Human Reproduction Update Advance Access published online on September 30, 2009
Human Reproduction Update, doi:10.1093/humupd/dmp038
Gonadal function in male and female patients with classic galactosemia
1 Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands 2 Department of Genetic Metabolic Diseases Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands 3 Department of Clinical Chemistry, Maastricht University Medical Center, Maastricht, The Netherlands 4 Department of Obstetrics and Gynaecology, University Medical Center Groningen, Groningen, The Netherlands
To whom correspondence should be addressed at: 5 Correspondence address. Department of Pediatrics and Genetic Metabolic Diseases Laboratory, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands. E-mail: estela.rubio{at}mumc.nl
BACKGROUND: Hypergonadotropic hypoestrogenic infertility is the most burdensome complication for females suffering from classic galactosemia. In contrast, male gonadal function seems less affected. The underlying mechanism is not understood and several pathogenic mechanisms have been proposed. Timing of the lesion, prenatal or chronic post-natal, or a combination of both are not yet clear.
METHODS: This review focuses on gonadal function in males and females, ovarian imaging and histology in this disease. It is based on the literature known to the authors and a Pubmed search using the keywords galactosemia, GALT deficiency, (premature) ovarian failure/insufficiency/dysfunction, testicular function, gonadotrophins, FSH, LH (published between January 1971 and April 2009).
RESULTS: Male gonads are less affected, boys spontaneously reach puberty, although onset can be delayed. Semen quality has not been extensively studied. Several affected males are known to have fathered a child. Female gonads are invariably affected, although to a varied extent (hypergonadotropic hypoestrogenic ovarian dysfunction). Intriguingly, FSH is often already increased in infancy. Imaging usually shows hypoplastic and streak-like ovaries. Histological findings in some cases reveal the presence of morphologically normal but decreased numbers of primordial follicles, with the absence of intermediate and Graafian follicles.
CONCLUSION: Gonads in males seem less affected than in females who exhibit hypergonadotropic hypoestrogenic subfertility. FSH can be elevated in infancy, and ovarian histology sometimes shows the presence of normal primordial follicles with absence of intermediate and Graafian follicles. These findings are similar to other genetic diseases primarily affecting the ovary.
Key words: galactosemia / gonads / ovarian dysfunction / testicular function / FSH
Received on April 29, 2009; revised July 24, 2009; accepted on August 21, 2009