Osteoporosis Pseudoglioma with Hypergammaglobulinemia: A Rare Case

Introduction : The balance between osteoclasts and osteoblasts determines the efficacy of bone remodeling. Osteoblastic bone formation is under the control of the WNT (wingless signaling pathway). WNT agonists bind to the low density lipoprotein receptor 5 and 6 (LRP5/6) receptor on osteoblasts to stimulate bone formation. Mutation of genes that code LRP5 function may cause osteoporosis pseudoglioma. We present a young woman with retinopathy and osteoporosis due to osteoporosis pseudoglioma.

Case Description : A 39-year-old female was seen in endocrinology clinic with history of a fracture of L4 at age nine and severe visual problems. Her eyes at birth showed proliferative retinopathy and exudative retinal detachment occurred soon after birth in her left eye. She had laser and cryosurgery at the age of nine years. Her right eye did not respond to multiple surgeries, but her left eye responded well. She had normal psychomotor development. No investigation was done to evaluate the cause of the lumbar fracture.

She was born of a non-consanguineous marriage and there was no family history of bone abnormalities. At the age of 29 years, she was found to have polyclonal hypergammaglobulinemia and was admitted to the myeloma unit for gene analysis and bone marrow biopsy. Urine and plasma protein electrophoresis were negative for multiple myeloma. Bone marrow biopsy was negative for B cell lymphoma, proliferative disorders, and plasma dyscrasias. Dexa scan showed a T score of –5.2 at lumbar spine, -2.9 at left femoral neck and –3.1 at right femoral neck. She was found to have a mutation in LRP5 on chromosome 11. Serum calcium was 9.8 mg, parathyroid hormone (PTH) 27 pg/mL, creatinine 0.5 mg/dl, alkaline phosphatase 114 U/L, and vitamin D 21 ng/ml. She received 50,000 international units/wk of vitamin D3.
Because PTH analogs can abrogate the effect on protein kinase B (Akt) phosphorylation and WNT signaling, teriparatide was initiated at the age of 30. After two years, her density on the posteroanterior view of L1-L4 increased by 21.1% and on the lateral projection of L3 by 34.7%.

Discussion : Several conditions such as osteogenesis imperfecta, Liberfarb syndrome and osteoporosis pseudoglioma can present with visual impairment but not all patients with osteoporosis pseudoglioma are blind. The bone manifestations appear later in life, but the patients have vision problems from birth or at an early age. It is important to remember the connection of eye disorders with osteoporosis, especially since treatment of osteoporosis pseudoglioma with teriparatide may be quite rewarding.