Browsing by Author "Miltenberger-Miltenyi, Gabriel"
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- Mild Left Ventricular Hypertrophy Unravels a Novel Nonsense Mutation of the GLA Gene Associated with the Classical Phenotype of Fabry DiseasePublication . Azevedo, Olga; Gago, Miguel; Miltenberger-Miltenyi, Gabriel; Gaspar, Paulo; Sousa, Nuno; Cunha, DamiãoWe report on the clinical, biochemical, and genetic findings of a large family with the classical phenotype of Fabry disease due to the novel nonsense mutation c.607G>T (p.E203X) of the GLA gene, which occurs in the active site of the α-galactosidase A enzyme. This report highlights that (i) Fabry disease diagnosis should be considered in all cases of unexplained left ventricular hypertrophy (LVH), even in its milder forms; (ii) a complete evaluation of patients with unexplained LVH is important to find diagnostic red flags of treatable causes of LVH, such as Fabry disease; (iii) cascade family screening is paramount to the earlier diagnosis and treatment of other affected family members; and (iv) the Fabry disease phenotype is highly variable in heterozygote females, even within the same family.
- Parkinson’s Disease and Fabry Disease: Clinical, Biochemical and Neuroimaging Analysis of Three PedigreesPublication . Gago, Miguel Fernandes; Azevedo, Olga; Guimarães, Andreia; Teresa Vide, Ana; Lamas, Nuno J.; Oliveira, Tiago Gil; Gaspar, Paulo; Bicho, Estela; Miltenberger-Miltenyi, Gabriel; Ferreira, Joaquim; Sousa, NunoBackground: Sporadic Parkinson's disease (PD) patients have lower α-galactosidase A (α-GAL A) enzymatic activity and Fabry disease (FD) patients potentially carry an increased risk of PD. Objective: Determination of PD prevalence in FD and clinical, biochemical and vascular neuroimaging description of FD pedigrees with concomitant PD. Methods: Clinical screening for PD in 229 FD patients belonging to 31 families, harbouring GLA gene mutation p.F113L, and subsequent pedigree analysis. Gender-stratified comparison of FD+/PD+ patients with their family members with FD but without PD (FD+/PD-) regarding Mainz scores, plasma & leukocytes α-GAL A enzymatic activity, urinary Gb3 and plasma Lyso-Gb3, vascular brain neuroimaging. Results: Prevalence of PD in FD was 1.3% (3/229) (3% in patients aged ≥50 years). Three FD patients, one female (73 years old) (P1) and two males (60 and 65 years old) (P2 and P3), three different pedigrees, presented akinetic-rigid PD, with weak response to levodopa (16% - 36%), and dopaminergic deficiency on 18F-DOPA PET. No pathogenic mutations were found in a PD gene panel. FD+/PD+ patients had worse clinical severity of FD (above upper 75% IQR in Mainz scores), and cortico-subcortical white matter/small vessel lesions. P3 patient was under enzyme therapy, started 1 year before PD diagnosis. P2-P3 patients had higher leucocyte α-GAL A activity (2,2-3 vs.1,0 (median)(nmol/h/mg)). Conclusion: We have shown a high prevalence of PD in a late-onset phenotype of FD, presenting high cerebrovascular burden and weak response to levodopa. Further studies will untangle how much of this PD phenotype is due to Gb3 deposition versus cerebrovascular lesions in the nigro-striatal network.