p.G360R Is a Pathogenic GLA Gene Mutation Responsible for a Classic Phenotype of Fabry Disease

The authors report the case of a classic phenotype of Fabry disease in a 60-year-old male patient presenting with left ventricular hypertrophy and stroke. Genetic analysis revealed 2 GLA-gene variants, i.e., p.R356Q and p.G360R. This clinical case highlights that the finding of 2 or more GLA gene variants in a Fabry patient should lead to a careful evaluation in order to determine their exact role in the condition. This case also provides the first clinical evidence that the p.G360R mutation is pathogenic and responsible for a classic phenotype of Fabry disease. The clinical improvement following the initiation of enzyme replacement therapy reinforces the importance of Fabry disease awareness and diagnosis in patients exhibiting red flags, such as left ventricular hypertrophy and stroke.

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Effect of enzyme replacement therapy on serum asymmetric dimethylarginine levels, coronary flow reserve and left ventricular hypertrophy in patients with Fabry disease

Clinical Kidney Journal ◽

10.1093/ckj/sfs114 ◽

2012 ◽

Vol 5 (6) ◽

pp. 512-518 ◽

Cited By ~ 3

Author(s):

H. Fujii ◽

K. Kono ◽

T. Yamamoto ◽

T. Onishi ◽

S. Goto ◽

...

Keyword(s):

Left Ventricular Hypertrophy ◽

Enzyme Replacement Therapy ◽

Fabry Disease ◽

Replacement Therapy ◽

Coronary Flow ◽

Ventricular Hypertrophy ◽

Asymmetric Dimethylarginine ◽

Left Ventricular ◽

Enzyme Replacement ◽

Flow Reserve

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Fabry Disease

10.1093/med/9780199972135.003.0049 ◽

2016 ◽

Author(s):

Michael West ◽

Gabor Linthorst

Keyword(s):

Natural History ◽

Left Ventricular Hypertrophy ◽

Enzyme Replacement Therapy ◽

Fabry Disease ◽

Patient Outcomes ◽

Ventricular Hypertrophy ◽

Unknown Origin ◽

Left Ventricular ◽

Enzyme Replacement ◽

Modest Effect

Fabry disease was initially believed to be a very rare disorder, but an increase in prevalence following screening studies revealed that it may be more frequent in a less severe (nonclassical) variant. The adult physician can encounter both phenotypes: classical disease arising in childhood, or after establishing the diagnosis in an adult male. The nonclassical phenotype is usually diagnosed after additional investigations in a patient with renal disease or left ventricular hypertrophy (LVH) of unknown origin. Enzyme replacement therapy (ERT) appears to have a modest effect in Fabry disease, and many challenges remain both in understanding the pathophysiology and natural history as well as in improving patient outcomes.

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Mild Left Ventricular Hypertrophy Unravels a Novel Nonsense Mutation of the GLA Gene Associated with the Classical Phenotype of Fabry Disease

Cardiology ◽

10.1159/000455117 ◽

2017 ◽

Vol 137 (2) ◽

pp. 67-73 ◽

Cited By ~ 2

Author(s):

Olga Azevedo ◽

Miguel Gago ◽

Gabriel Miltenberger-Miltenyi ◽

Paulo Gaspar ◽

Nuno Sousa ◽

...

Keyword(s):

Left Ventricular Hypertrophy ◽

Fabry Disease ◽

Nonsense Mutation ◽

Ventricular Hypertrophy ◽

Large Family ◽

Disease Diagnosis ◽

Left Ventricular ◽

The Novel ◽

Complete Evaluation ◽

Gla Gene

We 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.

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