RÉSUMÉ
Introduction: Fabry disease is a x-chromosome hereditary disease with an incidence of 1/40000 newborns. Nowadays it presents as much in males as in females and its first clinical symptoms are seen in pediatric patients. Patients have reduced or no activity of alpha-galactosidase which leads to progressive accumulation of GL-3 in lysosomes of all types of cells. This early deposition disrupts lysosomal function, leading to cell death, metabolic problems, vascular lesions, endothelial dysfunction, oxidative stress, alterations in autophagy tissue ischemia, and finally producing fibrosis in different tissues. On the other hand, ureteropelvic junction obstruction (UPJO) is the most frequent congenital anomaly of the urinary tract; with an incidence of 1 in 1000-2000 newborns. A patient with antenatal diagnosis of Fabry disease and pre-natal diagnosis of UPJ is described. GL-3 deposits were found in all progeny of renal cells in the surgical biopsy. Patient Report: Prenatal diagnosis of FD and severe left hydronephrosis (left renal pelvis 23 mm) He was born at term with adequate weight. Enzymatic activity of Alpha-Gal A was low and the molecular analysis confirmed the family’s mutation. Pyeloplasty was performed when he was 17 months old and, having obtained informed consent, a small piece of kidney was studied, showing evidence of characteristic GL-3 deposits in all cell types and showed podocyte “effacement”, a marker of injury and stress. Conclusion: We demonstrate in this report that the deposits that lead to the sequence of a series of inflammation and fibrosis are present at a very early age. Based upon this finding, one can speculate about the prevention of late lesions with an early start of enzyme replacement therapy (ERT). Long term follow-up studies will be necessary to confirm this hypothesis.
RÉSUMÉ
Objective To elucidate the clinicopathological and hereditary characteristics in Fabry nephropathy.Methods The clinical and pathological features of 14 patients with Fabry nephropathy were collected.The activities of α-Gal A were measured in 4 probands.Screenings of GLA mutations were done in 12 patients.Results The ratio of Fabry nephropathy in the patients with renal biopsy was 0.074 ％ (14/19 005),the average diagnostic age was (30.57±9.32) years,male to female ratio was 2.5∶ 1.All the patients had proteinuria,and the median of urine total protein (UTP)was 1.71 g/24 h (0.32-4.71 g/24 h).Two of them got nephrotic proteinuria,5 of them got microscopic hematuria,4 of them got renal function insufficiency.Angiokeratomas was the most common manifestation (10/14),followed by cardiac involvement (6/14).Hypohidrosis and diseases of central neural system could also be seen in these patients.There were 9 classic phenotype,the remaining 5 were variants/renal variants.The family information was collected in 10 pedigrees,6 of them had family histories of kidney disease.Renal pathology showed vacuolization of glomerular visceral epithelial cells was the prominent feature,global and segmental glomerulosclerosis were seen in some patients by light microscopy.The myelin bodies or zebra bodies were identified in podocytes by electron microscopy,but only were found in some podocytes of 2 females.The activity of α-Gal A was decreased compared with the normal range in 4 probands.The mutations of GLA were demonstrated in 11 patients.Three novel mutations of GLA gene were identified,which were all deletion/insertion mutations with classic phenotypes.Most variants carried the mutations located in the buried/partial buried areas of α-Gal A (3/11).The classical phenotype carried GLA mutations as W162X,F169S,S201F,N272K,L310R,while variant phenotype carried GLA mutations as I91T,R112H,Q312H.Conclusions The ratio of Fabry nephropathy in patients with renal biopsy is 0.074％.Angiokeratomas and cardiac involvement are often accompanied with Fabry nephropathy.The genotypes of GLA may have close relationships with the phenotypes of Fabry nephopathy.