Hereditary amyloidosis in early childhood associated with a novel insertion-deletion (indel) in the fibrinogen Aalpha chain gene.
BACKGROUND
Systemic amyloidosis occurring in early childhood is extremely rare, and is usually of AA type complicating chronic inflammatory diseases. We report the molecular basis of amyloidosis in a Korean girl who presented at 7 years of age with asymptomatic proteinuria and developed amyloid hepatomegaly and end-stage renal failure within 2 years.


METHODS
Renal biopsy showed enlarged glomeruli virtually replaced by amyloid, but without interstitial or vascular involvement. The histologic appearance was identical to that seen in patients with hereditary fibrinogen Aalpha chain Glu526Val amyloidosis, and the amyloid deposits stained specifically with antibodies to fibrinogen. Mutations were sought in the genes of the amyloidogenic proteins, transthyretin, apolipoprotein AI, lysozyme and fibrinogen Aalpha chain genes by polymerase chain reaction (PCR) and sequencing.


RESULTS
A unique frameshift insertion-deletion (indel) mutation was identified in one allele of her fibrinogen Aalpha chain gene, which encodes a partly novel peptide and a premature stop signal, similar to the two previously reported amyloidogenic point deletions at codons 522 and 524 in this molecule. The mutation was absent in samples verified to be from her parents, indicating that it had occurred de novo.


CONCLUSIONS
This is the first description of hereditary fibrinogen Aalpha chain amyloidosis in an Asian individual, and the distinctive renal histology offered a strong clue to the diagnosis. The disease is potentially curable by combined hepatorenal transplantation.
Kang
Hee Gyung
HG
Department of Pediatrics, Seoul National University Medical School, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
Bybee
Alison
A
Ha
Il Soo
IS
Park
Moon Soo
MS
Gilbertson
Janet A
JA
Cheong
Hae Il
HI
Choi
Yong
Y
Hawkins
Philip N
PN
D000595:Amino Acid Sequence; D028226:Amyloidosis, Familial / Q000235:genetics* / Q000473:pathology; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002648:Child; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D016368:Frameshift Mutation; D017353:Gene Deletion; D006801:Humans; D007723:Korea; D008969:Molecular Sequence Data
C464794:fibrinogen Aalpha; D005340:Fibrinogen