Τίτλος:
A new genetic variant of hereditary apolipoprotein A-I amyloidosis: a case-report followed by discussion of diagnostic challenges and therapeutic options
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background: Hereditary amyloidosis refers to a wide spectrum of rare diseases with different causative mutations in the genes of various proteins including transthyretin, apolipoprotein AI and AII, gelsolin, lysozyme, cystatin C, fibrinogen Aα-chain, β2-microglobulin, apolipoprotein CII and CIII. Case presentation: Among hereditary amyloidosis subtypes, we describe here a specific case of Apolipoprotein AI amyloidosis (AApoAI), where the diagnosis began from an almost asymptomatic hepatomegaly followed by the development of primary hypogonadism. Baseline laboratory tests showed increased liver enzymes, while imaging tests revealed a suspected infiltrative liver disease. Patient underwent into liver biopsy and histological examination detected the presence of periodic acid-Schiff (−) and Congo-red (+) amorphous eosinophilic material within normal liver tissue. In the typing of amyloid by immunoelectron microscopy, the liver appeared heavily infiltrated by anti-apoAI (+) amyloid fibrils. Gene sequencing and mutational analysis revealed a single-base mutation at position c.251 T > C resulting in an amino acid substitution from leucine to proline in the mature ApoAI protein. This amino acid change led to lower cleavage and ApoAI deposition into the involved organs. Few years later, our patient remaining without treatment, came with symptoms consistent with primary hypogonadism but testicular involvement with ApoAI deposits could not be proven since the patient refused testicular biopsy. Based on this case, we recap the diagnostic challenges, the clinical manifestations, and the potential treatment options for this indolent hereditary amyloidosis subtype. Conclusions: This case-report enlarges the clinical picture of ApoAI-driven disease and its complex genetic background and in parallel suggests for a more systematic approach in any case with strong suspicion of hereditary amyloidosis. © 2019 The Author(s).
Συγγραφείς:
Moutafi, M.
Ziogas, D.C.
Michopoulos, S.
Bagratuni, T.
Vasileiou, V.
Verga, L.
Merlini, G.
Palladini, G.
Matsouka, C.
Dimopoulos, M.A.
Kastritis, E.
Περιοδικό:
BMC Medical Genetics
Εκδότης:
BioMed Central Ltd.
Λέξεις-κλειδιά:
alkaline phosphatase; apolipoprotein A1; aspartate aminotransferase; testosterone; APOA1 protein, human; apolipoprotein A1, adult; amino acid substitution; APOA1 gene; apolipoprotein AI amyloidosis; Article; azoospermia; case report; clinical article; erectile dysfunction; familial amyloidosis; genetic variability; hepatomegaly; heterozygote; human; hypogonadism; immunoelectron microscopy; liver biopsy; male; middle aged; mutational analysis; nucleic acid base substitution; point mutation; Sanger sequencing; DNA sequence; familial amyloidosis; genetic association study; genetic predisposition; genetics; single nucleotide polymorphism, Amino Acid Substitution; Amyloidosis, Familial; Apolipoprotein A-I; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Sequence Analysis, DNA
DOI:
10.1186/s12881-019-0755-5
