Karlberg S, et al. - Researchers investigated the timing of onset and clinical course of premature ovarian insufficiency (POI) in patients with Mulibrey nanism (MUL), a monogenic disorder caused by mutations of the peroxisomal TRIM37 gene. Infant and young MUL girls already display a highly reduced number of ovarian follicles. The majority of these patients would have early depletion of follicles resulting in clinical and biochemical signs of POI.

Methods

• In 33 MUL patients [aged 5.1–47.3 years (median age 22.3) at the end of observation], the gonadal function, pubertal development and ovarian reserve were studied.
• Between 2004 and 2014, they followed the patients and enrolled 19 pubertal or postpubertal patients in a cross-sectional study.
• Longitudinal assessment was performed of the period of postnatal activation of the hypothalamic–pituitary–gonadal axis (minipuberty), pubertal development and menstrual history.
• In this cross-sectional study, they performed gynecological examination, analysis of reproductive hormones and ultrasonography with evaluation of ovarian volume and antral follicle count.

Results

• A transient minipuberty with a high FSH surge was observed in infant girls.
• Gonadotropins were normal or slightly elevated in childhood, but these began to rise to hypergonadotropic levels in prepuberty.
• Throughout childhood, undetectable or low anti-müllerian hormone (AMH) levels were noted.
• Spontaneous onset of puberty occurred; the median age at menarche was 12.5 years.
• Regular menses was never attained in 54% of the patients; only 8% of the women menstruated regularly 10 years from menarche.
• In the cross-sectional study, ultrasonography revealed normal ovarian morphology in none of the patients.
• Ovaries were hypoplastic; no or fewer than two visible antral follicles were noted in 82%.
• The vast majority (89%) demonstrated undetectable AMH levels.