Recurrent fever of unknown origin: An overlooked symptom of Fabry disease

Fabry disease (FD) is a rare X-linked lysosomal storage disorder due to the absent or deficient activity of lysosomal hydrolase a-galactosidase A (α-Gal A), which leads to the accumulation of its substrates in various organs and tissues. Classic clinical manifestations include angiokeratomas, proteinuria, renal failure, neuropathic pain, and left ventricular hypertrophy. Fever is one of the rare symptoms that may occur during FD.

Three Chinese Han patients with FD referred to Peking Union Medical College Hospital were reported. The complete medical records were established, and detailed data were collected. Whole-exome sequencing by next-generation sequencing and α-Gal A enzyme activity assay were performed to confirm the diagnosis.

These three patients all presented with recurrent fever of unknown origin initially, accompanied with arthralgia/arthritis and other symptoms. We identified two known variants in the GLA gene, c.1176_1179delGAAG and c.782G>A (p.G261D), and a novel variant c.440G>A (p.G147E) which is likely pathogenic in our patient.

FD should be considered as a rare cause of recurrent fever of unknown origin. The coexistence of gene variants related to systemic autoinflammatory diseases may make the clinical phenotypes of FD more complex and prone to recurrent fever.