Leprechaunism

Donohue, W. L.; Uchida, Irene A.

doi:10.1016/s0022-3476(54)80113-2

Cited by 178 publications

(37 citation statements)

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“…5). Ultrastructural examination of the Clusters of clear hepatocytes also have a striking lightmicroscopic resemblance to those of the ''regenerative nodsurrounding hepatic parenchyma showed variable mitochondrial abnormalities, but, in the absence of controlled morpho-ules'' described in some cases of leprechaunism (Donohue's syndrome), 29 but there are significant differences between metric studies, which are beyond the scope of this article, the diagnostic significance of these abnormalities is unclear the two entities. Foci of clear hepatocytes in leprechaunism characteristically cover a large volume of the liver, contain at this time.…”

Section: Methodsmentioning

confidence: 83%

“…In spite of these differences, the presence of focal proliferative bile duct epithelia. 29,30 The clear hepatocellular islands in this entity are typically glycogen-rich and iron-islands of metabolically distinct hepatocytes in these entities is intriguing. depleted in the background of a glycogen-poor and ironloaded liver.…”

Section: Methodsmentioning

confidence: 99%

“…depleted in the background of a glycogen-poor and ironloaded liver. 29,30 Furthermore, the liver is typically depleted Systematic zonation of hepatocellular function across the lobules is a well-known phenomenon, 31 but random metaof fat, both in the foci of clear hepatocytes and in the rest of the parenchyma. 29 Electron-microscopic characteristics of bolic zonation is not a well-explained finding in the liver.…”

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: 83%

Section: Methodsmentioning

confidence: 99%

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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“…In addition to insulin resistance, the former syndrome affects infants with hirsutism, low birth weight, characteristic facial fea tures, and failure to thrive (68,69). Studies of insulin binding to circulating cells have been performed in only one case, and they were normal (70).…”

Section: Clinical States Of Insulin Resistance With Target Cell Defectsmentioning

confidence: 99%

Insulin Receptors and Insulin Resistance

Flier¹

1983

Annu. Rev. Med.

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Resistance to the action of insulin plays a central role in many important disease states, including diabetes and obesity. Many insights into the mecha nism and significance:of insulin resistance in these and other disorders have followed upon our expanding knowledge regarding insulin receptors. In this article, we review our current' understanding of insulin receptors and their regulation, and we assess the role of insulin receptor pathology in the various syndromes characterized by insulin resistance.

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“…Leprechaunism is a rare, inherited disease characterized by an unusual facial appearance, hirsutism, cliteromegaly, and sparse subcutaneous fat stores (1)(2)(3). We have performed detailed metabolic studies on a 2-year-old girl with this syndrome who also presented with acanthosis nigricans and severe insulin resistance.…”

mentioning

confidence: 99%

Insulin resistance due to a defect distal to the insulin receptor: Demonstration in a patient with leprechaunism

Kobayashi¹,

Olefsky²,

Elders³

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

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We have studied a 2-year-old girl with acanthosis nigricans, glucose intolerance, marked hyperinsulinemia, and somatic features characteristic of the leprechaunism syndrome. Circulating plasma insulin levels were increased up to 50-fold and the patient showed a blunted hypoglycemic response to an injection of exogenous insulin (0.2 units/kg), indicating the presence of severe insulin resistance. Insulin purified from the patient's plasma was normal on the basis of chromatographic, electrophoretic, and immunologic criteria. Furthermore, the purified insulin competed effectively with 125I-labeled insulin for binding to insulin receptors on cultured IM-9 lymphocytes and rat fat cells and also exhibited normal biological potency when tested on rat fat cells. Anti-insulin receptor and anti-insulin antibodies were not detected in the patient's plasma, and plasma levels of glucagon, growth hormone, and cortisol were normal. Insulin binding to the patient's circulating mononuclear leukocytes was only slightly depressed into the low normal range and could not account for the severe insulin resistance. Studies on the patient's fibroblasts revealed normal levels of insulin receptors but a total absence of insulin's ability to accelerate glucose transport. Because rates of glucose transport and metabolism were normal in the basal state in the absence of insulin, we conclude that this patient's insulin resistance is due to an inherited cellular defect in the coupling mechanism between occupied insulin receptors and the plasma membrane glucose transport system. Leprechaunism is a rare, inherited disease characterized by an unusual facial appearance, hirsutism, cliteromegaly, and sparse subcutaneous fat stores (1-3). We have performed detailed metabolic studies on a 2-year-old girl with this syndrome who also presented with acanthosis nigricans and severe insulin resistance. Theoretically, insulin resistance can be due to abnormal beta cell secretory products, circulating insulin antagonists, or a cellular defect in insulin action (4). To elucidate the etiology of this patient's insulin resistance, each of these possibilities was examined in detail. Thus, we studied the integrity of her circulating insulin, assayed for potential insulin antagonists, measured cellular insulin receptors, and studied the insulin responsiveness of the patient's cultured fibroblasts in vitro. The results indicate that this patient's insulin resistance is due to a defect in insulin action distal to the insulin receptor. CASE REPORTThe patient, an 18-month-old white girl, had been born after a full-term (41-week gestation) uncomplicated pregnancy and delivery to a gravida I para 1 28-year-old mother who had takenThe costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 3469 no medications during her pregnancy; birth weight was 2600 g. At birth she was noted to have bilateral ingui...

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Leprechaunism

Cited by 178 publications

References 0 publications

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

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

Insulin Receptors and Insulin Resistance

Insulin resistance due to a defect distal to the insulin receptor: Demonstration in a patient with leprechaunism

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