound people are especially liable to develop A 19-year-old female clerk, first seen in August, 1964, had ansemia and perhaps should be regarded as a group at risk. had facial blisters for a week and generalised itching for 2 However, there is no clear association between the reason months. Staphylococcus aureus was cultured from the weeping, for being confined to the home and the prevalence of crusted blisters. It was specifically noted that jaundice was absent. The patient improved after antibiotic treatment. In anxmia. The results of our survey suggest that fit elderly 1964, the pruritus returned, and she became people are very conscious of the value of a normal diet December, nauseated and then jaundiced. Liver-function tests on Jan. and that although the haemoglobin levels in both men and showed hepatocellular dysfunction (bilirubin 4-8 1965, 27, women were slightly below the average for healthy adults mg. per 100 fit, serum-glutamic-oxaloacetic-transaminase of all ages (Wintrobe 1961), they are well within the (s.G.o.T.) 160 units per ml., serum-glutamic-pyruvic-transnormal range. Any fall in haemoglobin in the elderly must aminase (S.G.P.T.) 470 units per ml. A qualitative test for be attributed to an abnormality of health or environment urinary porphyrins was strongly positive. There was a further remission, but in May, 1966, the same symptom and not to age alone.

fit ",

or

taneous

we must

were not

264 PORPHYRIN EXCRETION IN THE PATIENT AND HER FAMILY

with similar liver-function abnormalities. 1-month pregnant at this time. Her jaundice gradually resolved, and 5 months later her serum-bilirubin was normal, but S.G.O.T. was 64 units per ml. and S.G.P.T. was 61 units per ml. The pregnancy was uneventful. In January, 1968, quantitative measurement of her urinary and faecal porphyrins showed high levels of coproporphyrin excretion.

complex returned, She

was

F’:11I1/1y Hisrory The porphyrin excretion of the patient’s father, mother, two sisters, and one brother was investigated (see table). Samples could not be obtained from other sibs. Urinary and fascal porphyrins were measured by the method of Rimington (1961), and porphobilinogen and urinary 8-aminolxvulic acid by the method of Mauzerall and Granick (1956). Her father and one sister excreted increased amounts of coproporphyrin and protoporphyrin in the fxces. Her brother had

an

increased fxcal excretion of

protoporphyrin

only. None of these people had symptoms which could be ascnbed

to

coproporphyria.

Discussion of early reports coproporphyria emphasised its nature benign (Dobriner 1936, Watson et al. 1949, and Berger Goldberg 1955), in contrast to the abdominal, and cutaneous symptoms of acute intermittent nervous, and variegate porphyria. It is now clear, however, that hereditary coproporphyria may present with acute episodes of abdominal pain, constipation, and psychiatric disturbance (Barnes and Whittaker 1965, Smart et al. 1965, Goldberg et al. 1967). In some cases barbiturates, anticonvulsants, and biological-oxidation inhibitors have precipitated the acute symptoms (Cowger and Labbe 1965, Smart et al. 1965), but in others these drugs have had no adverse effects (Barnes and Whittaker 1965, Goldberg et al. 1967). Our patient had an exacerbation of photosensitivity and felt dazed and lethargic after taking a hypnotic on one occasion. Her father has taken barbiturates several times without ill-effect. Only one other case of hereditary coproporphyria with photosensitivity has been described (Langhof et al. 1965). That patient had evidence of hepatic disease, manifested by 33°,, retention of bromsulphthalein, and fine cirrhosis was found at necropsy. She was not

The

jaundiced. Two of the three episodes of jaundice in our patient associated with photosensitivity. The first bout of jaundice occurred in mid-winter, at which time photosensitivity was unlikely. Jaundice is a rare manifestation of porphyria, except in the hepatic cutaneous type associated with alcoholism. The nature of the liver disease in the propositus is uncertain. It may have been caused by concurrent infection by hepatitis virus which unmasked latent coproporphyria. On the other hand, the first attack of photosensitivity occurred in the absence of overt liver disease, and it is possible that the metabolic defect in coproporphyria may affect hepatocellular function. were

Five of ten patients described by Goldberg et al. (1967) had psychiatric symptoms, and it is noteworthy that four of the father’s sibs in the present investigation also have mental disorders. One is an alcoholic, one drinks excessively but has not yet required treatment, one has an anxiety neurosis, and the fourth has had psychotic episodes. The subject with the anxiety neurosis has two sons, one of whom has cerebral palsy and the other is schizophrenic. The porphyrin metabolism of these patients has not yet been investigated, but in view of the proposed autosomal dominant pattern of inheritance it seems likely that some of them have coproporphyria. We hope to measure the porphyrin excretion of these patients and their children (a total of about 50 subjects) to establish the inheritance pattern of the disorder. Thanks are due to Prof. G. M. Bull, Prof. J. Vallance-Owen, and Dr. J. A. Weaver for permission to study the patient, and to Mr. D. W. Neill for laboratory facilities. I wish to acknowledge my thanks for a Royal Victoria Hospital Research Fellowship, during the tenure of which this work was carried out.

Requests for reprints should be sent to J. J. C. at the Royal VicHospital, Grosvenor Road, Belfast, BT12 6BA.

toria

REFERENCES

Barnes, H. D., Whittaker, N. (1965) Br. med. J. ii, 1102. Berger, H., Goldberg, A. (1955) ibid. ii, 85. Cowger, M. L., Labbe, R. F. (1965) Lancet, i, 88. Dobriner, K. (1936) Proc. Soc. exp. Biol. Med. 35, 175. Goldberg, A., Rimington, C., Lochhead, A. C. (1967) Lancet, i, 632. Langhof, H., Franken, E., Kluge, K. (1965) Hautartzt, 3, 101. Mauzerall, D., Granick, S. (1956) J. biol. Chem. 219, 435. Rimington, C. (1961) Association of Clinical Pathologists broadsheet no. 36. Smart, G. A., Herbert, F. K., Whittaker, N., Barnes, H. D. (1965) Lancet, i, 318. Watson, C. J., Schwartz, S., Schulze, W., Jacobson, L. O., Zagaria, R. (1949) J. clin. Invest. 28, 465.

Preliminary Communication HYPERINSULINISM AND CARBOHYDRATEINDUCED HYPERLIPOPROTEINÆMIA

patient is described with carbohydrateA Summary inducible hyperlipoprotemæmia, raised

serum-free-fatty-acid, and glycerol levels associated with hyperinsulinism. A carbohydrate-restricted diet led to clinical remission, a fall in insulin levels, clearing of the lipæmic plasma, and a return to normal of the free-fattyacid and glycerol levels. INTRODUCTION

ENDOGENOUS (type iv) hyperlipoproteinxmia, as defined by Fredrickson et al.1, is induced by carbohydrate and accompanied by glucose intolerance. There is a striking increase in the pre-&bgr;-lipoprotein fraction with a rise in glycerides and, commonly, in cholesterol also. We have 1.

Fredrickson, 276, 273.

D.

S., Levy, R. I., Lees, R. S. New Engl. J. Med. 1967,