- Email: [email protected]
LINOLEIC ACID IN MULTIPLE SCLEROSIS
1197
logical diseases,
as well as iron-deficiency anaemia 13 and sickle-cell anaemia.11-16 Raised serum-copper concentrations are also seen in other hsematological disorders, such
There was little difference in response between the induced and spontaneous groups when the patients were asked how the actual length of labour compared with what they had expected:
thalassaemia, aplastic anaemia, pernicious anaemia,17,18
as
and other carcinomas.19-21 Department of Surgery, Cleveland Metropolitan General
Hospital. Department of Dermatology, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, U.S.A.
WILLIAM H. STRAIN. When asked specifically about pain, 45 % of the induced patients reported that labour had been more painful than expected, compared with 33% of the spontaneous group. The majority of patients reported that relief from anxiety was obtained by helpful and sympathetic staff and by the presence of the husband. These patients were in favour of having a subsequent induction.
FRED S. HIRSH BENO MICHEL.
PATIENT RESPONSE TO INDUCTION OF LABOUR
SiR,—We have carried
out a
prospective
survey
on
This information shows that a high degree of patient can be obtained by careful explanation of induction of labour. Sympathetic support by delivery-suite staff and the presence of the husband are essential if anxiety and tension are to be relieved. The main disadvantages of induction can be relieved. Amniotomy and oxytocin have a very low failure rate, and the caesarean-section rate and forceps rate can be kept at an acceptable level.’
acceptability
200
determine their reaction to induction of labour. Antenatal patients, between the 34th and 36th week of pregnancy, were invited to answer a questionnaire. The patients were delivered either spontaneously or after induction. A further questionnaire was then answered, and each patient was interviewed. women to
Maternity Unit, Watford General Hospital, Watford, Herts. WD1 8HB.
80% of patients attending mothercraft classes knew about induction of labour, compared with 37-5% who did not attend classes. Only 9% of patients with a knowledge of induction actively disliked the idea, compared with 19% of patients who had not been told of induction (14% of whom were unable to answer this question, compared with 2% of the patients with a knowledge of induction). The two groups of patients answered as follows when asked to compare the expected length of labour if induced with expected length of spontaneous labour:
When
questioned similarly about expected pain,
LINOLEIC ACID IN MULTIPLE SCLEROSIS
SIR,-Several investigators have suggested that linoleic acid (L.A.) has an immunosuppressive effect in vitro 2-6 and in vivo. 6,7 Others have claimed that the suppression is specific to multiple sclerosis (M.S.).8,9 This interest in linoleic acid was provoked by previous reports 10 that patients in the acute phase of multiple sclerosis had low serum levels of L.A. and that dietary supplementation with L.A. might be beneficial.ll We are engaged in a double-blind therapeutic trial of the effect of linoleic acid in M.S. In conjunction with this trial we are measuring L.A. levels in serum during the baseline period and during the trial. We have also studied the in-vivo and in-vitro effect of L.A. on these patients’
the results
were:
72% of patients knowing about induction believed that labour would be shorter, and 44% believed labour would be more painful. When questioned after delivery there was little difference in reaction to labour between those who were induced and those who had spontaneous labour. In both groups about one-third of patients found labour easier than expected, and about onethird of patients found labour harder:
Fell, G. S., Canning, E., Husain, S. L., Scott, R. in Trace Substances in Environmental Health (edited by D. D. Hemphill); vol. v, p. 293. Columbia, Mo., 1972. 14. Olatunbosun, D. A., Isaacs-Sodeye, W. A., Adeniyi, F. A., Adadevoh, B. K. Lancet, 1975, i, 285. 15. Serjeant, G. R., Galloway, R. E., Gueri, M. C. ibid. 1970, ii, 891. 16. Karayalcin, G., Rosner, F., Kim, K. Y., Chandra, P. ibid. 1974, i, 13.
217. 17.
Cartwright, G. E., Hugnley, C. M., Ashenbrucker, H., Fay, J., Wintrobe, M. M. Blood, 1948, 3, 501. 18. Prasad, A. S., Diwany, M., Gabr, M., Sandstead, H. H., Mohktar, N., Hefny, A. E. Ann. intern. Med. 1965, 62, 87. 19. Delves, H. T., Alexander, F. W., Lay, H. Br. J. Hœmat. 1973, 24, 525. 20. 21.
Hrgovcic, M., Jessmer, C. F., Thomas, F. B., Ong, P. S., Gamble, J. F., Shullenberger, C. C. Cancer, 1973, 32, 1512. Ilicin, G. Lancet, 1971, ii, 1036.
B. V. LEWIS S. RANA ELIZABETH CROOK.
*
lymphocyte responsiveness to phytohsemagglutinin (P.H.A.). Our data show that the linoleic-acid levels in patients with stable multiple sclerosis (mean=2-81 fjunol. per ml., n=71) are not significantly different from those in normal controls (mean=3-01 mol. per ml., n=31). The linoleicacid levels of patients with other neurological diseases are lower (mean=2-48 tlmol. per ml., n=62), and patients going through an acute relapse of multiple sclerosis also have a somewhat lower level of linoleic acid (mean=2-55 jamol. per ml., n=12). This suggests that there is no specificity i4 the lower levels of linoleic acid in neurological disease, though further analysis of these data is under way. Patients taking L.A. supplements do have raised serum-L.A. levels (mean=3-80 jjunol. per ml., n=23). The P.H.A. (0-2%) responsiveness of 30 multiple-sclerosis patients, 6 normals, and 6 neurological controls was studied and linoleic acid (80 g. per ml.) depressed the blast-transformation response in virtually all patients. There did not seem to
be any difference in the reduction of response between
1. Tipton, R. H., Lewis, B. V. Br. med. J. 1974, i, 391. 2. Mertin, J., Hughes, D., Stewart-Wynne, E. Lancet, 1974, i, 1005. 3. Offner, H., Clausen, J. ibid. 1974, ii, 400. 4. Offner, H., Clausen, J. ibid. p. 1204. 5. Field, E. J., Shenton, B. K. ibid. p. 725. 6. Uldall, P. R., et al. ibid. p. 514. 7. Mertin, J. ibid. p. 717. 8. Field, E. J., Shenton, B. K., Joyce, G. Br. med. J. 1974, i, 412. 9. Jenssen, H. L., Kohler, H., Gunther, J., Meyer-Rienecker, H. Lancet, 1974, ii, 1327. 10. Baker, R. W. R., Thompson, R. H. S., Zilkha, K. J. J. Neurol. 11.
Neurosurg. Psychiat. 1966, 29, 95. H. D., et al. Br. med. J. 1973, i, 765.
Millar, J.
1198
multiple sclerosis patients and the control groups. There also was no difference in P.H.A. responsiveness between M.s. patients taking linoleic acid and patients on the control mixture (oleic acid). We have been unable to confirm that there is any specificity in the linoleic acid blood-levels in we have been able to show that L.A. is a potent inhibitor of P.H.A. responsiveness in vitro. There is no evidence that multiple-sclerosis patients taking L.A. have any reduction in P.H.A. responsiveness when compared with M.s. patients on oleic acid, even though L.A. blood-levels are raised. Multiple Sclerosis Clinic, Department of Clinical Neurological Sciences, D. W. PATY University Hospital, H. K. COUSIN University of Western Ontario, L. E. MCDONALD. London, Ontario, Canada.
M.S., but
serum-folate lower than the lower limit of normal for their laboratory. I am not including the many case-reports of the association of megaloblastic ansemias and oral contraceptives, because there is no definite proof that o.c. has been the only cause for the megaloblastic anaemia. The review of the literature leaves no doubt that oral contraceptives interfere with folate metabolism. The effect, admittedly, is mild and by itself is unlikely to cause megaloblastic anaemia in a person who has a good daily supply of folic acid. However, in a woman who does not have an optimum folate intake or has other conditions which may interfere with folate metabolism, oral contraceptives may well contribute towards the development of more severe folate deficiency and megaloblastic ansemia. Department of Hæmatology, St. Boniface General Hospital,
Winnipeg, Manitoba,
A. M.
Canada R2H 2A6.
VITAMINS AND ORAL CONTRACEPTIVE
INBORN ERROR OF CARNITINE METABOLISM (" CARNITINE DEFICIENCY")
USE
SIR,-Professor Wynn (March 8, p. 563), states that " Shojania et al.l reported lower serum-folate and red-cellfolate levels in women on oral contraceptives (o.c.) and increased urinary FIGLU excretion after histidine loading.... Several studies, however, have failed to confirm this effect of o.c.
on
serum-folate levels." He also refers
to
the review
by Chanarin,2 who concluded that " there is as yet no definite’evidence that o.c. per se induces folate deficiency". Neither Wynn, nor Chanarin, refer to any of the studies which have confirmed our findings, but Chanarin notes seven reports in which the investigators failed to show lower serum-folate in o.c. users. In a study of 176 women on o.c. and 140 controls, Shojania et al.l showed that women on o.c. had significantly lower serum and red-cell folate and higher urinary FIGLU excretion than did the controls. They showed that these abnormalities are time related. and they improve considerably within three months after discontinuation of o.c. therapy. They also have recently reported that women on o.c. excrete more folate in their urine than controls for any given level of serum or redcell folate.3Luhby et a1. reported that 25 % of 20 randomly chosen women on o.c. had increased urinary FIGLU excretion after histidine loading, 20% had low serum-folate and 15% had low red-cell folate (none of these were abnormal in their controls). Wertalik et al.5 reported -that the mean serum-folate of 20 women on o.c. was significantly lower than that of the controls and 6 out of 20 (30%) had serumfolate levels lower than the lower limit of normal in their laboratory. Alperine 6 in the study of 100 women on o.c. and 100 controls reported that women on o.c. had significantly lower serum and red-cell folate than controls. Roetz and Nevinny-Stickelin a prospective study of 60 women before and during the first twelve months of o.c. therapy showed that there was a significant fall of serum-folate in all subjects within one year of o.c. therapy. Whitehead et al.8 reported that 22 out of 115 women on o.c. (but none of the 51 controls) showed megaloblastic changes in cervical epithelium; furthermore, 7 out of 37 (19%) on o.c. had a 1. 2. 3. 4. 5. 6.
7.
Shojania, A. M., Hornady, G. J., Barnes, P. H. Am. J. Obstet. Gynec. 1971, 111, 782. Chanarin, I. Ninth Symposium on Advanced Medicine (edited by G. Walker). London, 1973. Shojania, A. M. J. Lab. clin. Med. 1975, 85, 185. Luhby, A. L., Shimizu, N., Davis, P., Cooperman, J. M. Fedn Proc. 1971, 30, 239. Wertalik, L. F., Metz, E. N., Lubuglio, A. F., Balcerzak, S. P. J. Am. med. Ass. 1972, 221, 1371. Alperine, J. B. Am. J. clin. Nutr. 1973, 26, XIX. Roetz, R., Nevinny-Stickel, J. Geburtsh. U. Frauenheik. 1973, 33, 629.
8.
Whitehead, N., Reyner, F., Lindenbaum, J. J. Am. med. Ass. 1973, 226, 1421.
SHOJANIA.
IN MAN
SIR,-Carnitine (y-trimethyl-amino- P-hydroxybutyrate) intimately concerned in the transportation of long-chain fatty acids into mitochondria1 and it is believed that its depletion causes intracellular lipid accumulation. Engel2 first reported an abnormality of carnitine metabolism with is
low tissue-carnitine levels in man in 1973, and since then six further cases have been identifieda presenting at different ages with a wide variety of symptoms.4-6 We wish to describe a further example of the condition, the first to be recognised in the U.K., although another patient recently described probably has this condition.’7 A boy, now aged 11 years, has calcification of the basal ganglia, raised cerebrospinal-fluid protein concentration, and high-tone hearing loss, in addition to the other reported features, and is thus unique. Infancy and early childhood were normal, but at the age of 5! years he complained of headaches, tired easily, and had episodes of vomiting and exertional dyspnoea. These symptoms have increased, so that now he can walk only 30 yards because of breathlessness. He has not grown since approximately 6 years. He had a generalised fit at 9 years. When examined recently, his height and weight were below the 3rd percentile, and there was generalised hypotonic weakness and wasting of moderate severity, greater proximally. Gait, tendon reflexes, plantar responses, coordination, and sensory testing were normal, but he could not run, hop, or jump. There was no muscle tenderness, myotonia, or fasciculation. He had mild sensorineural hearing loss. The liver was slightly enlarged and firm but not tender.
Haematological investigation, plasma-electrolytes, serum-lipids, plasma growth hormone, parathormone, bilirubin, calcium, phosphate, alkaline phosphatase, and urea concentrations have always been normal when examined, and so have chest radiographs, electrocardiogram, electroretinogram, visually-evoked cortical responses, and nerve conduction studies. There have been variably increased concentrations of the following: serum creatinine phosphokinase (4-2-16-7 fimol per ml. per hour at 37°C-normal values for males: 0-25-3-6 units); blood pyruvate (0-7-1-2 mg. per 100 ml.); blood lactate (20-54 mg. per 100 ml.); alanine (8 mg. per 100 ml.); A.L.T. (21-94 i.u. per 1.); (15-103 I.U. per 1.). Astrup values consistently suggested a metabolic acidosis, while respiratory function tests indicated poor respiratory reserve secondary to muscle weakness. An
plasma A.S.T.
Fredrickson, D. S., Gordon, R. S., Jr. J. clin. Invest. 1958, 37, 1504. Engel, A. G., Angelini, C. Science, 1973, 179, 899. Engel, A. G. Personal communication, 1975. Markesbery, W. R., McQuillen, M. P., Procopis, P. G., Harrison, A. R., Engel, A. G. Archs Neurol. 1974, 31, 320. 5. Karpati, G., Carpenter, S., Engel, A. G., Watters, G., Allen, J., Rothman, S., Klessen, G., Mamer, O. A. Neurology, 1975, 25, 16. 6. Vandyke, D. H., Griggs, R. C., Markesbery, W., Dimauro, S. ibid. p. 154. 7. Chanarin, I., Patel, A., Slavin, G., Wills, E. J., Andrews, T. M., Stewart, G. Br. med. J. 1975, i, 553.
1. 2. 3. 4.
logical diseases,
as well as iron-deficiency anaemia 13 and sickle-cell anaemia.11-16 Raised serum-copper concentrations are also seen in other hsematological disorders, such
There was little difference in response between the induced and spontaneous groups when the patients were asked how the actual length of labour compared with what they had expected:
thalassaemia, aplastic anaemia, pernicious anaemia,17,18
as
and other carcinomas.19-21 Department of Surgery, Cleveland Metropolitan General
Hospital. Department of Dermatology, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, U.S.A.
WILLIAM H. STRAIN. When asked specifically about pain, 45 % of the induced patients reported that labour had been more painful than expected, compared with 33% of the spontaneous group. The majority of patients reported that relief from anxiety was obtained by helpful and sympathetic staff and by the presence of the husband. These patients were in favour of having a subsequent induction.
FRED S. HIRSH BENO MICHEL.
PATIENT RESPONSE TO INDUCTION OF LABOUR
SiR,—We have carried
out a
prospective
survey
on
This information shows that a high degree of patient can be obtained by careful explanation of induction of labour. Sympathetic support by delivery-suite staff and the presence of the husband are essential if anxiety and tension are to be relieved. The main disadvantages of induction can be relieved. Amniotomy and oxytocin have a very low failure rate, and the caesarean-section rate and forceps rate can be kept at an acceptable level.’
acceptability
200
determine their reaction to induction of labour. Antenatal patients, between the 34th and 36th week of pregnancy, were invited to answer a questionnaire. The patients were delivered either spontaneously or after induction. A further questionnaire was then answered, and each patient was interviewed. women to
Maternity Unit, Watford General Hospital, Watford, Herts. WD1 8HB.
80% of patients attending mothercraft classes knew about induction of labour, compared with 37-5% who did not attend classes. Only 9% of patients with a knowledge of induction actively disliked the idea, compared with 19% of patients who had not been told of induction (14% of whom were unable to answer this question, compared with 2% of the patients with a knowledge of induction). The two groups of patients answered as follows when asked to compare the expected length of labour if induced with expected length of spontaneous labour:
When
questioned similarly about expected pain,
LINOLEIC ACID IN MULTIPLE SCLEROSIS
SIR,-Several investigators have suggested that linoleic acid (L.A.) has an immunosuppressive effect in vitro 2-6 and in vivo. 6,7 Others have claimed that the suppression is specific to multiple sclerosis (M.S.).8,9 This interest in linoleic acid was provoked by previous reports 10 that patients in the acute phase of multiple sclerosis had low serum levels of L.A. and that dietary supplementation with L.A. might be beneficial.ll We are engaged in a double-blind therapeutic trial of the effect of linoleic acid in M.S. In conjunction with this trial we are measuring L.A. levels in serum during the baseline period and during the trial. We have also studied the in-vivo and in-vitro effect of L.A. on these patients’
the results
were:
72% of patients knowing about induction believed that labour would be shorter, and 44% believed labour would be more painful. When questioned after delivery there was little difference in reaction to labour between those who were induced and those who had spontaneous labour. In both groups about one-third of patients found labour easier than expected, and about onethird of patients found labour harder:
Fell, G. S., Canning, E., Husain, S. L., Scott, R. in Trace Substances in Environmental Health (edited by D. D. Hemphill); vol. v, p. 293. Columbia, Mo., 1972. 14. Olatunbosun, D. A., Isaacs-Sodeye, W. A., Adeniyi, F. A., Adadevoh, B. K. Lancet, 1975, i, 285. 15. Serjeant, G. R., Galloway, R. E., Gueri, M. C. ibid. 1970, ii, 891. 16. Karayalcin, G., Rosner, F., Kim, K. Y., Chandra, P. ibid. 1974, i, 13.
217. 17.
Cartwright, G. E., Hugnley, C. M., Ashenbrucker, H., Fay, J., Wintrobe, M. M. Blood, 1948, 3, 501. 18. Prasad, A. S., Diwany, M., Gabr, M., Sandstead, H. H., Mohktar, N., Hefny, A. E. Ann. intern. Med. 1965, 62, 87. 19. Delves, H. T., Alexander, F. W., Lay, H. Br. J. Hœmat. 1973, 24, 525. 20. 21.
Hrgovcic, M., Jessmer, C. F., Thomas, F. B., Ong, P. S., Gamble, J. F., Shullenberger, C. C. Cancer, 1973, 32, 1512. Ilicin, G. Lancet, 1971, ii, 1036.
B. V. LEWIS S. RANA ELIZABETH CROOK.
*
lymphocyte responsiveness to phytohsemagglutinin (P.H.A.). Our data show that the linoleic-acid levels in patients with stable multiple sclerosis (mean=2-81 fjunol. per ml., n=71) are not significantly different from those in normal controls (mean=3-01 mol. per ml., n=31). The linoleicacid levels of patients with other neurological diseases are lower (mean=2-48 tlmol. per ml., n=62), and patients going through an acute relapse of multiple sclerosis also have a somewhat lower level of linoleic acid (mean=2-55 jamol. per ml., n=12). This suggests that there is no specificity i4 the lower levels of linoleic acid in neurological disease, though further analysis of these data is under way. Patients taking L.A. supplements do have raised serum-L.A. levels (mean=3-80 jjunol. per ml., n=23). The P.H.A. (0-2%) responsiveness of 30 multiple-sclerosis patients, 6 normals, and 6 neurological controls was studied and linoleic acid (80 g. per ml.) depressed the blast-transformation response in virtually all patients. There did not seem to
be any difference in the reduction of response between
1. Tipton, R. H., Lewis, B. V. Br. med. J. 1974, i, 391. 2. Mertin, J., Hughes, D., Stewart-Wynne, E. Lancet, 1974, i, 1005. 3. Offner, H., Clausen, J. ibid. 1974, ii, 400. 4. Offner, H., Clausen, J. ibid. p. 1204. 5. Field, E. J., Shenton, B. K. ibid. p. 725. 6. Uldall, P. R., et al. ibid. p. 514. 7. Mertin, J. ibid. p. 717. 8. Field, E. J., Shenton, B. K., Joyce, G. Br. med. J. 1974, i, 412. 9. Jenssen, H. L., Kohler, H., Gunther, J., Meyer-Rienecker, H. Lancet, 1974, ii, 1327. 10. Baker, R. W. R., Thompson, R. H. S., Zilkha, K. J. J. Neurol. 11.
Neurosurg. Psychiat. 1966, 29, 95. H. D., et al. Br. med. J. 1973, i, 765.
Millar, J.
1198
multiple sclerosis patients and the control groups. There also was no difference in P.H.A. responsiveness between M.s. patients taking linoleic acid and patients on the control mixture (oleic acid). We have been unable to confirm that there is any specificity in the linoleic acid blood-levels in we have been able to show that L.A. is a potent inhibitor of P.H.A. responsiveness in vitro. There is no evidence that multiple-sclerosis patients taking L.A. have any reduction in P.H.A. responsiveness when compared with M.s. patients on oleic acid, even though L.A. blood-levels are raised. Multiple Sclerosis Clinic, Department of Clinical Neurological Sciences, D. W. PATY University Hospital, H. K. COUSIN University of Western Ontario, L. E. MCDONALD. London, Ontario, Canada.
M.S., but
serum-folate lower than the lower limit of normal for their laboratory. I am not including the many case-reports of the association of megaloblastic ansemias and oral contraceptives, because there is no definite proof that o.c. has been the only cause for the megaloblastic anaemia. The review of the literature leaves no doubt that oral contraceptives interfere with folate metabolism. The effect, admittedly, is mild and by itself is unlikely to cause megaloblastic anaemia in a person who has a good daily supply of folic acid. However, in a woman who does not have an optimum folate intake or has other conditions which may interfere with folate metabolism, oral contraceptives may well contribute towards the development of more severe folate deficiency and megaloblastic ansemia. Department of Hæmatology, St. Boniface General Hospital,
Winnipeg, Manitoba,
A. M.
Canada R2H 2A6.
VITAMINS AND ORAL CONTRACEPTIVE
INBORN ERROR OF CARNITINE METABOLISM (" CARNITINE DEFICIENCY")
USE
SIR,-Professor Wynn (March 8, p. 563), states that " Shojania et al.l reported lower serum-folate and red-cellfolate levels in women on oral contraceptives (o.c.) and increased urinary FIGLU excretion after histidine loading.... Several studies, however, have failed to confirm this effect of o.c.
on
serum-folate levels." He also refers
to
the review
by Chanarin,2 who concluded that " there is as yet no definite’evidence that o.c. per se induces folate deficiency". Neither Wynn, nor Chanarin, refer to any of the studies which have confirmed our findings, but Chanarin notes seven reports in which the investigators failed to show lower serum-folate in o.c. users. In a study of 176 women on o.c. and 140 controls, Shojania et al.l showed that women on o.c. had significantly lower serum and red-cell folate and higher urinary FIGLU excretion than did the controls. They showed that these abnormalities are time related. and they improve considerably within three months after discontinuation of o.c. therapy. They also have recently reported that women on o.c. excrete more folate in their urine than controls for any given level of serum or redcell folate.3Luhby et a1. reported that 25 % of 20 randomly chosen women on o.c. had increased urinary FIGLU excretion after histidine loading, 20% had low serum-folate and 15% had low red-cell folate (none of these were abnormal in their controls). Wertalik et al.5 reported -that the mean serum-folate of 20 women on o.c. was significantly lower than that of the controls and 6 out of 20 (30%) had serumfolate levels lower than the lower limit of normal in their laboratory. Alperine 6 in the study of 100 women on o.c. and 100 controls reported that women on o.c. had significantly lower serum and red-cell folate than controls. Roetz and Nevinny-Stickelin a prospective study of 60 women before and during the first twelve months of o.c. therapy showed that there was a significant fall of serum-folate in all subjects within one year of o.c. therapy. Whitehead et al.8 reported that 22 out of 115 women on o.c. (but none of the 51 controls) showed megaloblastic changes in cervical epithelium; furthermore, 7 out of 37 (19%) on o.c. had a 1. 2. 3. 4. 5. 6.
7.
Shojania, A. M., Hornady, G. J., Barnes, P. H. Am. J. Obstet. Gynec. 1971, 111, 782. Chanarin, I. Ninth Symposium on Advanced Medicine (edited by G. Walker). London, 1973. Shojania, A. M. J. Lab. clin. Med. 1975, 85, 185. Luhby, A. L., Shimizu, N., Davis, P., Cooperman, J. M. Fedn Proc. 1971, 30, 239. Wertalik, L. F., Metz, E. N., Lubuglio, A. F., Balcerzak, S. P. J. Am. med. Ass. 1972, 221, 1371. Alperine, J. B. Am. J. clin. Nutr. 1973, 26, XIX. Roetz, R., Nevinny-Stickel, J. Geburtsh. U. Frauenheik. 1973, 33, 629.
8.
Whitehead, N., Reyner, F., Lindenbaum, J. J. Am. med. Ass. 1973, 226, 1421.
SHOJANIA.
IN MAN
SIR,-Carnitine (y-trimethyl-amino- P-hydroxybutyrate) intimately concerned in the transportation of long-chain fatty acids into mitochondria1 and it is believed that its depletion causes intracellular lipid accumulation. Engel2 first reported an abnormality of carnitine metabolism with is
low tissue-carnitine levels in man in 1973, and since then six further cases have been identifieda presenting at different ages with a wide variety of symptoms.4-6 We wish to describe a further example of the condition, the first to be recognised in the U.K., although another patient recently described probably has this condition.’7 A boy, now aged 11 years, has calcification of the basal ganglia, raised cerebrospinal-fluid protein concentration, and high-tone hearing loss, in addition to the other reported features, and is thus unique. Infancy and early childhood were normal, but at the age of 5! years he complained of headaches, tired easily, and had episodes of vomiting and exertional dyspnoea. These symptoms have increased, so that now he can walk only 30 yards because of breathlessness. He has not grown since approximately 6 years. He had a generalised fit at 9 years. When examined recently, his height and weight were below the 3rd percentile, and there was generalised hypotonic weakness and wasting of moderate severity, greater proximally. Gait, tendon reflexes, plantar responses, coordination, and sensory testing were normal, but he could not run, hop, or jump. There was no muscle tenderness, myotonia, or fasciculation. He had mild sensorineural hearing loss. The liver was slightly enlarged and firm but not tender.
Haematological investigation, plasma-electrolytes, serum-lipids, plasma growth hormone, parathormone, bilirubin, calcium, phosphate, alkaline phosphatase, and urea concentrations have always been normal when examined, and so have chest radiographs, electrocardiogram, electroretinogram, visually-evoked cortical responses, and nerve conduction studies. There have been variably increased concentrations of the following: serum creatinine phosphokinase (4-2-16-7 fimol per ml. per hour at 37°C-normal values for males: 0-25-3-6 units); blood pyruvate (0-7-1-2 mg. per 100 ml.); blood lactate (20-54 mg. per 100 ml.); alanine (8 mg. per 100 ml.); A.L.T. (21-94 i.u. per 1.); (15-103 I.U. per 1.). Astrup values consistently suggested a metabolic acidosis, while respiratory function tests indicated poor respiratory reserve secondary to muscle weakness. An
plasma A.S.T.
Fredrickson, D. S., Gordon, R. S., Jr. J. clin. Invest. 1958, 37, 1504. Engel, A. G., Angelini, C. Science, 1973, 179, 899. Engel, A. G. Personal communication, 1975. Markesbery, W. R., McQuillen, M. P., Procopis, P. G., Harrison, A. R., Engel, A. G. Archs Neurol. 1974, 31, 320. 5. Karpati, G., Carpenter, S., Engel, A. G., Watters, G., Allen, J., Rothman, S., Klessen, G., Mamer, O. A. Neurology, 1975, 25, 16. 6. Vandyke, D. H., Griggs, R. C., Markesbery, W., Dimauro, S. ibid. p. 154. 7. Chanarin, I., Patel, A., Slavin, G., Wills, E. J., Andrews, T. M., Stewart, G. Br. med. J. 1975, i, 553.
1. 2. 3. 4.