Background: Osteoporosis-pseudoglioma syndrome (OPPG), rare autosomal recessive entity, is characterized by juvenile osteoporosis, bone deformities, neuromotor retardation, and congenital blindness. This syndrome is due to the loss-of-function mutation in LRP5 (Low-density lipoprotein receptor-related protein 5). Here report four cases from three families, with confirmed molecular diagnosis who showed improvement of osteoporosis improved with biphosphonate therapy.
Case reports: Four patients were followed-up at medical genetics, neurology and ophthalmology clinics due to congenital blindness and neuromotor retardation including a 6.5-year-old girl [case 1], two siblings: a 7-year-old girl [case 2] and a 3-year-old boy [case 3], and a 2.5-year-old boy [case 4]) were referred to our clinic for assessment of osteoporosis. All patients had born at term, appropriate for gestational age to consanguineous parents, and vision disorders were noted at around postnatal 2nd week. At presentation, cases 1 and 2 had fractures after mild trauma, case 3 had no fracture and case 4 had fractures at follow-up. Heights SDS of the all patients were within target height ranges. Mental retardation, microphthalmia, corneal opacity and bone deformities such as dorsal kyphosis, pectus excavatus were present in all of the patients. Stereotypic movements were observed in cases 3 and 4. Case 1 was wheelchair-bound since age-four, and others were able to walk with assistance. In all cases, levels of serum calcium, phosphorus, creatinine, alkaline phosphatase, parathormone, 25 OH vitamin D, urinary calcium/creatinine and urinary USG were normal. Bone mineral density (BMD) measurements on DEXA, expressed as z-scores were found as −6.0, −6.9, −2.6 and −4.3 respectively. In all cases, mutations in LRP5 gene confirmed the diagnosis. All patients were given vitamin D and oral calcium, and pamidronate infusion was started in all cases varying from 3 to 6 months intervals. Follow-up period of case 1 was twelve years, and in other patients three years. On biphosphonate therapy, improvements in BMD were observed in all patients. BMD z-scores showed an improvement to −1.3, −3.7, 1.8, and −3.6 respectively.
Conclusion: Osteoporosis-pseudoglioma syndrome should be taken into consideration in patients where osteoporosis is accompanied by congenital ocular findings. Osteoporosis is an expected finding of the disease which shows an improvement with biphosphonate treatment.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology