Supplementary Material for: Acquired Generalized Lipodystrophy with Extensive Autoimmune Involvement: A Case Report and Review of the Literature

Introduction: Acquired generalized lipodystrophy (AGL) is a rare condition characterized by body fat loss and, usually, metabolic syndrome with or without associated autoimmune diseases. Clinical phenotypes of AGL are heterogenous, making diagnosis and management challenging. Here we present a case of AGL with a unique and dominant autoimmune phenotype that prompts discussion of this rare disorder, the prolonged clinical course, and its optimal management.
Presentation: A two and a half-year-old girl presented with thinning of her arms and legs and vitiligo. She subsequently developed alopecia at age four and Graves’ disease at age twelve with associated Graves’ eye disease. By age fourteen, she developed Addison’s disease and typical features of severe AGL with fat loss from the extremities and buttocks, venomegaly, muscle hypertrophy, and acanthosis nigricans. She had mild dyslipidemia but normal fasting insulin, HbA1c, and leptin levels. Although her parents were consanguineous, next-generation sequencing of a targeted but comprehensive lipodystrophy gene panel was negative. The negative genetics, clinical features, and presence of autoimmune diseases favored a diagnosis of AGL.
Conclusion: This case is unusual in that (i) it was associated with several autoimmune diseases (Graves’ disease, Addison’s disease, vitiligo, and alopecia); (ii) leptin levels were normal despite lipodystrophy; (iii) her Graves’ disease was associated with severe eye disease. Given the distinct but unusual phenotype (multiple autoimmune diseases associated with generalized lipodystrophy in the absence of hypoleptinemia) and parental consanguinity, despite negative targeted gene sequencing, our patient’s AGL may have been due to a novel, autosomal recessive genetic variant. Whole-genome sequencing would be useful in this case to try to determine a genetic cause to provide new insights into AGL and the underlying autoimmune mechanisms.