{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:46:52Z","timestamp":1787014012082,"version":"build-2736575974"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,9,5]],"date-time":"2014-09-05T00:00:00Z","timestamp":1409875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:p>Fabry disease' (FD) phenotype is heterogeneous: alpha\u2010galactosidase A gene mutations (GLA) can lead to classical or non\u2010classical FD, or no FD. The aim of this study is to describe pitfalls in diagnosing non\u2010classical FD and assess the diagnostic value of plasma globotriaosylsphingosine. This is a case series study. Family 1 (p.A143T) presented with hypertrophic cardiomyopathy (HCM), absent classical FD signs, high residual alpha\u2010galactosidase A activity (AGAL\u2010A) and normal plasma globotriaosylsphingosine. Co\u2010segregating sarcomeric mutations were found. Cardiac biopsy excluded FD. In family 2 (p.P60L), FD was suspected after kidney biopsy in a female with chloroquine use. Males had residual AGAL\u2010A, no classical FD signs and minimally increased plasma globotriaosylsphingosine, indicating that p.P60L is most likely non\u2010pathogenic. Non\u2010specific complications and histology can be explained by chloroquine and alternative causes. Males of two unrelated families (p.R112H) show AGAL\u2010A &lt;5%, but slightly elevated plasma globotriaosylsphingosine (1.2\u20132.0 classical males &gt;50 nmol\/l). Histological evidence suggests a variable penetrance of this mutation. Patients with GLA mutations and non\u2010specific findings such as HCM may have non\u2010classical FD or no FD. Other (genetic) causes of FD\u2010like findings should be excluded, including medication inducing FD\u2010like storage. Plasma globotriaosylsphingosine may serve as a diagnostic tool, but histology of an affected organ is often mandatory.<\/jats:p>","DOI":"10.1111\/cge.12449","type":"journal-article","created":{"date-parts":[[2014,7,7]],"date-time":"2014-07-07T13:23:39Z","timestamp":1404739419000},"page":"161-166","source":"Crossref","is-referenced-by-count":51,"title":["Diagnostic dilemmas in Fabry disease: a case series study on\n                    <scp>GLA<\/scp>\n                    mutations of unknown clinical significance"],"prefix":"10.1111","volume":"88","author":[{"given":"B.E.","family":"Smid","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism Academic Medical Centre of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.E.M.","family":"Hollak","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Academic Medical Centre of Amsterdam  Amsterdam The 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Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.H.","family":"Lekanne Deprez","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Academic Medical Centre of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Timmermans","sequence":"additional","affiliation":[{"name":"Department of Cardiology RadboudUMC  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.E.","family":"Linthorst","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Academic Medical Centre of Amsterdam  Amsterdam The 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