A study of the genetics of galactosaemia

Abstract

SummaryGalactose‐1‐phosphate uridyltransferase has been determined, by a manometric method, in the lysed erythrocytes of galactosaemic children and their families and in normal controls. Parents of galactosaemic children have about 64 % of the enzyme activity found in controls, while homozygous individuals have little or none. There is a slight overlap of enzyme levels in the control and heterozygote groups. This renders a definite placing of borderline cases impossible.There is some evidence to suggest that the quantitative differences between heterozygotes are not indicative of different genotypes. The possible existence of different genetic variants, whose phenotypical expression is the same, have been discussed.We would like to record our gratitude to the Board of Governors, United Manchester Hospitals, for a maintenance grant to one of us (A.R. W.) and for defraying costs of reagents and other incidental expenses; to Profs. W. Gaisford and A. C. P. Campbell for their unfailing support; to Prof. Sir Robert Piatt and Prof. H. Harris for reading the manuscript and offering valuable advice; to Dr A. H. Gowenlock for assistance with the statistical evaluation of the results; and to many Paediatricians and Pathologists all over the British Isles for their co‐operation with us in securing specimens from their patients. We would also like to thank Mr E. G. Smith and the Department of Medical Illustration of the Manchester Royal Infirmary for the preparation of the illustrations.

Screening for Galactosemia in New York State

“…"Classic galactosemia," that is, infants with appropriate clinical signs at the time physicians were notified of abnormal screening results (by telephone on the day of the test, if strikingly abnormal), was certain in two of the 141,402 infants, giving an incidence of one in 70,000. This frequency was remarkably similar to an early estimate of the incidence of galactosemia at birth in Great Britain (15), projected from clinical reports of the disease.…”

Galactosaemia: results of the British Paediatric Surveillance Unit Study, 1988-90.

“…There was one death in this group, that of the patient referred to earlier who died from E coli septicaemia at 4 days. Three siblings of the study patients died of liver disease around 6 weeks of age and were presumed affected. Two came from areas that were being screened at the time of their birth, but it could not be confirmed that neonatal screening had been performed in these cases.…”

Detection of heterozygotes for galactokinase deficiency in a human population

“…The metabolic lesion in this disorder is the absence of transferase activity (Isselbacher et aL, 1956). Heterozygotes for galactosemia have approximately one-half the activity of transferase in blood cells as normal individuals and there is very little overlap between the heterozygous range and the normal range (Kirkman and Bynum, 1959;DonneU et al, 1960;Hsia et al, 1960;Schwarz et al, 1961 ;Weinberg, 1961). Therefore, it is possible to determine the frequency of heterozygous individuals in the general population by measuring transferase in blood cells (Hansen et al, 1964;Beutler et al, 1966;Brandt, 1967;McGuiness and Saunders, 1967).…”