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A Fabry disease (FD) (OMIM 301500) is a genetical disorder X-linked that results from a deficiency of the lysosomal enzyme alpha-galactosidase. It leads to accumulation of its substrate globotriaosylceramide (GL3) and globotriaosylsphingosine (LysoGb3), mainly in heart, endothelial and renal cell. Two major phenotypes, classic and later-onset, have been identified. The classic phenotype is caused by absent or minimal (<3% of mean normal) residual alfa-galactosidase activity. The natural history of patient with Fabry disease studies showed that complications occurred at a mean age of approximately 40 years old.
Describe the clinical characteristics and provide information on the genotype-phenotype of one adult patient of 40 years with Fabry disease who have a novel variant, without typical renal failure.
A 40-year-old man with hearing loss was an dermatology appoint, for naevus-like lesions. He had angiokeratomas predominatly in genitals and inguinals areas. The onset of symtomps occurs during childhood with abdominal and neuropathic pain crisis. Suspected FD was confirmed by low Alpha Galactosidase and high Lyso – GL-3, and genetic testing that showed pathogenic hemizygous variant in GLA, NM_000169:c.856dup p.(Leu286ProfsTer13) classified as likely pathogenic. Its corresponds to the duplication G, generating a change in the reading frame and the appearance of a premature stop codon 13 amino acids downstream in the resulting protein, which through the mechanism of NMD (Nonsense Mediated Decay) would result in the loss of protein function. Basal Echocardiogram and cardiac Magnetic resonance (RMN) showed left ventricular hypertrophy (LVH). The laboratory showed decline renal function and mild proteinuria. He was started treatment with beta agalactosidase.
Patients with FD are identified in screening studies of individuals with stroke, renal failure, or cardiomyopathy. However it is important to know natural history of the disease but do not forget less frequent organic compromises such as hearing loss. The identification of this unique genetic variant not only contributes to our understanding of Fabry disease but also raises questions about the true diversity in its clinical presentations.