Lysosomal storage disorders: A review of the musculoskeletal features

James, Rebecca; Singh‐Grewal, Davinder; Lee, Senq J.; McGill, Jim; Adib, Navid

doi:10.1111/jpc.13122

Cited by 20 publications

(20 citation statements)

References 55 publications

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“…Differential diagnoses are numerous and MPS are often misdiagnosed (Table 4). MPS are part of a larger class of diseases, the lysosomal storage diseases that all share common clinical features (32,33). However, MPS are much more often misdiagnosed as rheumatic inflammatory disorders by adult rheumatologists: RA (or JIA if early onset), psoriatic arthritis and sometimes spondylarthritis according to the symptoms.…”

Section: Differential Diagnosesmentioning

confidence: 99%

Mucopolysaccharidoses seen in adults in rheumatology

et al. 2017

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Mucopolysaccharidoses are a group of rare lysosomal storage diseases including a great number of polymorph syndromes, each being related to a particular mutation responsible for a deficiency of glycosaminoglycan degrading enzymes, leading to an accumulation of glycosaminoglycans in tissues. Many of them are diagnosed in children or teenagers and have a severe prognosis because of organ failure, and are consequently usually not seen by the adult rheumatologist. However, some of them have a more progressive presentation, with musculoskeletal symptoms at the forefront and a lifespan that nearly reaches that of the general population. These milder forms are more likely to be diagnosed in adults, in patients who have suffered for years and sometimes even decades with unrecognized mucopolysaccharidosis. Indeed, they can sometimes mimic inflammatory rheumatic disorders, and therefore be misdiagnosed for a long time. Recognition and diagnosis of these attenuated forms can be a real challenge as they lead to moderate and/or nonspecific symptoms such as joint pain or stiffness. Hence, rheumatologists should know about them. Early diagnostic is essential since specific treatment, like enzyme replacement therapy, is now available for some subtypes and might, if given early, slow down the development of tissue damage, which is unfortunately irreversible. This article provides the opportunity to review the main clinical and radiographic features, the diagnostic strategy and the update of management, which should be multidisciplinary and led by an experienced physician in a reference centre. The contribution of the rheumatologist is important to ensure symptom control and prevent complications.

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Section: Differential Diagnosesmentioning

confidence: 99%

Mucopolysaccharidoses seen in adults in rheumatology

et al. 2017

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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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“…Fabry disease (FD) is a rare lysosomal storage disorder caused by mutations of the alpha-galactosidase A gene ( GLA ) which causes premature morbidity due to organ dysfunction following deposition of globotriaosylceramide (Gb3) 1. Presenting symptoms include musculoskeletal pain such as acroparesthesias2 which often result in rheumatological consultations 3. Concerns have been raised that patients with FD are often falsely attributed with classical rheumatological diagnoses, precluding early effective treatment 3…”

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confidence: 99%