Variant Without Pseudoglioma in a Young Man With Fragility Fractures.

Osteoporosis in children and young adults is relatively rare. Hereditary causes are often overlooked in the absence of a positive family history. We report a 29-year-old male presenting with recurrent fragility fractures since 6 years of age. Secondary causes, such as celiac disease, inflammatory disorders, and hypogonadism, were ruled out. Family history was negative for any bone disease. Exome sequencing revealed 2 variants of gene-intron 5 c.1015 + 1G > A and exon 5 c.892C > T. Although the former variant has been described in literature as a cause of osteoporosis in homozygous state only, it manifested as osteoporosis in our patient, in the heterozygous state, in presence of a second variant of uncertain significance. However, eye involvement, which is classically seen in "osteoporosis-pseudoglioma syndrome" homozygote, was absent in our patient. Genetic analysis of the parents revealed father to be a carrier of intron 5 c.1015 + 1G > A and mother exon 5 c.892C > T variants of the gene. However, none of them had osteoporosis on bone densitometry. The patient was subsequently treated with IV zoledronic acid (planned to be administered annually) and showed improvement in bone density by 11% at the spine and 9.5% at the left femur; there were no further fractures over 1 year of follow-up.