A classical phenotype of Anderson-Fabry disease in a female patient with intronic mutations of the GLA gene: a case report.
BACKGROUND
Fabry disease (FD) is a hereditary metabolic disorder caused by the partial or total inactivation of a lysosomal hydrolase, the enzyme α-galactosidase A (GLA). This inactivation is responsible for the storage of undegraded glycosphingolipids in the lysosomes with subsequent cellular and microvascular dysfunction. The incidence of disease is estimated at 1:40,000 in the general population, although neonatal screening initiatives have found an unexpectedly high prevalence of genetic alterations, up to 1:3,100, in newborns in Italy, and have identified a surprisingly high frequency of newborn males with genetic alterations (about 1:1,500) in Taiwan.


METHODS
We describe the case of a 40-year-old female patient who presented with transient ischemic attack (TIA), discomfort in her hands, intolerance to cold and heat, severe angina and palpitations, chronic kidney disease. Clinical, biochemical and molecular studies were performed.


CONCLUSIONS
Reported symptoms, peculiar findings in a renal biopsy - the evidence of occasional lamellar inclusions in podocytes and mesangial cells - and left ventricular (LV) hypertrophy, which are considered to be specific features of FD, as well as molecular evaluations, suggested the diagnosis of a classical form of FD.We detected four mutations in the GLA gene of the patient: -10C>T (g.1170C>T), c.370-77_-81del (g.7188-7192del5), c.640-16A>G (g.10115A>G), c.1000-22C>T (g.10956C>T). These mutations, located in promoter and intronic regulatory regions, have been observed in several patients with manifestations of FD. In our patient clinical picture showed a multisystemic involvement with early onset of symptoms, thus suggesting that these intronic mutations can be found even in patients with classical form of FD.
Department of Nephrology, University of Naples, Federico II, Italy.
Antonio
A
Pisani
Massimo
M
Imbriaco
Carmela
C
Zizzo
Giuseppe
G
Albeggiani
Paolo
P
Colomba
Riccardo
R
Alessandro
Francesco
F
Iemolo
Giovanni
G
Duro
D000328:Adult; D001706:Biopsy; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000235:genetics; D004252:DNA Mutational Analysis; D018450:Disease Progression; D000795:Fabry Disease / Q000150:complications / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D007674:Kidney Diseases / Q000175:diagnosis / Q000235:genetics; D008279:Magnetic Resonance Imaging; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D000519:alpha-Galactosidase / Q000235:genetics* / Q000378:metabolism
C576330:GLA protein, human; D000519:alpha-Galactosidase