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Plasmatic deacylated globotriaosylceramide (lysoGb3) is elevated in FD patients as a reflection of lysosomal accumulation of Gb3. Specific (AGALopathic)\n                    <jats:italic>GLA<\/jats:italic>\n                    variants have been recently shown to accumulate within the secretory pathway and trigger endoplasmic reticulum stress and unfolded protein response rather than result in profound enzymatic deficiency. In part due to lack of integrative measures of clinical severity and biochemical\/molecular parameters, specific impacts and consequences of X\u2010chromosomal inactivation (XCI) on clinical manifestation in FD female heterozygotes still remain to be fully understood. Our study aimed at evaluation of XCI (% of inactive wt GLA allele) in untreated female FD heterozygotes with classic FD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200917), late\u2010onset FD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200919) and individuals carrying\n                    <jats:italic>GLA<\/jats:italic>\n                    variants (p.(L394P) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097), p.(A143T) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094), and p.(D313Y) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094)) with predominant AGALopathic effects. XCI was correlated with age of the patients, clinical phenotype, (residual) AGAL activity, and lysoGb3. AGAL activity corresponded to XCI independently of the type of the\n                    <jats:italic>GLA<\/jats:italic>\n                    mutation. The best separation of the clinical phenotypes (classic FD, late\u2010onset FD and AGALopathy) was achieved by correlating XCI to the ratio of AGAL activity to lysoGb3. This three parametric calculated marker was then confronted with the Mainz Severity Score Index (MSSI) to generate an Integrative Clinical\u2010Laboratory quotient (ICLq). ICLq discriminated the three female patient groups and demonstrated group\u2010dependent differences in its average age\u2010related increase.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70218","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T07:04:32Z","timestamp":1782111872000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tri\u2010Parametric Assessment of \u03b1\u2010Galactosidase A Activity,\n                    <scp>lysoGb3<\/scp>\n                    and X\u2010Inactivation Aids Genotype\u2010Phenotype Categorization of Fabry Disease Female Patients"],"prefix":"10.1002","volume":"49","author":[{"given":"Ladislav","family":"Kuchar","sequence":"first","affiliation":[{"name":"Research Unit for Rare Diseases, Department of Paediatrics and Inherited Metabolic Disorders First Faculty of Medicine, Charles University and General University Hospital  Prague Czech 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