Background: Osteoporosis-pseudoglioma (OPPG) syndrome is an autosomal recessive disorder characterised by severe juvenile osteoporosis and congenital or infancy-onset visual loss. OPPG is caused by loss of function mutations in LDL receptor-related protein 5 (LRP5) gene. We present a 13-year-old child with a homozygous mutation in LRP5 and low bone mass but without visual loss.
Presenting problem/clinical management: This child presented with multiple low trauma fractures and baseline bone mineral density at the lumbar spine was 0.759 g/cm2 (age matched Z-score of −2.0) prior to treatment with cyclical intravenous bisphosphonates. Ophthalmology assessment detected retinal folds and myopia (0.56 on the LogMAR scale). Functionally the patient was able to attend normal school, read and travel on public transport without support.
The LRP5 gene was analysed and found to be homozygous for the sequence variant c1517A>T predicted to result in a p.Asn506lle amino acid change. Both parents were non affected heterozygous carriers.
Discussion: Mutations in the LRP5 gene are known to be associated with skeletal disorders: gain of function mutations lead to high bone mass; loss of function mutations results in OPPG and heterozygous mutations can result in primary osteoporosis. The homozygous mutation in this patient was in the highly conserved YWTD motif and supported the diagnosis of OPPG. Most patients with OPPG are blind by 15 years of age; however, this patients visual impairment only caused mild functional compromise. Whilst further functional studies are needed, this unusual case of mild visual impairment in a patient with OPPG is important in furthering our understanding of genotype-phenotype correlations in this disease.
22 - 25 Jun 2013