Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis.
BACKGROUND
Hereditary, autosomal dominant amyloidosis, caused by mutations in the genes encoding transthyretin, fibrinogen A alpha-chain, lysozyme, or apolipoprotein A-I, is thought to be extremely rare and is not routinely included in the differential diagnosis of systemic amyloidosis unless there is a family history.


METHODS
We studied 350 patients with systemic amyloidosis, in whom a diagnosis of the light-chain (AL) type of the disorder had been suggested by clinical and laboratory findings and by the absence of a family history, to assess whether they had amyloidogenic mutations.


RESULTS
Amyloidogenic mutations were present in 34 of the 350 patients (9.7 percent), most often in the genes encoding fibrinogen A alpha-chain (18 patients) and transthyretin (13 patients). In all 34 of these patients, the diagnosis of hereditary amyloidosis was confirmed by additional investigations. A low-grade monoclonal gammopathy was detected in 8 of the 34 patients (24 percent).


CONCLUSIONS
A genetic cause should be sought in all patients with amyloidosis that is not the reactive systemic amyloid A type and in whom confirmation of the AL type cannot be obtained.
Lachmann
Helen J
HJ
National Amyloidosis Centre, Department of Medicine, Royal Free and University College Medical School, Royal Free Campus, London, United Kingdom.
Booth
David R
DR
Booth
Susanne E
SE
Bybee
Alison
A
Gilbertson
Janet A
JA
Gillmore
Julian D
JD
Pepys
Mark B
MB
Hawkins
Philip N
PN
D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000175:diagnosis* / Q000235:genetics; D028226:Amyloidosis, Familial / Q000150:complications / Q000175:diagnosis*; D016632:Apolipoprotein A-I / Q000235:genetics; D004252:DNA Mutational Analysis; D003951:Diagnostic Errors; D005260:Female; D005340:Fibrinogen / Q000235:genetics; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007668:Kidney / Q000000981:diagnostic imaging / Q000473:pathology; D008875:Middle Aged; D009113:Muramidase / Q000235:genetics; D010265:Paraproteinemias / Q000150:complications; D017354:Point Mutation; D011228:Prealbumin / Q000235:genetics; D011877:Radionuclide Imaging
D016632:Apolipoprotein A-I; D011228:Prealbumin; D005340:Fibrinogen; D009113:Muramidase