Related Experiment Videos
Endocrinology of the carbohydrate-deficient glycoprotein syndrome type 1 from birth through adolescence
1Department of Pediatrics, University of Leuven, Belgium.
Insights
Carbohydrate-deficient glycoprotein syndrome type 1 (CDG) impacts endocrine function, causing age-dependent hormonal changes including hypergonadotropic hypogonadism and thyroid axis abnormalities. This study highlights the critical role of glycoprotein glycosylation in pediatric endocrinology.
Area of Science:
- Pediatric Endocrinology
- Glycoscience
- Genetic Disorders
Background:
- Carbohydrate-deficient glycoprotein syndrome type 1 (CDG) is a genetic disorder affecting glycoprotein structure.
- CDG syndrome is characterized by multisystemic involvement, notably neurologic impairment.
- The endocrine system's role in CDG remains incompletely understood.
Purpose of the Study:
- To investigate the endocrine status in patients with CDG syndrome type 1.
- To characterize age-dependent hormonal changes and their implications.
- To elucidate the impact of impaired glycosylation on various endocrine axes.
Main Methods:
- Diagnosis of CDG syndrome type 1 confirmed by immune-isoelectric focusing of serum sialotransferrins.
- Comprehensive endocrine assessment including hormonal levels and responses to stimulation.
- Longitudinal follow-up of patients over 16 years.
Main Results:
- Elevated serum FSH and LH levels observed in prepubertal and adolescent patients.
- Low estradiol levels in adolescent girls despite normal ovarian response to exogenous gonadotropins.
- Thyroid axis abnormalities included thyroid-binding globulin deficiency and transient hyperthyrotropinemia.
- Subnormal testicular volume in males and paradoxical growth hormone response in adolescents.
- Decreased transcortin and lower-normal IGF-1 levels.
Conclusions:
- CDG syndrome type 1 presents with an age-dependent endocrine profile, including hypergonadotropic hypogonadism.
- Deficient FSH action and transient hyperthyrotropinemia are key findings.
- Impaired glycoprotein glycosylation significantly affects pediatric endocrine function.
Abstract:
The carbohydrate-deficient glycoprotein (CDG) syndrome type 1 is a genetic multisystem disorder, characterized by hypoglycosylation of glycoproteins and presenting with neurologic impairment. In 12 girls and 14 boys, we confirmed the diagnosis of CDG syndrome type 1 by immune-isoelectric focusing of serum sialotransferrins, and we examined the endocrine status singly or sequentially, including a 16-y follow-up of the index cases, a pair of monozygotic girls. Serum FSH levels were normal in newborns and prepubertal children, but elevated in female toddlers and teenagers, as well as in adolescent males. Serum LH concentrations displayed an analogous age-dependent pattern. In adolescent girls, serum estradiol remained low. FSH bioactivity was low normal, as was the bioactive/immunoreactive FSH ratio. However, exogenous gonadotropins evoked an estradiol response and induced ovarian follicular growth. Male patients virilized at puberty; however, testicular volume was subnormal. The thyroid axis was hallmarked by thyroid-binding globin deficiency and, during infancy, increased serum TSH concentrations. A subgroup of female patients presented hypersomatotropism and/or hyperprolactinemia. During adolescence, the index cases responded to glucagon with normal glycemic, but exaggerated insulin and paradoxically augmented growth hormone responses. The hypothalamo-pituitary area appeared intact on magnetic resonance imaging. Circulating IGF-1 levels were in the lower normal range and transcortin concentrations decreased. In conclusion, a study of endocrine aspects of a major glycosylation disorder revealed an age-dependent constellation, including hypergonadotropic hypogonadism with deficient FSH rather than LH action; transient hyperthyrotropinemia; inconsistent hyperprolactinemia; hyperglycemia-induced growth hormone release; deficiencies of hormone-binding glycoproteins and possibly decreased insulin sensitivity, thus pointing to the importance of glycoprotein glycosylation for pediatric endocrinology.