Download A1984SZ47200001

I
This Week’s
Citation Classic_________
W.
1’Carson N A I &
Nelll I)
Metabolic abnormalities detected in a survey of
mentally backward individuals in Northern Ireland.
Arch. Dis. Child. 37:505-13, 1962.
[Royal Belfast Hosp. for Sick Children, and Royal Victoria Hosp., Belfast, Northern Ireland]
During screening of mentally retarded persons in
Northern Ireland for metabolic disorders using
simple qualitative tests and two-way paper chromatography, two sisters were discovered to be excreting homocystine, a previously unrecognised
metabolic error. [The ScienceCitation Index (SC!®)
and the Social Sciences Citation Index® (SSC!®) indicate that this paper has been cited in over 195
publications since 1962.]
cific cystinuria without the presence of the
basic amino acids lysine, orithine, and arginine (all three were absent in these children),
and as I did not possess an amino acid analyser, the specimens were sent to Dent at
University College, London. In the meantime, the children were given a cystine load.
On examination of the postload urines using
large size chromatography paper and oxidising with hydrogen peroxide, two spots were
evident, one of which co-chromatographed
with cysteic acid. Dent, while first confirming our finding of cysteic acid, telegraphed
excitedly a few days later that what we had
Nina A.J. Carson
was homocysteic and not cysteic acid.
Department of Biochemistry
“This experience highlights the fact that
Royal Victoria Hospital
no one person is responsible forany new disBelfast BT12 6BA
covery. The children were referred to me by
Northern Ireland
Claude Field, paediatrician, because he Suspected the presence of an inherited meta.
June 28, 1984 bolic disorde!. My colleague and mentor
D.W. Neill, senior biochemist, encouraged
“In the 1950s, while working in a
me to pursue the investigation, and Dent
children’s hospital laboratory, I became in- and his co-workers with their expertise in
terested in developing paper chromato- amino acids were responsible for the ungraphic techniques to screen patients with
doubted identification of homocystine. Othsuspected amino acid disorders. In 1959, I
er patients were discovered in Northern Irewas given a research grant to extend this land and a typical clinical picture emerged.
work and screen the mentally retarded pop“In 1964, Mudd et al.~ reported that
ulation of Northern Ireland for metabolic er- homocystinuria was due to inactivity of cysrors. During this research, two sisters were
tathionine synthase (CS), an enzyme on the
discovered who appeared to be excreting trans-sulphuration pathway which converts
cystine in their urine. I had the opportunity
homocystine to cystathionine. Since then,
to examine the children and was impressed three genetically determined enzyme deby the similarity and unusual nature of their fects are now known in the remethylation
symptoms, i.e., mental retardation, fits, ec- pathway from homocystine to methamine.
topia lentis, and skeletal abnormalities (they (For a review of homocystinurias, see referboth later died as a result of thrombotic epi- ence 2.)
“Treatment initially was by giving a 3low
sodes).
“Chromatographic examination of urine methionine diet, then Barber and Spaeth in
1967
reported three patierits on a normal
specimens which had shown a normal amino
acid pattern when fresh, after two weeks’ diet who responded biochemically to pharstorage, revealed large spots in the cysteic macological doses of B~,thus establishing
acid position. The urine was also found to the original form of homocystinuria as an
give a positive nitroprussidelcyanide test, early example of a vitamin dependent insuggesting the presence of a sulphur-con- born error. About 40 percent of our patients
taining amino acid. It is known that the phe- are B~responsive. The reason for this often
nol solvent which we used is detrimental to quoted reference is therefore because we
thiol groups but not to the oxidised product. were the first group to discover CS homocysThis would explain the presence of the nor- tinuria. Later 4in 1962, Gerritsen, Vaughn,
mal amino acid pattern on the fresh speci- and Waisman described the first North
men of urine. As it is unusual to find a spe- American patient.”
1. Mudd S H, Flnkelateln I D, Iryever,® F L laster L. Romocyatinuna: an enzymatic defect.
Sciencg 143:1443-5. 1964. (Cited 215 times.)
2. Canon N A I. Homocystinuria—clinical and biochemical heterogeneity. (Cockburn F & Oitzelmann R, eds.)
Inborn error, of meazbo/i.rm is human,. New York: Li~s,1982. p. 53-67.
3. Barber G W & Spaetii 6 L. Pyridosine therapy in homocystinuria. LanceS 1:337, 1967. (Cited 85 times.)
4. Gerettagn T, Vaughn I 6 & Walanian N A. The identification of homocystine is the urine.
Biochem. Biophy.,. Re,. Commun. 9:493-6. 1962. (Cited 125 times.)
i2
Ce
©i9B4byIS(® CURRENT CONTENTS®
________