P.004 Endocrine and growth abnormalities in 4H leukodystrophy patients with a molecular diagnosis

Abstract

Background: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder characterized by hypomyelination, hypodontia and hypogonadotropic hypogonadism caused by mutations in POLR3A, POLR3B and POLR1C. The endocrine abnormalities have never been systematically studied. Methods: A cross sectional international multicenter study was performed and the following variables were assessed: weight, height, head circumference, pubertal history, hormone levels and neurological and non-neurological features. Data was analyzed to determine whether there was a correlation between the presence of endocrine abnormalities and mutations in a specific gene and/or the presence of specific symptoms such as other non-neurological symptoms. Results: Data was collected on 156 patients. Endocrine data were available for 144 patients. The most common endocrine abnormalities seen in this cohort were short stature (54/90 patients (60%)) and delayed puberty (53/70 patients (76%)). 13 of the 58 patients tested (22%) had abnormal thyroid function. Patients with POLR3A mutations were more likely to have endocrine abnormalities. Conclusions: Our results confirm that the most common endocrine features in 4H leukodystrophy are short stature and pubertal abnormalities. However, the other potential endocrine abnormalities are typically under-investigated in this patient population. A prospective study is required to investigate the extent and severity of the endocrine abnormalities in 4H leukodystrophy.