Acrodermatitis Enteropathica, Zinc, and Ultrastructural Lesions in Paneth Cells

Polanco, Iverlis Díaz; Nistal, M.; Guerrero, Jessenia; Vazquez, C.

doi:10.1016/s0140-6736(76)90274-9

Cited by 20 publications

(4 citation statements)

References 11 publications

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“…Some reports have suggested that the inclusion is similar to the cytoplasmic inclusions which are seen in Paneth cells of the bowel in cases of acrodermatitis enteropathica or experimentally induced zinc deficiency [19,24]. However, the fibrillary-like structure of the inclusions did not form a bundle.…”

Section: Discussionmentioning

confidence: 85%

Fibrillary inclusions in neoplastic and fetal acinar cells of the pancreas

Fukayama

Shiozawa

et al. 1996

Vichows Archiv A Pathol Anat

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We report a case of pancreatic acinar cell carcinoma which contained a large number of pleomorphic inclusions with fibrillary internal structures and mature zymogen granules. To clarify the significance of fibrillary inclusions in the differentiation of acinar cells of the pancreas, we further investigated fetal pancreases (gestational weeks 16, 17, 19, 20 and 28). We found two types of inclusions: type A, corresponding to fibrillary inclusion of neoplastic acinar cells, was observed only in a 19-week fetus; type B showed a homogeneous density similar to that of zymogen granules. Type B was observed in all the fetuses after the 17th gestational week. Although the type A inclusion might be generated through a different mechanism than the type B inclusion, the appearance of a large number of fibrillary inclusions in neoplastic acinar cells may represent a transient form of zymogen granule.

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Section: Discussionmentioning

confidence: 85%

Fibrillary inclusions in neoplastic and fetal acinar cells of the pancreas

Fukayama

Shiozawa

et al. 1996

Vichows Archiv A Pathol Anat

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“…This may therefore be an initial event in the progression of AE. Studies of patients with AE, also reported nearly 35 years ago, revealed changes in Paneth cells including the accumulation of abnormal inclusion bodies and giant granules, which were reversed when patients were given oral zinc [40]–[42]. Zinc deficiency or prolonged fasting has been shown to cause the loss of Paneth cell zinc, as measured by reactivity with the zinc chelator dithizone [43] and dithizone injection causes selective killing of Paneth cells [44].…”

Section: Discussionmentioning

confidence: 99%

A Mouse Model of Acrodermatitis Enteropathica: Loss of Intestine Zinc Transporter ZIP4 (Slc39a4) Disrupts the Stem Cell Niche and Intestine Integrity

et al. 2012

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Mutations in the human Zip4 gene cause acrodermatitis enteropathica, a rare, pseudo-dominant, lethal genetic disorder. We created a tamoxifen-inducible, enterocyte-specific knockout of this gene in mice which mimics this human disorder. We found that the enterocyte Zip4 gene in mice is essential throughout life, and loss-of-function of this gene rapidly leads to wasting and death unless mice are nursed or provided excess dietary zinc. An initial effect of the knockout was the reprogramming of Paneth cells, which contribute to the intestinal stem cell niche in the crypts. Labile zinc in Paneth cells was lost, followed by diminished Sox9 (sex determining region Y-box 9) and lysozyme expression, and accumulation of mucin, which is normally found in goblet cells. This was accompanied by dysplasia of the intestinal crypts and significantly diminished small intestine cell division, and attenuated mTOR1 activity in villus enterocytes, indicative of increased catabolic metabolism, and diminished protein synthesis. This was followed by disorganization of the absorptive epithelium. Elemental analyses of small intestine, liver, and pancreas from Zip4-intestine knockout mice revealed that total zinc was dramatically and rapidly decreased in these organs whereas iron, manganese, and copper slowly accumulated to high levels in the liver as the disease progressed. These studies strongly suggest that wasting and lethality in acrodermatitis enteropathica patients reflects the loss-of-function of the intestine zinc transporter ZIP4, which leads to abnormal Paneth cell gene expression, disruption of the intestinal stem cell niche, and diminished function of the intestinal mucosa. These changes, in turn, cause a switch from anabolic to catabolic metabolism and altered homeostasis of several essential metals, which, if untreated by excess dietary zinc, leads to dramatic weight loss and death.

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“…Since the first report by Lombeck et al (1974), several authors (Polanco et al 1976;Bohane et al 1977;Braun et al 1977;Walravens et al 1978) have described abnormal inclusion bodies of Paneth cells in AE. They considered the abnormal inclusion bodies in the Paneth cells as a consistent and characteristic abnormality of this disease.…”

Section: Discussionmentioning

confidence: 99%

“…Since Paneth cells possess a high concentration and a high metabolic rate of zinc (Millar et al 1961), they must be particularly sensitive to zinc deficiency (Koo and Turk 1977). Patients with AE have been known to have low plasma zinc levels (Moynahan and Barnes 1973;Neldner and Hambidge 1975;Polanco et al 1976;Bohane et al 1977;Braun et al 1977;Walravens et al 1978) and depressed serum activity of zinc-dependent enzymes such as alkaline phosphatase (Neldner and Hambidge 1975). Bohane et al (1977) observed that abnormal Paneth cell inclusion bodies in a child with AE disappeared after treatment with zinc sulfate heptahydrate, 150 mg per day, and attributed Paneth cell abnormality to zinc deficiency.…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural alterations of Paneth cells in infants associated with gastrointestinal symptoms.

Kobayashi¹,

Sano

Konno

et al. 1983

Tohoku J. Exp. Med.

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Paneth cells containing abundant and large inclusion bodies found in patients with acrodermatitis enteropathica have been considered as a consistent and characteristic abnormality of this disease. We examined 34 children with gastrointestinal symptoms due to a wide variety of basic diseases and found similar abnormal Paneth cells in most of them, particularly in infants under the age of one year. This abnormality, according to our findings, is attributed to the secondary effect of zinc deficiency due to malnutrition.

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Acrodermatitis Enteropathica, Zinc, and Ultrastructural Lesions in Paneth Cells

Cited by 20 publications

References 11 publications

Fibrillary inclusions in neoplastic and fetal acinar cells of the pancreas

Fibrillary inclusions in neoplastic and fetal acinar cells of the pancreas

A Mouse Model of Acrodermatitis Enteropathica: Loss of Intestine Zinc Transporter ZIP4 (Slc39a4) Disrupts the Stem Cell Niche and Intestine Integrity

Ultrastructural alterations of Paneth cells in infants associated with gastrointestinal symptoms.

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