Endocrine Abstracts

Introduction: Osteogenesis imperfecta (OI) is a rare, heterogeneous, genetic connective tissue disorder that manifests clinically as bone fragility, brittleness and growth disorder. Effective diagnosis is important (although often challenging) to enable institution of early and effective multidisciplinary management.

The case: A 19-year-old woman was referred to the Endocrine clinic at the Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM, UHCW) following a low-impact fall resulting in fractures of her pelvic rami. Her past medical history revealed numerous childhood low-impact fractures, a prior eating disorder and poor hearing. There was no family history of note. Her only medication was the combined oral contraceptive pill (microgynon), and she was a smoker. On examination, her BMI was 17.9 kg/m². She had blue discolouration to her sclerae bilaterally, bilateral clinodactyly and increased joint laxity. Weber’s test localised to the right-side. Serum calcium, magnesium, phosphate, alkaline phosphatase and 25-hydroxycholecalciferol levels were all normal. Pelvic X-rays confirmed fractures to the superior and inferior rami. DEXA bone scan revealed lumbar osteopenia (T-score −1.8).

Genetics: Sequencing genomic DNA revealed that she is heterozygous for the c.3880_3883dup mutation in exon 50 of the COL1A1 gene, confirming our clinical suspicion of OI Type 1. This mutation is predicted to result in a frameshift at p.Thr1295, and truncating stop codon 3 amino acids downstream. This mutation has not previously been reported in OI. She has ongoing genetics and audiology follow-up, has been commenced on a bisphosphonate and has been advised regarding modifications to her lifestyle.

Conclusions: We report a novel frameshift mutation within COL1A1 resulting in OI in a young woman who had sustained numerous childhood low-trauma fractures. Despite her classical blue sclerae, the diagnosis of OI had not previously been entertained. This case illustrates the importance (and challenges) of early diagnosis and effective management of OI.

DOI: 10.1530/endoabs.31.P13