Fabry disease ‘The New Great Imposter’: results of the French Observatoire in Internal Medicine Departments (FIMeD)

Abstract

Fabry disease (FD) is an X-linked lysosomal storage disorder due to α-galactosidase A deficiency. It is associated with a broad range of clinical symptoms, resulting in frequent misdiagnosis and diagnostic delay, which may impact on patient outcomes. This retrospective observational study of 58 FD patients referred to 10 internal medicine departments in France aimed to review differential diagnoses received prior to diagnosis and examines diagnostic delay. The average age at the time of diagnosis was 27.6 years (range: 10-60) and 42.2 years (range: 9-77) among the 23 males and 35 females analyzed, respectively. Most common symptoms that led to FD diagnosis were family history of FD (12 males and 27 females), followed by pain in extremities (10 males and 5 females), and angiokeratoma (8 males and 4 females). Eighteen patients had received alternative diagnoses prior to FD diagnosis, including a female patient with four previous diagnoses. Four case reports are presented, which illustrate the diagnostic 'odyssey' and delayed diagnosis often experienced by patients. Clinicians should consider a diagnosis of FD when presented with a wide range of symptoms, thus helping to shorten the diagnostic delay and facilitating early therapy with enzyme replacement therapy to improve patient outcomes.

Disease Progression Modeling to Evaluate the Effects of Enzyme Replacement Therapy on Kidney Function in Adult Patients with the Classic Phenotype of Fabry Disease

“…This is an “old” FD population where a great proportion of the patients had advanced kidney disease, when ERT was initiated and offered to all FD patients in 2001. Additionally, as FD is rare, patients experience a delayed diagnosis also resulting in treatment delay [34]. In agreement with our results, a significant loss of renal function over time has repeatedly been demonstrated in patients with FD even under ERT.…”

Fabry disease in infancy and early childhood: a systematic literature review

“…In the cold, patients may complain of increased pain or numbness in the extremities. 15,33,34 In the under 5-year-old age group, there are reports of three children affected by heat and cold intolerance at ages 3.5, 4.0, and 4.4 years. In all three of the reported cases, temperature sensitivity was associated with hypohidrosis or decreased sweating.…”

Phenotype and Genotype Characterization and Twin Association in Patients with Anderson-Fabry Cardiomyopathy

“…However, this progressive multipleorgan disease results in frequent misdiagnosis and diagnostic delay, which may impact patient outcomes [1] .…”

“…FD is associated with a broad range of clinical symptoms, including: pain and paresthesias in the extremities; sensorineural hearing loss; angiokeratoma; corneal and lenticular opacities; hypohidrosis; gastrointestinal, cardiac, and renal dysfunction, and transient ischemic attack/stroke [1] . The typical features of Fabry's cardiomyopathy have been investigated in recent years; the early stage is characterized by left ventricular (LV) hypertrophy and reduced regional myocardial function [4] .…”

“…Once a diagnosis is made, FD can be effectively and safely treated with enzyme replacement therapy (ERT) [1] , available since 2001, allowing a variety of clinical benefits, including improved renal pathology/function and cardiac function [3] . However, this progressive multipleorgan disease results in frequent misdiagnosis and diagnostic delay, which may impact patient outcomes [1] .…”