ESPE Abstracts

Background: GM1 gangliosidosis falls in the category of endogenous metabolic disorders and is characterized by β-galactosidase deficiency. It is inherited in an autosomal recessive manner and is characterized by neurodevelopmental deficits, generalized hypotonia, dystonia and the presence of convulsions and also skeletal malformations such as a prominent forehead, kyphoscoliosis, brachydactyly and joint flexions. The association of the disease with growth hormone deficiency has been found and studied so far only in animals, while no corresponding clinical case in humans has been published. However, the assumptions made about the possible mechanism may be the same in both species.

Case Presentation: A 9^7/12year-old boy was referred for evaluation to the Pediatric Endocrinology Unit because of a reported microphallus. The child has been monitored by the Pediatric Neurology Unit of the same hospital due to a genetic diagnosis of GM1 gangliosidosis type 2 for two years and treated with miglustat and a ketogenic diet.The child presented with microphallia (penile length=4.5cm <3^rd percentile) and growth delay (Height :124cm, <3^rd percentile) with an average growth rate of 2.4cm/year for the last two years concomitantly with insufficient body weight increase. The child was Tanner stage I and hormonal investigation revealed a very low IGF-1 value (33.3ng/ml) with the rest of hormonal tests being within normal values. The patient underwent two consecutive growth hormone stimulation tests, which were abnormal (peak GH in glucagen test = 2.89ng/ml and peak GH in L-Dopa test=4.59ng/ml). A diagnosis of growth hormone deficiency was made. Pituitary MRI was normal

Conclusion: We report the case of a boy with GM1 gangliosidosis and growth hormone deficiency. Endogenous metabolic disorders may affect growth both by direct effects on the GH/IGF-1 pathway and through renal and hepatic insufficiency. Our patient diagnosed with GM1 gangliosidosis and GH deficiency (GHD) had normal kidney and liver function. Moreover, the association of GM1 with GHD has been observed in animals in which administration of exogenous recombinant GH increased serum IGF-I levels, indicating that GH/IGF-I signaling pathways within the liver remain intact and suggesting that alterations are external to the liver.