Abnormalities of carbohydrate metabolism and of OCT gene function in the Rett syndrome.
The pathogenetic basis of the Rett syndrome (RS) is unknown: an X-linked dominant, male-lethal gene defect is thought likely. We present a girl with RS who has defects both of the urea cycle and of carbohydrate metabolism resulting in fasting hypoglycaemia, post-prandial hyperlactataemia and excess urinary orotic acid excretion after alanine load. Her sister has a similar clinical picture, but less marked metabolic anomalies. The mother of these sisters has abnormal urinary orotic acid excretion; she transmitted opposite ornithine carbomoyltransferase (OCT) alleles to the two girls. Another girl with RS has similar metabolic responses to fasting and to carbohydrate load. We conclude that RS may be an aetiologically homogeneous condition, but that it includes a variable pattern of metabolic anomalies, and that the gene defect is distinct from the OCT locus.
Clarke
A
A
Department of Human Genetics, University of Newcastle upon Tyne, Wales, England.
Gardner-Medwin
D
D
Richardson
J
J
McGann
A
A
Bonham
J R
JR
Carpenter
K H
KH
Bhattacharya
S
S
Haggerty
D
D
Fleetwood
J A
JA
Aynsley-Green
A
A
D000293:Adolescent; D050260:Carbohydrate Metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008659:Metabolic Diseases / Q000209:etiology*; D009954:Ornithine Carbamoyltransferase / Q000235:genetics; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D014508:Urea / Q000097:blood*
D014508:Urea; D009954:Ornithine Carbamoyltransferase