Heritable urea cycle enzyme deficiency-liver disease in 16 patients

LaBrecque, Douglas R.; Latham, Patricia S.; Riely, Caroline A.; Hsia, Y. Edward; Klatskin, Gerald

doi:10.1016/s0022-3476(79)80014-1

Cited by 60 publications

(30 citation statements)

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“…Both patients with CPS deficiency and clear hepatocytes had enzyme activity below 10% of expected clear islands in heterozygous (female) patients only. 12 The aggregates of clear hepatocytes in the child with HHH were (patients 1 and 2 histologically indistinguishable from those observed in chil-hepatocytes clearly showed a sharp biochemical contrast to the bulk of the liver parenchyma. PAS staining on frozen dren with CPS or OTC deficiency (Fig.…”

Section: Methodsmentioning

confidence: 81%

“…The periportal nuclear glycogen was prominent with central nuclei'' in five of six heterozygous (female) paand appeared increased in most of the specimens, and occa-tients with OTC deficiency. 12 The hepatocytes in these clussionally led to marked nuclear expansion (Fig. 7).…”

Section: Methodsmentioning

confidence: 96%

“…36,37 In the appropriate clinical setting, Reye syndrome can be confirmed by demonstrating diffuse miincluding one case with portal-to-portal bridging, was noted in six patients with OTC deficiency. 10,12,16 Shapiro et al also crovesicular steatosis and characteristic ultrastructural changes on electron microscopy. 38 The liver biopsy traditiondescribed slight increase in collagen, without specific reference to its lobular distribution.…”

Section: Methodsmentioning

confidence: 99%

“…However, in frozen secThree specimens from 3 children with CPS deficiency, seven tions of formalin-fixed tissue, these aggregates were strongly of fat in the aggregates of clear hepatocytes, and showed lar steatosis with or without accompanying macrovesicular marked expansion of the cytoplasm with glycogen, leading steatosis of the hepatocytes. [5][6][7][10][11][12][13][17][18][19][20][21] The droplets of fat in to the margination of the organelles to the periphery of the these entities can be so small that, occasionally, in spite of cell and around the nucleus (Fig. 5).…”

Section: Methodsmentioning

confidence: 99%

“…A marked creased density of the ground substance'' in the cytoplasm, reticuloendothelial hyperplasia was present in specimens but no speculation was made as to the nature of this cytofrom patients 6 and 8, both of whom were clinically in critical plasmic ground substance. 12 Two years later, Haust et al condition and died of their disease. There was a marked iron described an ill-defined hepatocellular zonation with ''glycodeposition in specimens from patients 5 and 8, both of whom gen-rich'' and ''reticulated'' hepatocytes in a child with had recently received blood transfusions.…”

Section: Methodsmentioning

confidence: 99%

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Focal glycogenosis of the liver in disorders of ureagenesis: Its occurrence and diagnostic significance

Badizadegan

Perez‐Atayde

1997

Hepatology

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action of the urea cycle catalyzed by CPS, ammonia combines Metabolic disorders of ureagenesis can cause a Reye-like with adenosine triphosphate and bicarbonate to form carbasyndrome with potentially fatal hyperammonemia in children. myl phosphate. Carbamyl phosphate then reacts with orni-A mechanistically heterogeneous subset of these disorders thine to form citrulline in the first step of the actual urea shares the biochemical end-result of impaired mitochondrial synthesis in a reaction catalyzed by OTC. A deficiency in citrulline production. These include deficiencies of the mitoeither of these two enzymes will directly reduce mitochonchondrial enzymes, ornithine transcarbamylase (OTC) and drial citrulline production, and lead to impaired urea synthecarbamyl-phosphate synthase (CPS), as well as dibasic aminosis (Fig. 1). In contrast, impaired urea synthesis in dibasic acidurias hyperammonemia-hyperornithinemia-homocitrulaminoacidurias is the result of a functional deficiency in linuria (HHH) and lysinuric protein intolerance (LPI). In this citrulline production because of reduced mitochondrial ornireport, we present histopathology of the liver in 10 children thine levels. In hyperammonemia-hyperornithinemia-homowith defects of ureagenesis, including 6 with OTC deficiency, citrullinuria (HHH), the presumed defect is in the transport 3 with CPS deficiency, and 1 with HHH. The liver showed of cytoplasmic ornithine across the mitochondrial memdiffuse microvesicular steatosis, marked periportal nuclear branes ( Fig. 1). In lysinuric protein intolerance (LPI), the glycogen, and variable portal fibrosis with occasional delicate presumed defect is in the intestinal, hepatic, and renal transportal-to-portal bridging. Discrete aggregates of distended heport of ornithine and other dibasic amino acids. The defective patocytes with central nuclei and nonvacuolated clear cytointestinal absorption and reduced renal tubular reabsorption plasm were present in 5 of the 10 children, including two 2 of ornithine are thought to result in decreased plasma orni-OTC deficiency, 2 with CPS deficiency, and 1 with HHH.thine levels, which, in combination, with reduced hepatic Similar aggregates had been previously noted in the liver of some children with OTC deficiency or LPI, but their nature uptake, leads to reduced hepatocellular ornithine (Fig. 1). and diagnostic significance had so far remained unknown. Impaired citrulline production by any of the above mechaUsing special stains on frozen tissue sections and electron nisms can interfere with the catabolism of ammonia, causing microscopy, we show that the hepatocytes in these aggregates a Reye-like clinical syndrome with liver dysfunction and sehave little or no cytoplasmic neutral fat, but contain excessive vere, potentially fatal hyperammonemia in infancy or childfree cytoplasmic glycogen, morphologically mimicking a gly-hood. 1 cogen storage disease. In our experience, hepatocellular aggreHistopathology of the liver in CPS and OTC deficiencies gates of this nature do not occur in...

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Section: Methodsmentioning

confidence: 81%

Section: Methodsmentioning

confidence: 96%