Liver biopsy discloses a new apolipoprotein A-I hereditary amyloidosis in several unrelated Italian families

Obici, Laura; Palladini, Giovanni; Giorgetti, Sofia; Bellotti, Vittorio; Gregorini, Gina; Arbustini, Eloisa; Verga, Laura; Marciano, Sabrina; Donadei, Simona; Perfetti, Vittorio; Calabresi, Laura; Bergonzi, Cesare; Scolari, Francesco; Merlini, Giampaolo

doi:10.1053/j.gastro.2004.03.003

Cited by 71 publications

(57 citation statements)

References 17 publications

(15 reference statements)

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“…These data strengthen and expand previous descriptions of single patients in whom testicular failure was reported in the medical history several years before a diagnosis of cardiac 9 or visceral 11,12 apoA-I amyloidosis was made.…”

Section: Discussionsupporting

confidence: 88%

“…11,12 Compared to other variants this is associated with a mild phenotype due to the slower progression of kidney and liver deposits. The lack of a family history, advanced patient age at renal or hepatic biopsy and the limited evidence of disease related mortality strengthen this view.…”

Section: Discussionmentioning

confidence: 99%

“…Screening for apoA-I mutations was done by direct sequencing of polymerase chain reaction amplified fragments, as previously described. 11 …”

Section: Methodsmentioning

confidence: 99%

“…We recently referred to an amyloidogenic variant of apoA-I associated with a predominantly sporadic presentation, in which the leucine residue at position 75 is replaced by proline (Leu75Pro). 11 In the first 2 series of patients in whom the diagnosis was confirmed by genetic and immunohistochemical analyses surgically treated Gyn was reported in a few, 11,12 suggesting testicular localization of the disease. However, no additional studies were performed in these subjects.…”

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confidence: 99%

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Infertility and Hypergonadotropic Hypogonadism as First Evidence of Hereditary Apolipoprotein A-I Amyloidosis

et al. 2007

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Purpose:We report that primary infertility and hypergonadotropic hypogonadism in young patients may be caused by testicular amyloidosis and it is associated with the presence of a mutation in the apoA-I gene, resulting in the replacement of proline for leucine at residue 75 of the protein. Materials and Methods:Ten patients presenting with infertility, gynecomastia, decreased libido, erectile dysfunction or a family history of amyloidosis underwent clinical evaluation, hormone assays, semen analysis, ultrasonographic investigation of the testicles, testicular biopsy and DNA sequencing of the apoA-I gene. Results: All patients showed azoospermia and 9 had increased testicular volume. Massive amyloid deposition was observed in all testicular biopsies and the apoA-I mutation of replacement of proline for leucine at residue 75 of the protein was noted. Five patients showed hypergonadotropic hypogonadism and 5 had normal testosterone values with high gonadotropin levels. Conclusions: Nonobstructive azoospermia and macro-orchidism with or without hypogonadism may be caused by hereditary apoA-I amyloidosis in young patients. Testicular amyloidosis can be the first manifestation of this systemic disease. Specific staining for amyloid deposits and genetic analysis of apoA-I mutations are recommended in young, infertile patients with macro-orchidism. Finally, surveillance in asymptomatic mutation carriers is suggested to evaluate the opportunity to implement sperm retrieval and start androgen replacement therapy when necessary.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

“…Screening for apoA-I mutations was done by direct sequencing of polymerase chain reaction amplified fragments, as previously described. 11 …”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Infertility and Hypergonadotropic Hypogonadism as First Evidence of Hereditary Apolipoprotein A-I Amyloidosis

et al. 2007

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“…105200) was coined by Ostertag 1 in 1932 following the discovery of two families with dominantly inherited renal amyloidosis. Mutations in the genes encoding apolipoprotein A-I (apoAI), [2][3][4][5][6][7][8][9][10][11][12] apolipoprotein A-II (apoAII), 13 fibrinogen A␣-chain, 14 -17 and lysozyme 18 have since been identified as the cause of hereditary renal amyloidosis in different kindreds (Online Mendelian Inheritance of Man no. 105200).…”

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confidence: 99%

Amyloidogenicity and Clinical Phenotype Associated with Five Novel Mutations in Apolipoprotein A-I

Rowczenio

Doğan

Theis

et al. 2011

The American Journal of Pathology

113

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The phenotype of hereditary apolipoprotein A-I amyloidosis is heterogeneous with some patients developing extensive visceral amyloid deposits and end-stage renal failure as young adults and others having only laryngeal and/or skin amyloid, which may be of little clinical consequence. Clinical management and prognosis of patients with systemic amyloidosis depend entirely on correct identification of the fibril protein, such that light chain amyloidosis (AL, previously referred to as "primary"), the most frequently diagnosed type, is treated with chemotherapy, which has absolutely no role in hereditary apolipoprotein A-I amyloidosis. We report five novel apolipoprotein A-I variants, four of which were amyloidogenic and one of which was incidental in a patient with systemic AL amyloidosis. Interestingly, only one of four patients with apolipoprotein A-I amyloidosis had a family history of similar disease. Amyloidosis is a rare disorder characterized by extracellular deposition of fibrillar protein that results in a progressive disruption of structure and function of affected tissues and organs. Amyloidosis is a remarkably heterogeneous disease; it can be acquired or hereditary and systemic or localized.The most common form of systemic amyloidosis is AL (light chain, previously referred to as "primary"), in which the fibrils are derived from monoclonal immunoglobulin light chains and consist of the whole or part of the variable (V L ) domain. The prognosis of systemic AL amyloidosis is generally worse than in other amyloid types, although there is marked heterogeneity in the extent of organ involvement and rate of disease progression. Treatment of AL amyloidosis is with chemotherapy for which there is no role in other amyloid types.Hereditary systemic amyloidosis is a rare autosomal dominant condition caused by deposition of variant proteins as amyloid fibrils. The term "hereditary nonneuropathic systemic amyloidosis" (Online Mendelian Inheritance of Man no. 105200) was coined by Ostertag 1 in 1932 following the discovery of two families with dominantly inherited renal amyloidosis. Mutations in the genes encoding apolipoprotein A-I (apoAI), 2-12 apolipoprotein A-II (apoAII), 13 fibrinogen A␣-chain, 14 -17 and lysozyme 18 have since been identified as the cause of hereditary renal amyloidosis in different kindreds (Online Mendelian Inheritance of Man no. 105200). The clinical amyloidosis syndromes that accompany the various mutations in these different genes are diverse with respect to age at onset, mode of presentation, pattern of organ distribution, rate of progression, and prognosis. Indeed, certain apoAI variants are associated with neuropathy 19,20 such that the nomenclature, which includes the term "nonneuropathic," is confusing and probably no longer appropriate.Supported by the UK Department of Health.Accepted for publication June 15, 2011.The licensed patent rights to perform protein extraction from paraffinembedded tissue for the mass spectrometry-based amyloid typing test were granted by Expression Patholo...

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Apolipoprotein A‐I: the dual face of a protein

2016

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Edited by Barry HalliwellConformational plasticity and flexibility are key structural features of ApoAI in lipid metabolism. Amyloidogenic single point mutations, associated with incurable familial amyloidosis with fibril deposition in peripheral organs, may have a dramatic impact on the structural and functional features of ApoAI. Here, the consistent body of data on ApoAI variants has been reviewed, with the aim of highlighting the hallmarks of the pathology. In accordance with our observations, as well as that of others, we propose a model that accounts for the alteration of the delicate balance between lipid-free/lipid-bound dynamic states which is based on monomer-to-dimer interconversion via domain swapping.

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Liver biopsy discloses a new apolipoprotein A-I hereditary amyloidosis in several unrelated Italian families

Cited by 71 publications

References 17 publications

Infertility and Hypergonadotropic Hypogonadism as First Evidence of Hereditary Apolipoprotein A-I Amyloidosis

Infertility and Hypergonadotropic Hypogonadism as First Evidence of Hereditary Apolipoprotein A-I Amyloidosis

Amyloidogenicity and Clinical Phenotype Associated with Five Novel Mutations in Apolipoprotein A-I

Apolipoprotein A‐I: the dual face of a protein

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