Leptin Levels in Children and Adults with Classic Galactosaemia

Abstract

Among the long-term complications of Classic Galactosaemia (Gal) is premature ovarian insufficiency (POI) in female patients with subtle abnormalities of reproductive function also reported in male patients. Leptin is a circulating hormone which reflects body energy stores and which affects the neuroendocrine reproductive axis and pubertal development.We measured serum leptin in 28 children (10 girls, 18 boys; mean age 7.6 years, range 0.5-17.9 years) and in 22 adults (10 females, 12 males; mean age 23.9 years, range 18-37 years) with Gal on a strict galactose-restricted diet in comparison with control data.Leptin levels (expressed as SDS for gender and pubertal stage) were lower in Gal children than controls (mean leptin-SDS ¼ -0.71 for girls, p < 0.05, -0.97 for boys compared with SDS ¼ 0 for controls, p < 0.05). In an age-related analysis, leptin levels did not correlate with age in children with Gal for both sexes as it did for matched controls.As expected, females had higher leptin levels than males in either group. In adults with Gal, leptin concentrations were within normal limits for both sexes when adjusted for gender and BMI. There was a linear relationship between log-leptin and BMI in children with Gal and in controls. For Gal women, log-leptin was also associated with BMI. However, for Gal men, and hence for the entire group of adult Gal patients, this association between log-leptin and BMI was not detectable. Our findings suggest that leptin dysregulation may play a role in fertility issues in individuals with Gal from an early age.

Effects of temporary low-dose galactose supplements in children aged 5–12 y with classical galactosemia: a pilot study

“…We have also demonstrated that the metabolic hormone leptin is lower in girls and boys with galactosemia than in healthy controls when adjusted for gender and pubertal stage (9). Leptin, a member of the cytokine family, is predominantly produced in adipocytes but to a much lesser extent also found in stomach, kidney, liver, and other cells, a process which can be stimulated by, for example, insulin and corticosteroids (10).…”

N-Glycan Abnormalities in Children with Galactosemia

“…It is recognized that hyperglycosylation of a number of pharmacologically relevant proteins such as leptin 57 and follicle stimulating hormone (FSH) has been shown to increase the in vivo activity of the proteins. 58 From our previous studies 6 and our recent report of leptin dysregulation in galactosemia, 59 it is reasonable to propose that the N-glycan processing defects observed with IgG analysis in these patients may be also evident in many functional systemic glycoproteins, glycolipids, and receptors, even in treated galactosemia patients.…”

Systemic gene dysregulation in classical Galactosaemia: Is there a central mechanism?

“…It has also been reported to have a potential neuroprotective role and disruption of leptin signalling may have a role in cognitive defects [37][38][39][40]. Of note, we have recently described altered leptin levels and hypoleptinaemia in patients with Galactosaemia [41].…”