Corrigendum to: First case of late onset cardiac phenotype Fabry disease due to an AluYb8 insertion in exon 7 of the GLA gene

Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to deficient α-galactosidase A activity and, consequently, to glycosphingolipid accumulation in a wide variety of cells. Fabry disease due to N215S (c.644A>G, p.Asn215Ser) missense mutation usually results in a late-onset phenotype presenting with isolated cardiac involvement. We herein present the case of a patient with N215S mutation with cardiac involvement, namely left ventricular hypertrophy and ventricular arrhythmias, and end-stage renal disease requiring kidney transplantation. To the best of our knowledge, this is the first report of a kidney-transplanted Fabry patient treated with oral pharmacologic chaperone migalastat.

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Mutations in the GLA Gene and LysoGb3: Is It Really Anderson-Fabry Disease?

International Journal of Molecular Sciences ◽

10.3390/ijms19123726 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3726 ◽

Cited By ~ 22

Author(s):

Giovanni Duro ◽

Carmela Zizzo ◽

Giuseppe Cammarata ◽

Alessandro Burlina ◽

Alberto Burlina ◽

...

Keyword(s):

Fabry Disease ◽

Genetic Variants ◽

Late Onset ◽

Clinical History ◽

Classic Phenotype ◽

Unknown Significance ◽

Male Patients ◽

Alpha Gene ◽

Reliable Marker ◽

Gla Gene

Anderson-Fabry disease (FD) is a rare, progressive, multisystem storage disorder caused by the partial or total deficit of the lysosomal enzyme α-galactosidase A (α-Gal A). It is an X-linked, lysosomal enzymopathy due to mutations in the galactosidase alpha gene (GLA), encoding the α-Gal A. To date, more than 900 mutations in this gene have been described. In our laboratories, the study of genetic and enzymatic alterations related to FD was performed in about 17,000 subjects with a symptomatology referable to this disorder. The accumulation of globotriaosylsphingosine (LysoGb3) was determined in blood of positives. Exonic mutations in the GLA gene were detected in 471 patients (207 Probands and 264 relatives): 71.6% of mutations were associated with the classic phenotype, 19.8% were associated with the late-onset phenotype, and 8.6% of genetic variants were of unknown significance (GVUS). The accumulation of LysoGb3 was found in all male patients with a mutation responsible for classic or late-onset FD. LysoGb3 levels were consistent with the type of mutations and the symptomatology of patients. α-Gal A activity in these patients is absent or dramatically reduced. In recent years, confusion about the pathogenicity of some mutations led to an association between non-causative mutations and FD. Our study shows that the identification of FD patients is possible by associating clinical history, GLA gene analysis, α-Gal A assay, and blood accumulation of LysoGB3. In our experience, LysoGB3 can be considered a reliable marker, which is very useful to confirm the diagnosis of Fabry disease.

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Deficiency in the Screening Process of Fabry Disease: Analysis of Chronic Kidney Patients Not on Dialysis

Frontiers in Medicine ◽

10.3389/fmed.2021.640876 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yuri Battaglia ◽

Fulvio Fiorini ◽

Cristiano Azzini ◽

Pasquale Esposito ◽

Alessandro De vito ◽

...

Keyword(s):

Fabry Disease ◽

Late Onset ◽

Multiple Organ ◽

Lysosomal Storage ◽

Kidney Transplant Recipients ◽

Screening Process ◽

Efficient Treatment ◽

Enzymatic Replacement Therapy ◽

Gla Gene ◽

Disease Analysis

Fabry Disease (FD), a rare and progressive, X-linked lysosomal storage disorder, is caused by mutations in the α-galactosidase A (GLA) gene which leads to enzymatic deficiency of GLA. Misdiagnosed and undiagnosed FD cases are common for the variable FD phenotype, ranging from asymptomatic and/or impairment of single organs, which is typically seen in females and in patients with late-onset mutation, to multiple organ disease, which is frequently found in males with classic GLA mutation. Consequently, for an early diagnosis and an efficient treatment of FD, three different strategies of screening, new-born screening, high-risk screening and familiar screening, have been conducted. However, most of FD screening in the CKD population has been carried out in hemodialysis patients and kidney transplant recipients, for whom the renal damage is already irreversible, so the effectiveness of enzymatic replacement therapy is limited and delayed therapeutic intervention results in worse long-term outcomes. This review investigates the actual strategies of screening initiatives for the identification of FD, examining in detail those performed in CKD patients not on dialysis.

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Myeloid bodies caused by COQ2 mutation: a case with the coincidence of COQ2 nephropathy and IgA nephropathy

Clinical Kidney Journal ◽

10.1093/ckj/sfab043 ◽

2021 ◽

Author(s):

Hai-Feng Ni ◽

Yan Yang ◽

Chun-Qing Li ◽

Tong-Zhou Zhou ◽

Bi-Cheng Liu ◽

...

Keyword(s):

Case Report ◽

Fabry Disease ◽

Iga Nephropathy ◽

Curative Effect ◽

Myeloid Bodies ◽

Cationic Amphiphilic Drugs ◽

First Case ◽

Amphiphilic Drugs ◽

Gla Gene ◽

Coq10 Supplementation

Abstract IgA nephropathy (IgAN) combined with myeloid bodies have been reported in Fabry disease (FD). However, we excluded the diagnosis of FD by no mutation in GLA gene. And she denied the use of cationic amphiphilic drugs. Interestingly, we identified a novel missense mutation for COQ2, which can cause COQ2 mutation associated nephropathy. The patient we reported also had heteromorphic mitochondria, and a good curative effect after CoQ10 supplementation. Combined these, this patient was diagnosed with COQ2 nephropathy and IgAN. To our knowledge, this is the first case report that COQ2 nephropathy with pathologic manifestations of myeloid body in podocytes.

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Left atrial appendage closure device complicated by late-onset pericardial effusion and tamponade: a case report

European Heart Journal - Case Reports ◽

10.1093/ehjcr/ytab058 ◽

2021 ◽

Vol 5 (3) ◽

Author(s):

Stefano Albani ◽

Nicola Berlier ◽

Francesco Pisano ◽

Paolo Scacciatella

Keyword(s):

Pericardial Effusion ◽

Left Atrial ◽

Left Atrial Appendage ◽

Late Onset ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Atrial Appendage ◽

Closure Device ◽

Device Implantation ◽

First Case

Abstract Background Late-onset complications of left atrial appendage occlusion (LAAO) device procedure are anecdotal and there are no such complications reported in literature using Cardia Ultraseal (Cardia, Inc., Eagan, MN, USA). Case summary We report the case of a 74-year-old Caucasian man affected by paroxysmal atrial fibrillation with significant bleeding risk (familiar thrombocytopenia, macroscopic haematuria episodes during therapy with direct oral anticoagulants, HAS-BLED risk score: 4) and ischaemic risk as well (CHADSVASC score: 3). The patient was treated with LAAO device implantation for high bleeding risk. Subsequently, after 26 days from LAAO procedure, he was admitted to the emergency department for haematic cardiac tamponade. The patient was successfully treated with subxyphoidal pericardiocentesis in the acute phase, unfortunately cardiac arrest occurred during the transfer to the referral hospital for urgent cardiac surgery. Permanent neurological damage was reported and the patient died on day 28. Discussion LAAO late-onset complications are very rare and the case presented is the first case described of late-onset pericardial effusion and tamponade secondary to the Cardia Ultraseal LAAO device implantation. We present a revision of the literature regarding the occurrence of similar adverse events and discuss the hypothetical mechanism of this major complication.

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Phenotypic target organ and biomarker variation within a family with late onset Fabry disease

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2020.12.045 ◽

2021 ◽

Vol 132 (2) ◽

pp. S27

Author(s):

Jennifer Coker ◽

Ashlee R. Stiles ◽

Deeksha Bali ◽

Sara P. Young ◽

Marie T. McDonald ◽

...

Keyword(s):

Fabry Disease ◽

Late Onset ◽

Target Organ

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Characterization and phosphoproteomic analysis of a human immortalized podocyte model of Fabry disease generated using CRISPR/Cas9 technology

AJP Renal Physiology ◽

10.1152/ajprenal.00283.2016 ◽

2016 ◽

Vol 311 (5) ◽

pp. F1015-F1024 ◽

Cited By ~ 6

Author(s):

Ester M. Pereira ◽

Anatália Labilloy ◽

Megan L. Eshbach ◽

Ankita Roy ◽

Arohan R. Subramanya ◽

...

Keyword(s):

Fabry Disease ◽

Human Kidney ◽

Premature Death ◽

Antibody Array ◽

Cell Models ◽

Lysosomal Storage ◽

Protein Levels ◽

Gla Gene ◽

Fabry Nephropathy ◽

And Control

Fabry nephropathy is a major cause of morbidity and premature death in patients with Fabry disease (FD), a rare X-linked lysosomal storage disorder. Gb3, the main substrate of α-galactosidase A (α-Gal A), progressively accumulates within cells in a variety of tissues. Establishment of cell models has been useful as a tool for testing hypotheses of disease pathogenesis. We applied CRISPR/Cas9 genome editing technology to the GLA gene to develop human kidney cell models of FD in human immortalized podocytes, which are the main affected renal cell type. Our podocytes lack detectable α-Gal A activity and have increased levels of Gb3. To explore different pathways that could have distinct patterns of activation under conditions of α-gal A deficiency, we used a high-throughput antibody array to perform phosphorylation profiling of CRISPR/Cas9-edited and control podocytes. Changes in both total protein levels and in phosphorylation status per site were observed. Analysis of our candidate proteins suggests that multiple signaling pathways are impaired in FD.

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Hydrocephalus presenting as idiopathic aqueductal stenosis with subsequent development of obstructive tumor: report of 2 cases demonstrating the importance of serial imaging

Journal of Neurosurgery Pediatrics ◽

10.3171/2017.5.peds1779 ◽

2017 ◽

Vol 20 (4) ◽

pp. 329-333 ◽

Cited By ~ 1

Author(s):

Jarod L. Roland ◽

Richard L. Price ◽

Ashwin A. Kamath ◽

S. Hassan Akbari ◽

Eric C. Leuthardt ◽

...

Keyword(s):

Late Onset ◽

Diagnostic Testing ◽

Subsequent Development ◽

Mass Effect ◽

Aqueductal Stenosis ◽

Pineal Region ◽

Serial Imaging ◽

Cerebrospinal Fluid Diversion ◽

First Case

The authors describe 2 cases of triventricular hydrocephalus initially presenting as aqueductal stenosis that subsequently developed tumors of the pineal and tectal region. The first case resembled late-onset idiopathic aqueductal stenosis on serial imaging. Subsequent imaging revealed a new tumor in the pineal region causing mass effect on the midbrain. The second case presented in a more typical pattern of aqueductal stenosis during infancy. On delayed follow-up imaging, an enlarging tectal mass was discovered. In both cases hydrocephalus was successfully treated by cerebrospinal fluid diversion prior to tumor presentation. The differential diagnoses, diagnostic testing, and treatment course for these unusual cases are discussed. The importance of follow-up MRI in cases of idiopathic aqueductal stenosis is emphasized by these exemplar cases.

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