한국인 Lowe syndrome 환자의 임상 및 분자 유전학적 고찰
Lowe Syndrome: A Single Center’s Experience in Korea
Abstract
Background: Lowe syndrome is a rare X-linked recessive disorder caused by mutations in the OCRL gene. It involves multi-systems, particularly the eyes, central nervous system, and kidneys, leading to profound growth failure and global developmental delay. Objectives: This study was undertaken to evaluate the clinical and genetic characteristics of Korean patients with Lowe syndrome. Methods: The clinical findings and the results of genetic study were reviewed for 12 male patients diagnosed with Lowe syndrome in a single institution from December 1991 to April 2013. Results: Mean age at presentation was 2.2 months of age (0 ~ 4 months of age), but the diagnosis was delayed by 34.1 months (0 ~ 116 months). The mean follow-up period was 0.6 years to 16.7 years (mean 9.0 ± 5.6 years). Nine different OCRL mutations were identified in 11 patients (92%). Three novel mutations were identified. The main presenting sign was bilateral congenital cataracts, necessitating early removal of cataracts in 11 patients with impaired visual acuity in all these patients. Profound short stature and developmental delay were observed in all the subjects, and seizure occurred in 50% of the patients. All patients suffered from proximal renal tubular dysfunction. A patient ended up with chronic renal failure. Other manifestations include pathologic bone fracture (50%), cutaneous cysts (42%), and cryptorchidism (42%). The increased bleeding tendency was not found in our patients. Mainstay of therapy was related to renal tubulopathy and its complications including renal rickets and nephrocalcinosis. None of the subjects died during the study period. Conclusion: In this study, we described the detailed clinical and genetic characteristics of Lowe syndrome in Korea. These observations help to understand the natural courses of Korean patients with Lowe syndrome and to provide an appropriate genetic counseling.