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Ocular signs correlate well with disease severity and genotype in Fabry disease.

Pitz S, Kalkum G, Arash L, Karabul N, Sodi A, Larroque S, Beck M, Gal A - PLoS ONE (2015)

Bottom Line: This finding could be confirmed by applying age adjusted severity scores.Moreover, the prevalence of cornea verticillata was significantly higher in patients with (male, 76.9%; female, 64.5%) and missense (male, 79.2%; female, 67.4%) mutations versus mild missense (male, 17.1%; female, 23.1%) and the p.N215S (male, 15.0%; female, 15.6%) mutations (P<0.01).Further confirmatory studies are needed.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, University Medical Centre, Johannes Gutenberg University, Mainz, Germany.

ABSTRACT
Ocular signs in Fabry disease have generally been regarded to be primarily of diagnostic value. We explored whether ocular findings, alone or in particular in combination with the α-galactosidase A gene mutation, have predictive value for disease severity. Data from the Fabry Outcome Survey (FOS), a large, global database sponsored by Shire, were selected for adult patients who had undergone ophthalmological examination. Three ocular signs were assessed: cornea verticillata, tortuous conjunctival and/or retinal vessels, and cataract. Fabry disease severity was measured using FOS Mainz Severity Score Index and modifications thereof. Ophthalmological data were available for 1203 (699 female, 504 male) adult patients with eye findings characteristic of Fabry disease in 55.1%. Cornea verticillata had a similar distribution in women (51.1%) and men (50.8%), whereas tortuous vessels and Fabry cataract were somewhat more frequent in men than in women. Patients with cornea verticillata, selected as the principal ocular sign for this study, had more severe disease (median score, 20.0) versus those without ocular signs (11.0; P<0.001). This finding could be confirmed by applying age adjusted severity scores. Moreover, the prevalence of cornea verticillata was significantly higher in patients with (male, 76.9%; female, 64.5%) and missense (male, 79.2%; female, 67.4%) mutations versus mild missense (male, 17.1%; female, 23.1%) and the p.N215S (male, 15.0%; female, 15.6%) mutations (P<0.01). Our analyses show a correlation between the prevalence of ocular changes in Fabry disease and disease severity. Consequently, information on ocular findings and α-galactosidase A gene mutation may help assess the risk for more severe Fabry disease. These observed findings are of notable clinical importance, as Fabry disease is characterized by high clinical course variability and only weak genotype-phenotype correlation at the individual patient level. Further confirmatory studies are needed.

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Related in: MedlinePlus

Prevalence of eye findings by type of mutation.Prevalence of eye findings overall (among those patients with mutation information available) and by type of mutation in adult (A) male and (B) female patients.
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pone.0120814.g004: Prevalence of eye findings by type of mutation.Prevalence of eye findings overall (among those patients with mutation information available) and by type of mutation in adult (A) male and (B) female patients.

Mentions: Patients with or missense mutations had a higher prevalence of eye findings compared with patients with mild missense or p.N215S mutations. Among the 836 adult patients with ocular examination and mutation information available, cornea verticillata in particular was notably more frequent in men and women with (76.9% and 64.5%, respectively) or missense mutations (79.2% and 67.4%, respectively) compared with those with mild missense mutations (17.1% and 23.1%, respectively) or the p.N215S mutation (15.0% and 15.6%, respectively; Fig. 4A and B; S6 Table). Similarly, tortuous vessels were more frequent in men with (34.2%) or missense (35.4%) mutations versus men with mild missense mutations (20.0%) or the p.N215S mutation (20.0%; Fig. 4A; S6 Table).


Ocular signs correlate well with disease severity and genotype in Fabry disease.

Pitz S, Kalkum G, Arash L, Karabul N, Sodi A, Larroque S, Beck M, Gal A - PLoS ONE (2015)

Prevalence of eye findings by type of mutation.Prevalence of eye findings overall (among those patients with mutation information available) and by type of mutation in adult (A) male and (B) female patients.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4363518&req=5

pone.0120814.g004: Prevalence of eye findings by type of mutation.Prevalence of eye findings overall (among those patients with mutation information available) and by type of mutation in adult (A) male and (B) female patients.
Mentions: Patients with or missense mutations had a higher prevalence of eye findings compared with patients with mild missense or p.N215S mutations. Among the 836 adult patients with ocular examination and mutation information available, cornea verticillata in particular was notably more frequent in men and women with (76.9% and 64.5%, respectively) or missense mutations (79.2% and 67.4%, respectively) compared with those with mild missense mutations (17.1% and 23.1%, respectively) or the p.N215S mutation (15.0% and 15.6%, respectively; Fig. 4A and B; S6 Table). Similarly, tortuous vessels were more frequent in men with (34.2%) or missense (35.4%) mutations versus men with mild missense mutations (20.0%) or the p.N215S mutation (20.0%; Fig. 4A; S6 Table).

Bottom Line: This finding could be confirmed by applying age adjusted severity scores.Moreover, the prevalence of cornea verticillata was significantly higher in patients with (male, 76.9%; female, 64.5%) and missense (male, 79.2%; female, 67.4%) mutations versus mild missense (male, 17.1%; female, 23.1%) and the p.N215S (male, 15.0%; female, 15.6%) mutations (P<0.01).Further confirmatory studies are needed.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, University Medical Centre, Johannes Gutenberg University, Mainz, Germany.

ABSTRACT
Ocular signs in Fabry disease have generally been regarded to be primarily of diagnostic value. We explored whether ocular findings, alone or in particular in combination with the α-galactosidase A gene mutation, have predictive value for disease severity. Data from the Fabry Outcome Survey (FOS), a large, global database sponsored by Shire, were selected for adult patients who had undergone ophthalmological examination. Three ocular signs were assessed: cornea verticillata, tortuous conjunctival and/or retinal vessels, and cataract. Fabry disease severity was measured using FOS Mainz Severity Score Index and modifications thereof. Ophthalmological data were available for 1203 (699 female, 504 male) adult patients with eye findings characteristic of Fabry disease in 55.1%. Cornea verticillata had a similar distribution in women (51.1%) and men (50.8%), whereas tortuous vessels and Fabry cataract were somewhat more frequent in men than in women. Patients with cornea verticillata, selected as the principal ocular sign for this study, had more severe disease (median score, 20.0) versus those without ocular signs (11.0; P<0.001). This finding could be confirmed by applying age adjusted severity scores. Moreover, the prevalence of cornea verticillata was significantly higher in patients with (male, 76.9%; female, 64.5%) and missense (male, 79.2%; female, 67.4%) mutations versus mild missense (male, 17.1%; female, 23.1%) and the p.N215S (male, 15.0%; female, 15.6%) mutations (P<0.01). Our analyses show a correlation between the prevalence of ocular changes in Fabry disease and disease severity. Consequently, information on ocular findings and α-galactosidase A gene mutation may help assess the risk for more severe Fabry disease. These observed findings are of notable clinical importance, as Fabry disease is characterized by high clinical course variability and only weak genotype-phenotype correlation at the individual patient level. Further confirmatory studies are needed.

Show MeSH
Related in: MedlinePlus