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HYPERCAROTENÆMIA IN GHANAIANS
1151 of the complexes, suggests that similar processes may be
operative in atherogenesis.
evidence is required Although for a definitive conclusion, indirect support pointing in this direction is provided by the investigations of Morrison et al.,8 who were able to counteract the development of experimental atherosclerotic lesions by administering chondroitin sulphate A. It seems that the locally increased permeability of the inner surfaces of the arteries, combined with a decreased permeability of the adjacent areas, creates a situation particularly favourable for the development of the plaques. The Gaubius Institute of
Leyden University, The Netherlands.
more
F. B. KLYNSTRA E. BOELSMA-VANHOUTE C. J. F. BÖTTCHER.
HYPERCAROTENÆMIA IN GHANAIANS
SIR,-High values of serum-carotene have been found in various parts of Ghana.4 I report here, however, an unusually high value of serum-carotene in a premature infant. A blood-sample was taken from a premature baby girl (birth-weight 1640 g.) who was admitted to the Korle Bu Hospital, Accra, on the fourth day of life with jaundice. The serum, which was very pigmented, was analysed for carotene,5 and the level found to be 8700 {.lg. per 100 ml.-fifteen to twenty times the average carotene value reported in adult Ghanaians.4 The pigment extracted from the serum was identified as carotene by spectrochromatography. Further analyses could not be made because the baby died. The question is therefore raised whether high serum-carotene levels are without any consequences. I wish samnle.
to
thank Dr. Christine Gilbert for
National Institute of Health, and Medical Research, P.O. Box 2848, Accra, Ghana.
providing the blood-
J. MAUD DAGADU.
PYRIDOXINE TREATMENT IN HOMOCYSTINURIA SIR,-Dr. Barber and Dr. Spaeth 6 have reported the effects of large doses of pyridoxine in restoring to normal the raised plasma-methionine levels and the urinary excretion of homocystine in three patients with homocystinuria. Professor Hooft and his colleagues ’achieved improvement in these biochemical criteria in two patients by the same treatment. We have now treated two patients with homocystinuria with large doses of pyridoxine for a period of 5 months.
Case 1.-A boy of 4 years, previously reported as case 7had been maintained on a low-protein diet before treatment. The pretreatment plasma-methionine level was 0.273 moles per ml. Treatment with pyridoxine 250 and 500 mg. daily by mouth for one month on each dose produced no change in the methionine levels. Returning him to an ad-lib diet with 250 mg. pyridoxine daily reduced his methionine level to 0-096 ILmoles per ml., and the further addition of a dietary supplement of cystine, 150 mg. per kg. per day, effected a further lowering to 0-071 timoles per ml. No significant change in the plasma-homocystine level was noted, but cystine and the mixed disulphide of cysteine-homocysteine appeared in the plasma. The cyanide-nitroprusside reaction remained positive in the urine. Case 2.-A 9-year-old girl, case 5 of our previous report,8 had also been maintained on protein restriction before pyridoxine treatment. The pretreatment plasma-methionine level was 0-69 moles per ml. Pyridoxine in similar dosage produced no effect nor did return to a full diet. Treatment was 3. 4.
5. 6. 7. 8.
Morrison, L., Murata, K., Quilligan, J. J., Schjeide, O. A., Freeman, L. Circulation Res. 1966, 19, 358. Dagadu, J. M., Gillman, J. Lancet, 1963, i, 531. Dagadu, J. M. Ghana med. J. 1963, ii, 153; ibid. 1965, iv, 121. Glick, D. Methods of Biochemical Analysis; vol. IV. New York, 1957. Barber, G. W., Spaeth, G. L. Lancet, 1967, i, 337. Hooft, C., Carton, D., Samyn, W. ibid. p. 1384. Turner, G., Dey, J., Turner, B. Aust. pœdiat. J. 1967, 3, 48.
complicated by an acute psychotic illness which was accompanied by elevation of the plasma-methionine level to 0.126 moles per ml.; this returned to 0.052 moles per ml. with recovery and the addition of a cystine supplement. The plasma-homocystine level remained unaltered throughout the period but cystine and the mixed disulphide have appeared in her plasma. The observations suggest that the maintenance of
an
adequate protein intake and possibly a cystine supplement are necessary for pyridoxine to produce the presumably desirable effect of lowering the plasma-methionine level and increasing the cystine level. The psychotic episode in case 2 recalls the exacerbations of schizophrenia produced by methionine loading,9 but no exciting factor could be identified in the girl. The value of pyridoxine therapy in homocystinuria seems to lie in its ability to control or ameliorate the biochemical abnormalities without recourse to dietary restriction. The variability of response from patient to patient noted by Professor Hooft and his colleagues seems to occur within a sibship and may not represent different genetic variants of the disease. We are indebted to Dr. H. Goodman (Andrews Laboratories) for making pyridoxine hydrochloride available. Oliver Latham Laboratory,
Psychiatric Centre, North Ryde 2113, New South Wales.
BRIAN TURNER.
THE " AT-RISK " INFANT SIR,-We should like to comment on some of the more important points raised in the correspondence about our article
(Sept. 30, p. 711). Although our article questions the value of the " at-risk register from what might be considered an academic viewpoint, our very practical interest in this subject is based on our joint experience of screening 90,000 births for congenital malformations, the neurological and developmental examination of 2000 infants under two years of age, and the audiological assessment of 3000 infants and schoolchildren. The greatest source of misunderstanding in the correspondence seems to have been the confusion of the at-risk concept with the need for early detection of handicaps. We certainly would not deny the importance of early detection-our thesis is that the at-risk register is not satisfactory for the purpose. It is clear that considerable differences of opinion exist about the value and difficulty of early developmental assessment. We had no intention of implying that developmental neurological, and audiological assessment before ten months, undertaken by experienced clinicians in well-staffed and wellequipped assessment clinics, was inefficient. Our comments should be considered in the context of our article-namely, population screening. We still feel that many of the techniques which work well in the hands of the experienced may be difficult and of limited value when applied to large numbers of children examined in situations of varying suitability by personnel of varied and sometimes limited training. Dr. Mac Keith (Oct. 21, p. 886) states that " despite what Dr. Richards and Dr. Roberts say,’suitable auditory screening tests for use in the whole infant population ’ have been in existence for years." His statement is based on the assumption that the reason why many deaf children are still reaching school age without detection is that health visitors are not carrying out the tests properly-the sensitivity, specificity, and repeatability of these tests are not questioned. In our experience, many more children with auditory defects are being missed, when screened in infancy, than are being detected. We feel that this is due to inherent weaknesses of present-day tests, and that far more attention should be paid to the need for frequency and intensity specificity and to the importance of understanding fully the complex developmental and neuro9.
Park, L. C., Baldessarini, R. J., Kety, S. S. Archs 12, 346.
gen.
Psychiat. 1965,
operative in atherogenesis.
evidence is required Although for a definitive conclusion, indirect support pointing in this direction is provided by the investigations of Morrison et al.,8 who were able to counteract the development of experimental atherosclerotic lesions by administering chondroitin sulphate A. It seems that the locally increased permeability of the inner surfaces of the arteries, combined with a decreased permeability of the adjacent areas, creates a situation particularly favourable for the development of the plaques. The Gaubius Institute of
Leyden University, The Netherlands.
more
F. B. KLYNSTRA E. BOELSMA-VANHOUTE C. J. F. BÖTTCHER.
HYPERCAROTENÆMIA IN GHANAIANS
SIR,-High values of serum-carotene have been found in various parts of Ghana.4 I report here, however, an unusually high value of serum-carotene in a premature infant. A blood-sample was taken from a premature baby girl (birth-weight 1640 g.) who was admitted to the Korle Bu Hospital, Accra, on the fourth day of life with jaundice. The serum, which was very pigmented, was analysed for carotene,5 and the level found to be 8700 {.lg. per 100 ml.-fifteen to twenty times the average carotene value reported in adult Ghanaians.4 The pigment extracted from the serum was identified as carotene by spectrochromatography. Further analyses could not be made because the baby died. The question is therefore raised whether high serum-carotene levels are without any consequences. I wish samnle.
to
thank Dr. Christine Gilbert for
National Institute of Health, and Medical Research, P.O. Box 2848, Accra, Ghana.
providing the blood-
J. MAUD DAGADU.
PYRIDOXINE TREATMENT IN HOMOCYSTINURIA SIR,-Dr. Barber and Dr. Spaeth 6 have reported the effects of large doses of pyridoxine in restoring to normal the raised plasma-methionine levels and the urinary excretion of homocystine in three patients with homocystinuria. Professor Hooft and his colleagues ’achieved improvement in these biochemical criteria in two patients by the same treatment. We have now treated two patients with homocystinuria with large doses of pyridoxine for a period of 5 months.
Case 1.-A boy of 4 years, previously reported as case 7had been maintained on a low-protein diet before treatment. The pretreatment plasma-methionine level was 0.273 moles per ml. Treatment with pyridoxine 250 and 500 mg. daily by mouth for one month on each dose produced no change in the methionine levels. Returning him to an ad-lib diet with 250 mg. pyridoxine daily reduced his methionine level to 0-096 ILmoles per ml., and the further addition of a dietary supplement of cystine, 150 mg. per kg. per day, effected a further lowering to 0-071 timoles per ml. No significant change in the plasma-homocystine level was noted, but cystine and the mixed disulphide of cysteine-homocysteine appeared in the plasma. The cyanide-nitroprusside reaction remained positive in the urine. Case 2.-A 9-year-old girl, case 5 of our previous report,8 had also been maintained on protein restriction before pyridoxine treatment. The pretreatment plasma-methionine level was 0-69 moles per ml. Pyridoxine in similar dosage produced no effect nor did return to a full diet. Treatment was 3. 4.
5. 6. 7. 8.
Morrison, L., Murata, K., Quilligan, J. J., Schjeide, O. A., Freeman, L. Circulation Res. 1966, 19, 358. Dagadu, J. M., Gillman, J. Lancet, 1963, i, 531. Dagadu, J. M. Ghana med. J. 1963, ii, 153; ibid. 1965, iv, 121. Glick, D. Methods of Biochemical Analysis; vol. IV. New York, 1957. Barber, G. W., Spaeth, G. L. Lancet, 1967, i, 337. Hooft, C., Carton, D., Samyn, W. ibid. p. 1384. Turner, G., Dey, J., Turner, B. Aust. pœdiat. J. 1967, 3, 48.
complicated by an acute psychotic illness which was accompanied by elevation of the plasma-methionine level to 0.126 moles per ml.; this returned to 0.052 moles per ml. with recovery and the addition of a cystine supplement. The plasma-homocystine level remained unaltered throughout the period but cystine and the mixed disulphide have appeared in her plasma. The observations suggest that the maintenance of
an
adequate protein intake and possibly a cystine supplement are necessary for pyridoxine to produce the presumably desirable effect of lowering the plasma-methionine level and increasing the cystine level. The psychotic episode in case 2 recalls the exacerbations of schizophrenia produced by methionine loading,9 but no exciting factor could be identified in the girl. The value of pyridoxine therapy in homocystinuria seems to lie in its ability to control or ameliorate the biochemical abnormalities without recourse to dietary restriction. The variability of response from patient to patient noted by Professor Hooft and his colleagues seems to occur within a sibship and may not represent different genetic variants of the disease. We are indebted to Dr. H. Goodman (Andrews Laboratories) for making pyridoxine hydrochloride available. Oliver Latham Laboratory,
Psychiatric Centre, North Ryde 2113, New South Wales.
BRIAN TURNER.
THE " AT-RISK " INFANT SIR,-We should like to comment on some of the more important points raised in the correspondence about our article
(Sept. 30, p. 711). Although our article questions the value of the " at-risk register from what might be considered an academic viewpoint, our very practical interest in this subject is based on our joint experience of screening 90,000 births for congenital malformations, the neurological and developmental examination of 2000 infants under two years of age, and the audiological assessment of 3000 infants and schoolchildren. The greatest source of misunderstanding in the correspondence seems to have been the confusion of the at-risk concept with the need for early detection of handicaps. We certainly would not deny the importance of early detection-our thesis is that the at-risk register is not satisfactory for the purpose. It is clear that considerable differences of opinion exist about the value and difficulty of early developmental assessment. We had no intention of implying that developmental neurological, and audiological assessment before ten months, undertaken by experienced clinicians in well-staffed and wellequipped assessment clinics, was inefficient. Our comments should be considered in the context of our article-namely, population screening. We still feel that many of the techniques which work well in the hands of the experienced may be difficult and of limited value when applied to large numbers of children examined in situations of varying suitability by personnel of varied and sometimes limited training. Dr. Mac Keith (Oct. 21, p. 886) states that " despite what Dr. Richards and Dr. Roberts say,’suitable auditory screening tests for use in the whole infant population ’ have been in existence for years." His statement is based on the assumption that the reason why many deaf children are still reaching school age without detection is that health visitors are not carrying out the tests properly-the sensitivity, specificity, and repeatability of these tests are not questioned. In our experience, many more children with auditory defects are being missed, when screened in infancy, than are being detected. We feel that this is due to inherent weaknesses of present-day tests, and that far more attention should be paid to the need for frequency and intensity specificity and to the importance of understanding fully the complex developmental and neuro9.
Park, L. C., Baldessarini, R. J., Kety, S. S. Archs 12, 346.
gen.
Psychiat. 1965,