Heterogeneity and high prevalence of bone manifestations, and bone mineral density in congenital generalized lipodystrophy subtypes 1 and 2.

Introduction: Congenital Generalized Lipodystrophy (CGL) is a rare autosomal recessive disease caused by mutations in genes responsible for the formation and development of adipocytes. Bone abnormalities are described. However, there is a scarcity of data. Objective: To describe bone characteristics in a large CGL1 and 2 case series. Methods: Cross-sectional study that assessed bone radiological features of CGL patients of a reference hospital in Fortaleza (CE), Brazil. Patients underwent clinical and bone mineral metabolism evaluation, radiographs of the axial and appendicular skeleton and bone mineral density (BMD) assessment by DEXA (dual energy X-ray absorptiometry). Results: Nineteen patients were included, fourteen were CGL1 and 5, CGL2. Median age was 20 years (8-42) and 58% were women. Median BMI and percentage of body fat were, respectively, 21 Kg/m² (16-24), and 10.5% (7.6-15). The median leptin concentration was 1 ng/mL (0.1-3.3). Diabetes mellitus and dyslipidemia were present in 79% and 63% of patients, respectively. Median calcium and phosphate were normal in almost all patients (95%). Median parathyroid hormone and 25-OH-vitamin D were 23 pg/mL (7-75) and 28 ng/mL (18-43). Osteolytic lesions, osteosclerosis and pseudo-osteopoikylosis, were present in 74%, 42% and 32% of patients, respectively. Lytic lesions were found predominantly in the extremities of long bones, bilaterally and symmetrically, spine was spared. Osteosclerosis was present in axial and appendicular skeleton. Pseudo-osteopoikilosis was found symmetrically in epiphyses of femur and humerus, in addition to the pelvis. BMD Z-score greater than +2.5 SD was observed in 13 patients (68.4%). BMD was higher in CGL1 compared to CGL2 in lumbar spine and total body in adults. No associations were found between high BMD and HOMA-IR (p=0.686), DM (p=0.750), osteosclerosis (p=0.127) or pseudo-osteopoikilosis (p=0.342), and, between pain and bone lesions. Fractures were found in 3 patients. Conclusion: Bone manifestations are prevalent, heterogeneous, and silent in CGL1 and CGL2. Osteolytic lesions are the most common, followed by osteosclerosis and pseudo-osteopoikilosis. Bone mass is high in most cases. There was no pain complaint related to bone lesions. Thus, systematic assessment of bone manifestations in CGL is essential. Studies are needed to better understand its pathogenesis and clinical consequences.

Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids (SLIPPERS)-Does it Really Exist?

Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids (SLIPPERS) is a rare variant of the CLIPPERS spectrum with less than ten reports published so far. There is ongoing discussion regarding whether SLIPPERS is a disease entity on its own or just an acronym encompassing many underlying diagnoses, such as sarcoidosis, vasculitis and anti-glial fibrillary acidic protein (GFAP)-associated disease. A 40-year-old woman presented with episodes of language and attention impairment. Magnetic resonance imaging (MRI) revealed T2/FLAIR hyperintense lesions in the subcortical white matter associated with a micronodular, curvilinear perivascular contrast-enhancement. Alternative diagnoses were excluded. There was a remarkable response to steroids. A relapse occurred after six years, and the biopsy showed perivascular T-cell lymphocytic infiltrate, without granulomas, vasculitis, or neoplasia. There was complete resolution of the relapse after steroids. This case represents the longest reported follow-up of a patient diagnosed with SLIPPERS, and brain biopsy after 6 years did not suggest alternative diagnoses. This report contributes to the discussion regarding the possibility that exclusive supratentorial CLIPPERS-like pathology might be an isolated disease entity, but more biopsy-proven cases with a longer follow-up are needed to support this hypothesis. Recently, GFAP astrocytopathy has been characterized and might correspond to a significant number of cases previously diagnosed as CLIPPERS or SLIPPERS.