A classical phenotype of Anderson-Fabry diseasein a female patient with intronic mutations of the GLA gene: a case report

Riccardo Alessandro, Carmela Zizzo, Giuseppe Albeggiani, Antonio Pisani, Paolo Colomba, Francesco Iemolo, Giovanni Duro, Massimo Imbriaco, Carmela Zizzo, Paolo Colomba

Risultato della ricerca: Article

12 Citazioni (Scopus)

Abstract

Background: Fabry disease (FD) is a hereditary metabolic disorder caused by the partial or total inactivationof 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 screeninginitiatives 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.Case presentation: 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 lamellarinclusions 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.
Lingua originaleEnglish
pagine (da-a)39-44
Numero di pagine6
RivistaBMC Cardiovascular Disorders
Volume12
Stato di pubblicazionePublished - 2012

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Galactosidases
Fabry Disease
Phenotype
Mutation
Genes
Newborn Infant
Podocytes
Glycosphingolipids
Mesangial Cells
Nucleic Acid Regulatory Sequences
Transient Ischemic Attack
Left Ventricular Hypertrophy
Hydrolases
Lysosomes
Taiwan
Chronic Renal Insufficiency
Italy
Hand
Hot Temperature
Kidney

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cita questo

A classical phenotype of Anderson-Fabry diseasein a female patient with intronic mutations of the GLA gene: a case report. / Alessandro, Riccardo; Zizzo, Carmela; Albeggiani, Giuseppe; Pisani, Antonio; Colomba, Paolo; Iemolo, Francesco; Duro, Giovanni; Imbriaco, Massimo; Zizzo, Carmela; Colomba, Paolo.

In: BMC Cardiovascular Disorders, Vol. 12, 2012, pag. 39-44.

Risultato della ricerca: Article

Alessandro, R, Zizzo, C, Albeggiani, G, Pisani, A, Colomba, P, Iemolo, F, Duro, G, Imbriaco, M, Zizzo, C & Colomba, P 2012, 'A classical phenotype of Anderson-Fabry diseasein a female patient with intronic mutations of the GLA gene: a case report', BMC Cardiovascular Disorders, vol. 12, pagg. 39-44.
Alessandro, Riccardo ; Zizzo, Carmela ; Albeggiani, Giuseppe ; Pisani, Antonio ; Colomba, Paolo ; Iemolo, Francesco ; Duro, Giovanni ; Imbriaco, Massimo ; Zizzo, Carmela ; Colomba, Paolo. / A classical phenotype of Anderson-Fabry diseasein a female patient with intronic mutations of the GLA gene: a case report. In: BMC Cardiovascular Disorders. 2012 ; Vol. 12. pagg. 39-44.
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abstract = "Background: Fabry disease (FD) is a hereditary metabolic disorder caused by the partial or total inactivationof 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 screeninginitiatives 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.Case presentation: 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 lamellarinclusions 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.",
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T1 - A classical phenotype of Anderson-Fabry diseasein a female patient with intronic mutations of the GLA gene: a case report

AU - Alessandro, Riccardo

AU - Zizzo, Carmela

AU - Albeggiani, Giuseppe

AU - Pisani, Antonio

AU - Colomba, Paolo

AU - Iemolo, Francesco

AU - Duro, Giovanni

AU - Imbriaco, Massimo

AU - Zizzo, Carmela

AU - Colomba, Paolo

PY - 2012

Y1 - 2012

N2 - Background: Fabry disease (FD) is a hereditary metabolic disorder caused by the partial or total inactivationof 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 screeninginitiatives 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.Case presentation: 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 lamellarinclusions 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.

AB - Background: Fabry disease (FD) is a hereditary metabolic disorder caused by the partial or total inactivationof 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 screeninginitiatives 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.Case presentation: 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 lamellarinclusions 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.

KW - Anderson-Fabry

KW - mutation

UR - http://hdl.handle.net/10447/75407

M3 - Article

VL - 12

SP - 39

EP - 44

JO - BMC Cardiovascular Disorders

JF - BMC Cardiovascular Disorders

SN - 1471-2261

ER -