Genetic and metabolic liver disease

Rj, Thompson; Portmann, Bernard; Roberts, Eve A.

doi:10.1016/b978-0-7020-3398-8.00004-0

Cited by 9 publications

(3 citation statements)

References 1,258 publications

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“…The small inclusions are irregular and the large inclusions are more spherical and vacuolated. These inclusions typically show positivity by PTAH stain and weak positivity by PAS stain, 19,21 and can be highlighted by immunohistochemistry. Under electron microscopy, these proteinaceous inclusions consisted of densely packed, irregularly arranged tubules of 40 nm in diameter, 19 located in dilated cisternae of the rough endoplasmic reticulum.…”

Section: Discussionmentioning

confidence: 99%

“…The arrangement of the tubules gives rise to the unique and characteristic appearance of a fingerprint. 19,21 It should be noted that rare cases of acquired hepatic fibrinogen storage disease have been reported in the literature. 22,23 For example, Simsek et al described a case that occurred in a 40-year-old woman secondary to estrogen therapy.…”

Section: Discussionmentioning

confidence: 99%

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Hepatic Fibrinogen Storage Disease in a Patient with Hypofibrinogenemia: Report of a Case with a Missense Mutation of the FGA Gene

et al. 2015

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We report a 9-year-old patient with abnormal liver tests found incidentally during routine bloodwork as part of a preoperative evaluation for excision of a benign cyst. A liver biopsy demonstrated hepatocytes to have pale and expanded cytoplasm that contained multiple vague globular eosinophilic inclusions. Electron microscopy showed fingerprint-like structures in the dilated cisternae of the rough endoplasmic reticulum, characteristic of fibrinogen. Whole exome sequencing identified a heterozygous missense mutation at codon 35 of the fibrinogen α (FGA) gene. No mutation was identified in the β or γ chains. His plasma fibrinogen levels were found to be decreased to 85 mg/dL (normal range 215-464). His family history was pertinent for his mother and maternal grandfather with hypofibrinogenemia. He had not had any significant bleeding episodes except for minor bruising over the shins. This case illustrates a rare etiology of storage disease that causes abnormal liver function tests.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hepatic Fibrinogen Storage Disease in a Patient with Hypofibrinogenemia: Report of a Case with a Missense Mutation of the FGA Gene

et al. 2015

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“…Liver histopathology typically reveals microvesicular steatosis (cytoplasmic lipid vesicles stained by Oilred, Sudan black, Sudan IV), lysosomal accumulation of cholesteryl esters, and TG, along with Maltese cross-type birefringent needle-shaped cholesteryl ester crystals in frozen sections. Immunohistochemical use of lysosomal markers in fixed paraffin-embedded samples facilitates the diagnosis of CESD (10,11). Additional biomarker findings that are useful for the diagnosis of LAL-D are high plasma concentration of chitotriosidase as well as elevated oxysterols (12,13).…”

Section: Introductionmentioning

confidence: 99%

A novel variant in the LIPA gene associated with distinct phenotype

Sarajlija

Armengol²,

Maver

et al. 2022

Balkan Journal of Medical Genetics

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Deficiency of lysosomal acid lipase (LAL-D) is caused by biallelic pathogenic variants in the LIPA gene. Spectrum of LAL-D ranges from early onset of hepatosplenomegaly and psychomotor regression (Wolman disease) to a more chronic course (cholesteryl ester storage disease - CESD). The diagnosis is based on lipid and biomarker profiles, specific liver histopathology, enzyme deficiency, and identification of causative genetic variants. Biomarker findings are a useful for diagnostics of LAL-D, including high plasma concentration of chitotriosidase as well as elevated oxysterols. Current treatment options include enzyme replacement therapy (sebelipase-alpha), statins, liver transplantation, and stem cell transplantation. We present two pairs of siblings from Serbia with a distinctive phenotype resembling LAL-D with a novel variant of unknown significance (VUS) detected in the LIPA gene and residual LAL activity. All patients presented with hepatosplenomegaly at early childhood. In siblings from family 1, compound heterozygosity for a pathogenic c.419G>A (p.Trp140Ter) variant and a novel VUS c.851C>T (p.Ser284Phe) was detected. Patients from family 2 were homozygous for c.851C>T VUS and both have typical histopathologic findings for LAL-D in the liver. Enzyme activity of LAL was tested in three patients and reported as sufficient, and therefore enzyme replacement therapy could not be approved. When confronted with a challenge of diagnosing an inherited metabolic disorder, several aspects are taken into consideration: clinical manifestations, specific biomarkers, enzyme assay results, and molecular genetic findings. This report brings cases to light which have a considerable discrepancy between those aspects, namely the preserved LAL enzyme activity in presence of clinical manifestations and rare variants in the LIPA gene.

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Genetic and Metabolic Hepatic Diseases

2017

Pathology of Liver Diseases

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Genetic and metabolic liver disease

Cited by 9 publications

References 1,258 publications

Hepatic Fibrinogen Storage Disease in a Patient with Hypofibrinogenemia: Report of a Case with a Missense Mutation of the FGA Gene

Hepatic Fibrinogen Storage Disease in a Patient with Hypofibrinogenemia: Report of a Case with a Missense Mutation of the FGA Gene

A novel variant in the LIPA gene associated with distinct phenotype

Genetic and Metabolic Hepatic Diseases

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