Partial Lipodystrophy Affecting the Extremities in a Young Woman With Autoimmune Polyglandular Syndrome 1

Area of Science:

• Endocrinology
• Genetics
• Immunology

Background:

• Autoimmune Polyglandular Syndrome 1 (APS1) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene.
• It typically presents with chronic mucocutaneous candidiasis, primary hypoparathyroidism, and adrenal insufficiency.

Observation:

• A 39-year-old woman with a confirmed diagnosis of APS1 developed partial lipodystrophy in adulthood.
• She experienced symptoms of APS1 since infancy, including candidiasis and hypoparathyroidism, followed by hypothyroidism, adrenal, and ovarian insufficiency in childhood.
• The patient underwent a bone marrow transplant at age 14 for refractory fungal infections and later presented with severe hypertriglyceridemia and significant loss of subcutaneous fat.

Findings:

• Whole-exome sequencing identified biallelic pathogenic variants (p.Leu28Pro and p.Arg257*) in the AIRE gene.
• Autoantibodies against MAGEB1, MAGEB4, and RFX6 were detected, consistent with APS1.
• No known lipodystrophy gene variants were found, suggesting a novel mechanism for lipodystrophy in this patient.

Implications:

• This case suggests a potential link between APS1 and partial lipodystrophy, possibly mediated by autoantibodies targeting adipocyte-expressed proteins.
• Further research is needed to confirm the causal relationship between autoantibodies against specific adipose tissue-expressed proteins (ODC1, NUCKS1, FNBP1L) and the development of lipodystrophy in APS1 patients.