Norberto Antongiovanni

Prevalence of chronic kidney disease in fabry disease patients: Multicenter cross sectional study in Argentina

Nephropathy is one of the major complications of Fabry Disease (FD) and mainly includes reduced glomerular filtration rate (GFR) and proteinuria. Despite the frequency, scarce information exists regarding the frequency of CKD as well as other related complications in FD patients in Argentina. The aim of the study was to measure the prevalence of CKD at diagnosis of FD as well as to describe other related conditions in a large cohort of patients with FD. Methods: a cross-sectional study performed in three FD centers of Argentina during January 2014 and January 2016. Information at diagnosis regarding patient demographics, disease characteristics, key laboratory values, and renal, cardiac, cerebrovascular diseases and other related complications were collected. Results: A total of 60 patients were included. The mean age at diagnosis was 25.5 ± 16 years. 42% of included patients presented CKD in which the disease was mild (GFR ≥ 60 and < 90) in 60% (n = 15), moderate (GFR ≥ 30 and < 60) in 16% (n = 4), severe (GFR ≥ 15 and < 30) in 4% (n = 1) and failure (GFR < 15) in 20% (n = 5). Arrhythmias were reported for 13.3% of patients. In 33.3% the echocardiographic evaluation demonstrated left ventricular hypertrophy and peripheral neuropathy in 63.3%. Conclusion: This study presents information regarding the prevalence of CKD in a large cohort of FD patients at the moment of diagnosis in Argentina. Future studies will help us to confirm these initial findings.

Major Organic Involvement in Women with Fabry Disease in Argentina

Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from the deficiency or absence of the alpha galactosidase A enzyme. Organic involvement in men is well known, but in women it is controversial, partly due to the random X-chromosomes inactivation (Lyon hypothesis). The aim of this study was to describe the organic involvement in women at the time of FD diagnosis. A descriptive, cross-sectional and multicenter study was carried out. Thirty-five women with FD from three reference centers in Argentina were evaluated. The mean age of the whole group (n = 35) was 26.6 ± 16.9 years; 22 were adult (over 18) and 13 were paediatric patients. Enzymatic activity was performed in 29/35 patients, which was normal in 24/29 (82.8%). Seven different mutations of the GLA gene were found. The results showed urinary protein loss (45.7%) and decreased glomerular filtration rate (31.4%), mainly in adults. And also, cornea verticillata (56.5%), peripheral neuropathy (51.4%), cardiovascular manifestations (31.4%), hearing loss (20%), angiokeratomas (20%), central nervous system (17.1%), and gastrointestinal involvement (14.3%). Organic compromise in females with FD may be as severe as in men. This analysis has demonstrated a significant proportion of women with signs, symptoms, and major organic involvement at FD diagnosis.

Clinical parameters, LysoGb3, podocyturia, and kidney biopsy in children with Fabry disease: is a correlation possible?

BackgroundFabry disease is an X-linked lysosomal storage disorder caused by α-galactosidase enzyme deficiency. We present clinical, biochemical, and histologic findings in children with classical phenotypic presentation of Fabry disease.MethodsA retrospective analysis was performed using charts from 14 children with confirmed diagnosis. Clinical parameters were evaluated. Globotriaosylsphingosine -lysoGb3- detection in plasma, podocyturia, and kidney biopsy were carried out in all cases.ResultsAll patients except one demonstrated at least one symptom of Fabry disease. LysoGb3 levels were above the normal range in all patients. Podocyturia was documented in all patients. Kidney biopsy revealed glomerular, interstitial, vascular, and tubular changes on light microscopy in nearly all patients. Electron microscopy showed podocyte inclusions in all patients.ConclusionsNo difference in symptomatology was discernible between boys and girls. Podocyturia was detectable in children serving as a possible early marker of kidney injury. LysoGb3 was elevated in all cases, emphasizing the importance for diagnosis especially in female patients with normal αGal A activity. A possible association between lysoGb3 and symptom severity and histological involvement in kidney biopsy should be assessed in prospective studies with enough statistical power to determine if lysoGb3 can be used to predict nephropathy in children with Fabry disease.

Early Renal Involvement in a Girl with Classic Fabry Disease

Fabry disease is an X-linked lysosomal storage disorder resulting from the deficiency or absence of the enzyme alpha galactosidase A; this defect leads to the systemic accumulation of globotriaosylceramide and its metabolites. Organic involvement in men is well known, but in women it is controversial, mainly due to the random X-chromosome inactivation in each of their cells (Lyon hypothesis). This would explain why women (heterozygotes) present a wide variability in the severity of their phenotype. The manifestations are multisystemic and begin in early childhood, reaching a severe compromise in adulthood. Typical acroparesthesia in hands and feet, gastrointestinal symptoms, angiokeratomas, dyshidrosis, hearing loss, arrhythmias, hypertrophic cardiomyopathy, cerebrovascular accidents, and renal failure can be observed. Nephropathy is one of the major complications of Fabry disease. Glomerular and vascular changes are present before progression to overt proteinuria and decreased glomerular filtration rate, even in pediatric patients. A case of incipient renal involvement in a girl with classic Fabry disease is reported.