title: Renal tubular insufficiency, cholestatic jaundice, and multiple congenital anomalies--a new multisystem syndrome.
abstract: We are describing two male siblings with proximal renal tubular insufficiency, cholestatic jaundice, predisposition to infection, and multiple congenital anomalies. These patients presented in the early neonatal period with micrognathia, low set ears, high arched palate, barrel shaped chest, bilateral simian creases, club feet, congenital hip dislocation, hypotonia, conjugated hyperbilirubinemia, repeated infections, and severe failure to thrive. They died at the age of 2 and of 4 months despite medical therapy. Findings of renal tubular insufficiency included persistent renal tubular acidosis, glucosuria, phosphaturia, aminoaciduria, and mild proteinuria. Kidney biopsy, liver biopsy, and a comprehensive immunologic investigation were performed on the first sibling. Kidney histology was normal except for calcification of some distal tubules. Liver biopsy revealed paucity of bile ducts, bile stasis, and some inflammatory cell infiltration. Immunologic investigation suggested a defect in polymorphonuclear cell migration and intracellular killing. Review of the literature revealed remarkably similar findings in two previously reported male siblings. These four cases probably represent a previously unrecognized familial syndrome. The possible etiology and mode of inheritance of this syndrome are discussed, and the association of hepatic and renal tubular dysfunction is reviewed.
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002779:Cholestasis / Q000235:genetics* / Q000473:pathology; D003241:Consanguinity; D006801:Humans; D007231:Infant, Newborn; D007678:Kidney Glomerulus / Q000473:pathology; D008099:Liver / Q000473:pathology; D008297:Male; D015499:Renal Tubular Transport, Inborn Errors / Q000235:genetics* / Q000473:pathology; D013577:Syndrome