Vaghasia Nupoor, Dutta Aditya, Mithal Ambrish
Institute of Endocrinology and Diabetes, Max Healthcare, Saket, New Delhi 110017, India.
JCEM Case Rep. 2024 Sep 20;2(10):luae163. doi: 10.1210/jcemcr/luae163. eCollection 2024 Oct.
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.
儿童和青年骨质疏松症相对罕见。在没有阳性家族史的情况下，遗传原因常常被忽视。我们报告一名29岁男性，自6岁起反复出现脆性骨折。排除了继发性原因，如乳糜泻、炎症性疾病和性腺功能减退。家族史中无任何骨病。外显子组测序揭示了该基因内含子5的2个变异，即c.1015 + 1G > A和外显子5的c.892C > T。尽管前一个变异在文献中仅被描述为纯合状态下骨质疏松症的病因，但在我们的患者中，在杂合状态下，在存在另一个意义不确定的变异时，它表现为骨质疏松症。然而，我们的患者没有出现典型的“骨质疏松-假性胶质瘤综合征”纯合子所见的眼部受累情况。对其父母的基因分析显示，父亲是该基因内含子5 c.1015 + 1G > A的携带者，母亲是外显子5 c.892C > T变异的携带者。然而，他们通过骨密度测定均未发现骨质疏松症。该患者随后接受了静脉注射唑来膦酸治疗（计划每年给药），脊柱骨密度提高了11%，左股骨提高了9.5%；在1年的随访中未再发生骨折。
