The impact of fever/hyperthermia in the diagnosis of Fabry: A retrospective analysis

Elena Verrecchia, Anna Zampetti, Daniela Antuzzi, Roberta Ricci, Lorenzo Ferri, Amelia Morrone, Claudio Feliciani, Lorenzo Dagna, Raffaele Manna

Research output: Contribution to journalArticlepeer-review


Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of alpha-galactosidase A enzyme, which leads to the accumulation of its substrate, the globotriaosylceramide or Gb3, in many organs and tissues. Main clinical manifestations of FD are neuropathic pain, angiokeratomas, proteinuria and renal failure, left ventricular hypertrophy and stroke. Fever is also a possible symptom at the onset of the disease during childhood and adolescence, but it is frequently misdiagnosed, causing a delay in FD diagnosis. Methods: We retrospectively analysed the medical records in our series of 58 Fabry patients, focusing on the proportion of patients who exhibited fever as the main symptom at the onset of FD in order to evaluate the diagnostic delay in these patients. Findings: In our series, we found a significant proportion of patients with a history of fevers at the beginning of their medical history (20.7%; 12/58). 83% of patients with fever also exhibited acroparesthesias (10/12). Inflammatory markers were elevated in few of those cases (2/12). The mean diagnostic delay was 15.6. ±. SD 12.8. years. Interpretation: Fever emerged to be common as part of the FD clinical spectrum and it significantly contributed to the diagnostic delay encountered with this rare disease. Furthermore, our retrospective analysis indicated that FD patients commonly exhibit episodes of fever in association with other symptoms suggestive of FD (such as episodic pain crisis, acroparesthesias, hypo/anhydrosis, heat intolerance, fatigue and gastrointestinal distress). A careful analysis of the medical history in patients suffering fever could lead to an early and correct FD diagnosis. We believe that fever/hyperthermia, acroparesthesias and angiokeratoma should be considered for inclusion in the algorithm for Intermittent Fever of Unknown Origin (FUO) in order to improve the recognition of FD.

Original languageEnglish
JournalEuropean Journal of Internal Medicine
Publication statusAccepted/In press - Nov 18 2015


  • Early onset
  • Fabry disease
  • Fever
  • Fever of unknown origin

ASJC Scopus subject areas

  • Internal Medicine


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