RESUMO
This is a study of a group of 23 patients from 16 families with a shared family tree, developing chronic renal insufficiency (CRI). Out of the 23 patients, 18 were female and five male with an average renal death age of 18.4 years old, showing fevo clinical manifestations. The main reason for consultation was the significant level of anemia. 17 patients had normal arterial tension, 1 patient manifested severe artery hypertension (AHT), 3 manifested mild AHT, and 2 manifested slight AHT. All the patients entered the final stage of CRI with a low level of hemoglobin overaging 6.5 g%. The urinalysis revealed an average SG of 1,010, without proteinuria or with slight proteinuria, lower than 500 mg in 24 hours. Three patients had microhematuria and the remainder had normal urinary sediment. A renal ultrasound in 18 cases revealed a bilateral reduction in the kidney size, loss of the cortcomedullar relation, an increase in the echogenety of the renal parenchyma, scattered in all cases, and the presence of corticomedullar cysts in 5 cases. The histopathological study performed in 8 cases revealed some findings which were compatible with chronic interstitial nephritis with corticomedullar cysts. The findings resemble those described in the literature in cases of familial juvenile nephronophthisis (FJN). An important aspect to be pointed out is the presence of an interstitial infiltrate with mononuclear cells, an even more significant feature than any previously reported. We can conclude that the members of these familial groups are carriers of FJN of recessive autosomic transmission, which, in view of some differences in the clinical presentation, age of onset of, CRI some biochemical and morphological findings, and the absence of genetic alterations as described in type 1 FJN, is a variant of this disease.
Assuntos
Doenças Renais Císticas/genética , Adolescente , Adulto , Criança , Feminino , Humanos , Doenças Renais Císticas/diagnóstico , Masculino , LinhagemRESUMO
Nephronophthisis, an autosomal-recessive cystic kidney disease, is the most frequent monogenic cause for renal failure in childhood. Infantile and juvenile forms of nephronophthisis are known to originate from separate gene loci. We describe here a new disease form, adolescent nephronophthisis, that is clearly distinct by clinical and genetic findings. In a large, 340-member consanguineous Venezuelan kindred, clinical symptoms and renal pathology were evaluated. Onset of terminal renal failure was compared with that in a historical sample of juvenile nephronophthisis. Onset of terminal renal failure in adolescent nephronophthisis occurred significantly later (median age 19 years, quartile borders 16.0 and 25.0 years) than in juvenile nephronophthisis (median age 13.1 years, quartile borders 11.3 and 17.3 years; Wilcoxon test P=.0069). A total-genome scan of linkage analysis was conducted and evaluated by LOD score and total-genome haplotype analyses. A gene locus for adolescent nephronophthisis was localized to a region of homozygosity by descent, on chromosome 3q22, within a critical genetic interval of 2. 4 cM between flanking markers D3S1292 and D3S1238. The maximum LOD score for D3S1273 was 5.90 (maximum recombination fraction.035). This locus is different than that identified for juvenile nephronophthisis. These findings will have implications for diagnosis and genetic counseling in hereditary chronic renal failure and provide the basis for identification of the responsible gene.