bromochloroacetic-acid and Metabolism--Inborn-Errors

Publications concerning liver histopathology in fatty liver disease and chronic hepatitis C, iron and copper overload, and liver transplantation from the past year have been surveyed to highlight useful concepts and diagnostic information.. Two microscopic forms of pediatric nonalcoholic steatohepatitis have been described: type 1 in which hepatocyte ballooning and/or pericellular fibrosis accompany the steatosis; and type 2 which has portal tract inflammation and/or fibrosis as the salient accompanying feature. In chronic hepatitis C, the ductular reaction appears to be a major factor associated with fibrosis. In patients transplanted for hepatitis C virus-related cirrhosis, immunostaining of post-transplant liver biopsies for alpha-smooth muscle actin (i.e. in activated hepatic stellate cells) may identify those individuals at risk for severe recurrence. Clinicopathological papers on several forms of non-HFE hemochromatosis were published and Wilson's disease was described in individuals of 60 years or more in age. Cholestasis in childhood was expertly reviewed and histopathologic precursor lesions of hepatocellular carcinoma were also examined in a comprehensive article.. Recent publications with impact on liver biopsy interpretation include a morphologic classification of nonalcoholic steatohepatitis in childhood, the differential diagnosis of childhood cholestasis and pathogenetic factors involved in fibrogenesis in chronic hepatitis C.

Topics: Amyloid; Biliary Tract Diseases; Biopsy; Humans; Iron Overload; Keratins; Liver Diseases; Liver Transplantation; Metabolism, Inborn Errors; Mitochondrial Diseases; Mutation; Peroxisomes

Harlequin icthyosis is a very rare inborn error of epidermal keratinization with autosomal recessive inheritance. Abnormal lipid metabolism in mitochondria with defective lamellar body formation is the main defect leading to hyperkeratosis. Prenatal diagnosis can be done by invasive procedures such as fetal skin biopsy and also by ultrasonography.

Topics: Fatal Outcome; Female; Humans; Ichthyosis, Lamellar; Infant; Keratinocytes; Keratins; Metabolism, Inborn Errors; Skin

Skin biopsies and scale samples from nine infants and one fetus affected with harlequin ichthyosis (HI) were obtained from eight families. Epidermal differentiation was examined by morphologic and biochemical criteria and cell culture studies. Two striking abnormalities were identified; first, keratin and filaggrin expression were abnormal and varied between cases, and, second, in all cases lamellar granules were absent or abnormal, and intercellular lamellae within the stratum corneum were absent. Three HI phenotypes were distinguished by variable expression of epidermal structural proteins. Cases were classified by the absence (type 1) or presence (types 2 and 3) of keratins K6 and K16 ("hyperproliferative" keratins) and by the presence of profilaggrin in the interfollicular epidermis (types 1 and 2 only). Profilaggrin is apparently not converted to filaggrin, but it is retained in the scale. The block in profilaggrin processing may be due to an inactive phosphatase. Siblings in two families (presenting with types 1 and 2) showed the same type classification suggesting that expression of the phenotype is consistent within families but differs between families. Cultured HI keratinocytes were normal by phase microscopy, but abnormal by electron microscopy with no lamellar granules and extensive stacking of the upper layers. We conclude that harlequin ichthyosis is a genetically heterogeneous group of disorders with altered lamellar granules, intercellular lipids, and variation in expression and/or processing of structural protein markers of normal epidermal keratinization. Furthermore, the lamellar granule and structural protein defects may be indirectly related via a mechanism involving phosphorylation/dephosphorylation.

Topics: Biopsy; Cells, Cultured; Cytoplasmic Granules; Fetus; Filaggrin Proteins; Humans; Ichthyosis; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Metabolism, Inborn Errors; Phosphoproteins; Protein Precursors; Proteins; Sweat Glands

Untreated cases of lichen planus have been studied by histochemical techniques. The acid phosphatase reaction in the transitional zone has been quantitatively estimated and compared with the adjacent relatively normal epidermis. It was found that despite a thickened and accentuated granular layer as seen by routine histological methods there was a marked reduction in the intensity of the acid phosphatase reaction. The glucose-6-phosphate dehydrogenase reaction was marked in the upper layers of the epidermis in active lesions of lichen planus. This is similar to psoriasis, but different from normal human epidermis. The suggestion by other authors that lichen planus is an inborn error of metabolism is discussed. The dendritic cells of the epidermis as studied by the ATPase reaction are virtually absent in regions of active lichen planus and the possible significance of this is mentioned. The horny layer gives a dense reaction for phospholipids in lichen planus and this is similar to psoriatic keratin. The significance of this finding is considered.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Dendrites; Glucosephosphate Dehydrogenase; Histocytochemistry; Humans; Keratins; Lichen Planus; Metabolism, Inborn Errors; Naphthols; Phospholipids; Skin