RESUMO
UNLABELLED: The risk for premature ovarian failure (POF) in females with galactosemia can be predicted by analyzing 3 areas of risk pathology: the patient's molecular genotype for galactose-1-phosphate uridyltransferase (GALT), alternate pathways for galactose metabolism, and the patient's environment at diagnosis and during treatment. STUDY DESIGN: Retrospective cross-sectional information was collected on 53 females with classic galactosemia, and their ovarian function was analyzed by determination of serum follicle-stimulating hormone and luteinizing hormone levels and by clinical observation. The associations were analyzed between POF and the mutations in GALT, the highest erythrocyte galactose-1-phosphate (Gal-1-P) level at diagnosis, the age at which dietary treatment was initiated, mean erythrocyte Gal-1-P level during treatment, and whole-body carbon 13-labeled galactose oxidation to (13)CO(2). RESULTS: The most prevalent mutation, Q188R, had a significant effect of genotype category (Q188R/Q188R, Q188R/Other, Other/Other) on POF (P =.04, Fisher exact test and an odds ratio of 8.3). Mean erythrocyte Gal-1-P level during treatment was a significant risk factor for POF (P =.04). Also, all patients studied with less than 5% total body oxidation of galactose to (13)CO(2) had POF, whereas those with more than 5% did not have POF (P =.008, Fisher exact test). CONCLUSION: The development of POF in females with galactosemia is more likely if the patient's genotype is Q188R/Q188R, if the mean erythrocyte Gal-1-P is >3.5 mg/dL during therapy, and if the recovery of (13)CO(2) from whole-body (13)C-galactose oxidation is reduced below 5% of administered (13)C-galactose.
Assuntos
Galactosemias/complicações , Insuficiência Ovariana Primária/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Hormônio Foliculoestimulante/sangue , Galactosemias/dietoterapia , Galactosemias/genética , Genótipo , Humanos , Lactente , Mutação Puntual/genética , Insuficiência Ovariana Primária/diagnóstico , Insuficiência Ovariana Primária/epidemiologia , Estudos Retrospectivos , Fatores de Risco , UTP-Hexose-1-Fosfato Uridililtransferase/sangue , UTP-Hexose-1-Fosfato Uridililtransferase/genéticaRESUMO
133 patients with congenital or idiopathic cataracts were studied (94 patients had ages between 1 month and 14 years; 10 patients had ages between 16 and 50 years and 29 patients did not have an age registry) along with 18 patients with a clinical diagnosis of classic galactosemia. The activity of galactokinase (GALAK) and that of erythrocyte galactose-1-phosphate uridyl transferase (GALT) was measured. There were no individuals with a total deficiency of GALK or GALT. The cataract patients of ages between 1 monthly and 14 years, 3 (3.19%) and 4 (4.25%) showed GALK and GALT levels in the range corresponding to the respective heterozygotes. As compared with the expected incidence of heterozygotes in the general population (0.2% for GALK and 0.8% for GALT) we found a significant rise of individuals with low levels of enzymes for the metabolism of galactose. The possibility that heterozygote galactosemic states contribute a risk factor in the development of cataracts and its therapeutic implications are discussed.
Assuntos
Catarata/etiologia , Galactoquinase/deficiência , Galactose/metabolismo , Galactosemias/diagnóstico , UTP-Hexose-1-Fosfato Uridililtransferase/deficiência , Adolescente , Adulto , Catarata/congênito , Catarata/enzimologia , Catarata/genética , Criança , Pré-Escolar , Galactoquinase/sangue , Galactosemias/complicações , Galactosemias/epidemiologia , Galactosemias/genética , Frequência do Gene , Triagem de Portadores Genéticos , Humanos , Incidência , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Fatores de Risco , UTP-Hexose-1-Fosfato Uridililtransferase/sangueRESUMO
The first recognized case of a Rennes-like variant form of galactosemia in a Caucasian individual is described. Galactose-1-phosphate uridyl transferase activity was approximately 10% of the normal in both erythrocytes and cultured skin fibroblasts. Electrophoretic mobility of the variant enzyme in erythrocytes was slower than that of normal individuals and identical to that of the two cases originally reported from Rennes, France. In normal cultured skin fibroblasts, four transferase bands were found. In this tissue, the patient again had a slower moving transferase. It is proposed that in transferase variants an altered subunit results in a specifically altered enzyme mobility analogous for each tissue.