Altered follicle stimulating hormone isoforms in female galactosaemia patients

Many women affected with galactosaemia suffer from ovarian dysfunction and have elevated serum levels of follicle stimulating hormone (FSH). We have analysed FSH-glycoprotein isoforms from four galactosaemic and five healthy women. Besides the commonly found FSH species with a median isoelectric point (pI) of 4-5, the sera of the female galactosaemic patients contained qualitatively abnormal FSH isoforms with a pI close to neutral (6.4-7.0). The generally reduced galactosylation in patient samples was confirmed because sera of galactosaemic patients could incorporate 1.7 times more UDP-(14C)galactose than did healthy subjects.

Our data indicate that the terminal disaccharides of FSH (a glycoprotein), galactose and sialic acid were partially deficient in three galactosaemic female patients with no galactose-1-phosphate uridyl transferase (GALT) activity in red cells. However, from a female patient with a residual GALT activity (a mild form of galactosaemia), no distinctive deficiency was observed. This again suggest an importance of GALT in retaining a correct FSH structure. Therefore the abundance of neutral FSH isoforms, which was described to have a higher binding affinity to its receptor and no capacity to activate cyclic adenosine mono-phosphate (cAMP), may cause a hormonal dysfunction in classical galactosaemia.