Abstract
Disclosure: R.M. Tuska: None. M. Brush: None. A.A. Livinski: None. R.J. Brown: None. Congenital Generalized Lipodystrophy (CGL) is characterized by a near-total loss of subcutaneous adipose tissue, leading to severe metabolic and systemic comorbidities. CGL is most commonly caused by mutations in AGPAT2 (CGL1) and BSCL2 (CGL2) genes. Skeletal abnormalities such as diffuse sclerosis, lytic bone lesions, and high bone mineral density (BMD) have been recognized in many patients with CGL, but the radiologic and clinical features of these bone phenotypes remain ill-defined. The aim of this systematic review was to evaluate the bone manifestations and radiologic findings associated with CGL1 and CGL2. We searched 6 databases: CINAHL Plus, Embase, Global Index Medicus (WHO), PubMed, Scopus, and Web of Science: Core. We screened articles utilizing a dual reviewer process in Covidence. Included publications reported primary bone and radiologic findings in patients with CGL1 or CGL2. Exclusions comprised publications without full text, duplicate publications, those lacking bone measures, and review articles. Two reviewers extracted data using RedCap and assessed risk of bias. 270 records were screened and 37 records reporting 179 cases of CGL were included for data extraction. Among the 79 patients assessed for bone cysts, 49 (62%) exhibited lytic appearing lesions. Of these 49, 14 (29%) patients presented with symptomatic lesions, primarily manifesting as bone pain at the lesion site (n=6), or pathologic fracture at the lesion site (n=9). Bone biopsy (n=7) revealed thin trabeculae and extensive vascular proliferation at the lesion site. Bone marrow biopsies (n=2) and imaging (n=20) revealed normal hematopoietic marrow with a marked reduction in marrow fat. 12 patients underwent serial bone imaging revealing diffuse osteosclerosis and the absence of lytic lesions in early childhood. During adolescence, lytic lesions appeared and progressed throughout the proximal and distal ends of the long bones in the appendicular skeleton sparing the axial skeleton. Markers of bone turnover were within normal limits except for sclerostin, which was elevated in a cohort of 11 patients. High BMD (n= 65), advanced skeletal maturation (n= 49), diffuse osteosclerosis (n=30), scoliosis (n=8), pseudo-osteopoikilosis (n=6), coxa valga (n=5), enlarged epiphyses (n=7), and coarse trabeculae (n=8) were also reported. While leptin replacement therapy improved metabolic parameters in many patients, it did not reverse the high bone mineral density or significantly alter markers of bone turnover. Individuals with CGL exhibit a spectrum of skeletal abnormalities including lytic-appearing lesions, osteosclerosis, high bone mineral density, advanced skeletal maturation, and pseudo-osteopoikilosis. Further long-term follow-up is needed to comprehensively assess the progression of these lesions over the life course and to elucidate the mechanisms contributing to their development. Presentation: 6/2/2024