Musculoskeletal manifestations of Fabry disease: A retrospective study

Lidove, Olivier; Zeller, Valérie; Chicheportiche, Valérie; Meyssonnier, Vanina; Sené, Thomas; Godot, Sophie; Ziza, Jean-Marc

doi:10.1016/j.jbspin.2015.11.001

Cited by 27 publications

(25 citation statements)

References 20 publications

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“…Retrospective studies analysing the medical history of patients with confirmed FD raised concerns that FD may be overlooked in rheumatological practice. In particular, Lidove et al reported that 9 of 40 patients were mistakenly diagnosed with a rheumatic condition in adulthood prior to the diagnosis of FD 3. This is well in line with the data reported by Moiseev et al in their correspondence.…”

supporting

confidence: 78%

“…They observed erroneous rheumatological diagnoses in 28 of 107 confirmed FD cases across all age groups. Of importance, a significant delay of FD diagnosis from first symptoms is often reported 3–5. For instance, Lidove et al report a mean age at diagnosis of 37.2 years with a range up to 71 years in their study focusing on musculoskeletal complaints of FD patients 3.…”

mentioning

confidence: 99%

“…Of importance, a significant delay of FD diagnosis from first symptoms is often reported 3–5. For instance, Lidove et al report a mean age at diagnosis of 37.2 years with a range up to 71 years in their study focusing on musculoskeletal complaints of FD patients 3. Moreover, a cross-sectional study from the Fabry Outcome Survey comparing older (>50 years) to younger patients with confirmed FD showed that the mean age at first diagnosis was >50 years in the older FD patients, representing 34% of the 1934 patients included 6.…”

mentioning

confidence: 99%

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Response to ‘What rheumatologist should know about Fabry disease’ by Moiseevet al

Vordenbäumen

Brinks

Albrecht³

et al. 2019

Ann Rheum Dis

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supporting

confidence: 78%

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confidence: 99%

mentioning

confidence: 99%

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Response to ‘What rheumatologist should know about Fabry disease’ by Moiseevet al

Vordenbäumen

Brinks

Albrecht³

et al. 2019

Ann Rheum Dis

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“…The main musculoskeletal symptoms described in early FD is acroparesthesia. However, chronic in ammatory joint and bone diseases (polyarticular, oligo and monoarticular, gout, osteoporosis), degenerative joint conditions, neurologic arthropathy (Charcot's foot) (7), Heberden-like nodules (24) and also myositis have been described (8). Nowadays, the coexistence of FD and autoimmune disease has gained increased visibility in the medical literature, and patients with FD and systemic lupus erythematosus (25,26) rheumatoid arthritis (27), autoimmune hypothyroidism (28), Ig A nephropathy (29) and granulomatosis with polyangiitis (30) have also been described.…”

Section: Discussionmentioning

confidence: 99%

Frequency of Fabry disease in a Juvenile Idiopathic Arthritis Cohort

Paim-Marques

Cavalcante

Verçosa

et al. 2020

Preprint

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Background: Fabry disease (FD) is a rare, X-linked, multisystemic lysosomal storage disorder (LSD) that results from a deficiency in the hydrolase alpha-galactosidase A (⍺-GalA). During childhood, classic FD symptomatology is rare. The majority of children may show non-specific symptoms, including in the musculoskeletal system. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients is unknown. Objective: The aim of this study was to identify the frequency of FD in a JIA cohort, characterizing early clinical symptoms, enzyme titers and GLA genotyping. Methods: Children with JIA followed in a tertiary Children Hospital cohort were selected. Clinical, laboratorial, and familiar information were recorded. Molecular genetic testing to detect GLA gene mutations was performed in girls and enzymatic analysis in boys. Results: In 89 patients (56.2% female, age at disease onset: 8.93 ± 4.35 years), one male (1.12%) patient presented pathogenic mutation in GLA gene, c.1244T>C p.L415P, one female patient had a variant of uncertain significance c.38C>T (p.Ala13Val). The enzymatic activity of alpha galactosidase was slightly decreased in 3 additional (3.4%) patients. We observed the presence of intronic variants in 44.44% patients in our cohort: c.1000-22C> T; c.370-81_-77del; c.640-16A> G; c.10C>T; c.548-125C> G and c.-12G> A. These variants and their combination were associated with clinical symptoms in our cohort.Conclusions: The incidence of FD in our cohort was 1.12%. Intronic variants were associated with symptoms previously described in literature. Screening for FD in JIA may be a reasonable strategy for those with atypical pattern of pain.

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“…FD patients are commonly misdiagnosed [3,4]. Incorrect diagnoses are often related to rheumatologic conditions, since patients may present with different rheumatic and immune-mediated manifestations [5][6][7][8][9][10][11][12][13]. Inappropriate diagnosis may lead to improper therapies and delay in FD recognition and adequate treatment initiation, thus hampering prognosis.…”

Section: Introductionmentioning

confidence: 99%

Higher rate of rheumatic manifestations and delay in diagnosis in Brazilian Fabry disease patients

Neto¹,

Bento²,

Pereira³

2020

Adv Rheumatol

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Background: Fabry disease (FD) is an X-linked lysosomal disorder due to mutations in the GLA gene resulting in defective enzyme alpha-galactosidase A. FD patients are frequently misdiagnosed, commonly for rheumatic diseases. Determining pathogenicity of a mutation depends of in silico predictions but mostly on available clinical information and interpretation may change in light of evolving knowledge. Similar signs and symptoms in carriers of GLA gene genetic variants of unknown significance or of benign variants may hamper diagnosis. This study reviews rheumatic and immune-mediated manifestations in a cohort of Brazilian FD patients with classic mutations and also in subjects with GLA gene A143T and R118C mutations. Misdiagnoses, time to correct diagnosis or determination of GLA gene status, time to treatment initiation and reasons for treatment prescription in A143T and R118C subjects are reviewed. Methods: Genotype confirmed classic FD patients (n = 37) and subjects with GLA gene mutations A143T and R118C (n = 19) were referred for assessment. Subjects with R118C and A143T mutations had been previously identified during screening procedures at hemodialysis units. All patients were interviewed and examined by a rheumatologist with previous knowledge of disease and/or mutation status. A structured tool developed by the authors was used to cover all aspects of FD and of common rheumatic conditions. All available laboratory and imaging data were reviewed. Results: Thirty-seven consecutive FD patients were interviewed-16 male / 21 female (mean age: 43.1 years) and 19 consecutive subjects with GLA gene mutations R118C and A143T were evaluated-8 male / 11 female (mean age: 39.6 years); 15 [R118C] / 4 [A143T]. Misdiagnosis in FD patients occurred in 11 males (68.8%) and 13 females (61.9%) of which 10 males and 9 females were previously diagnosed with one or more rheumatic conditions, most frequently rheumatic fever or "rheumatism" (unspecified rheumatic disorder). Median time for diagnosis after symptom onset was 16 years (range, 0-52 years). Twenty-two patients were treated with enzyme replacement therapy (ERT)-13 male and 9 female. Median time to ERT initiation after FD diagnosis was 0.5 years (range, 0-15 years). Rheumatic manifestations occurred in 68.4% of R118C and A143T subjects. Two subjects had been prescribed ERT because of renal disease [R118C] and neuropsychiatric symptoms [A143T]. Conclusion: Misdiagnoses occurred in 64.8% of FD patients, most frequently for rheumatic conditions. Median time for correct diagnosis was 16 years. Rheumatic manifestations are also frequent in subjects with GLA gene R118C and A143T mutations. These results reinforce the need to raise awareness and increase knowledge about Fabry disease among physicians, notably rheumatologists, who definitely have a role in identifying patients and determining disease burden. Decision to start treatment should consider expert opinion and follow local guidelines.

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Musculoskeletal manifestations of Fabry disease: A retrospective study

Cited by 27 publications

References 20 publications

Response to ‘What rheumatologist should know about Fabry disease’ by Moiseevet al

Response to ‘What rheumatologist should know about Fabry disease’ by Moiseevet al

Frequency of Fabry disease in a Juvenile Idiopathic Arthritis Cohort

Higher rate of rheumatic manifestations and delay in diagnosis in Brazilian Fabry disease patients

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