Search Results (3)

Dent disease type 1 is characterized by pathogenic CLCN5 gene variants and impaired receptor-mediated endocytosis in proximal tubules. However, mutation-related abnormalities in proximal tubules have not yet been described. Here, we present three patients with CLCN5 alterations and distinct morphological changes of the apical endocytic-lysosomal apparatus. The proximal tubular ultrastructure was investigated in kidney biopsy samples of three boys genotyped for non-nephrotic proteinuria. Controls: seven patients with nephrotic-range glomerular proteinuria. The genotyping findings revealed an already-known missense mutation in one patient and hitherto undescribed frameshift variants in two patients. Low-molecular-weight proteinuria, focal global glomerulosclerosis, proximal tubular changes, and tubular calcium deposits characterized each case. Three subsets of proximal tubular cells were observed: those without any abnormality, those with aplasia of apical endocytic-lysosomal apparatus and shrinkage of cells, and those with hypoplasia of apical endocytic apparatus, accumulation of proteinaceous substance in dysmorphic lysosomes, and dysmorphic mitochondria. The distribution of subsets varied from patient to patient. In one patient with a frameshift variant, an oxidative stress-like injury of proximal tubular cells and podocytes accompanied the above-mentioned alterations. Focal aplasia/hypoplasia of apical endocytic apparatus and subsequent changes in cytoplasmic organelles characterized proximal tubules in the CLCN5 pathogenic variants. Full article

Background: A high perinatal mortality rate in the Stabyhoun breed prompted one of the Dutch breeding organizations to start an investigation. Preductal segmental tubular aortic hypoplasia is an extremely rarely documented congenital vascular anomaly in dogs, and it is suspected to be the result of constriction of ectopic ductal tissue in the aortic wall at birth. Methods: Over a period of 18 months, Stabyhoun puppies that were stillborn, died or were euthanized before 3 weeks of age were submitted to post-mortem examination at the reporting institution. Pathologic findings were documented. Results: Eight Stabyhoun puppies were submitted during the study period. In five of them, a severe preductal segmental tubular aortic hypoplasia was found. Two of the five puppies were stillborn, and three died spontaneously or were euthanized. Conclusions: Preductal tubular aortic hypoplasia was found in an unusually high frequency in the examined Stabyhoun puppies. Because the condition is believed to cause clinical signs only after birth, this anomaly cannot explain the death of the stillborn puppies. However, it might be responsible for cardiogenic pulmonary edema in the postnatal period. Routine dissection of the great vessels in perinatally deceased puppies would help to establish the prevalence of congenital anomalies of the aorta. Full article

Abnormal aortic arches (AAAs) cover a spectrum of malformations, including abnormal laterality, branching patterns, and flow-limiting narrowing, which themselves vary from tubular hypoplasia, through discrete coarctation, to complete interruption of the arch. Neonatal surgery within the first days of life is necessary for most of these morphologies. Patch aortoplasty is widely used as it can offer a good haemodynamic result, being tailored to each combination of presenting pathologies. Our study hypothesis was that arch malformations are frequent in DORV and exhibit a plethora of phenotypes. We reviewed 54 post-mortem heart specimens from the UCL Cardiac Archive, analysing morphological features that would potentially influence the surgical repair, and taking relevant measurements of surgical importance. AAAs were found in half of the specimens, including 22.2% with aortic arch narrowing. In total, 70% and 30% of narrow arches had a subpulmonary and subaortic interventricular defect, respectively. Z-scores were significantly negative for all cases with tubular hypoplasia. We concluded that arch malformations are a common finding among hearts with DORV. Surgery on the neonatal aortic arch in DORV, performed in conjunction with other interventions that aim to balance pulmonary to systemic flow (Qp/Qs), should be anticipated and form an important part of multi-modal imaging. Full article