Transthyretin Tyr77 familial amyloid polyneuropathy: a clinicopathological study of a large kindred.
More than 40 point mutations (producing different clinical manifestations) have been described in diverse points of the plasma protein transthyretin (TTR). The Met30 is considered the most common mutation, the Tyr77 mutation being the second most prevalent. However, data from patients with this late mutation are scarce, and usually come from isolated case reports or tables. The Tyr77 mutation is not as well characterized as the Met30 mutation, especially with respect to such aspects as prognosis or possible treatment by liver transplantation. We therefore present the clinical and pathological features of an extensive family with the Tyr77 TTR mutation, comprising 12 affected individuals over four generations. Six living individuals were followed over a 10-year period. Retrospective data were obtained with regard to the deceased family members. We found that an initial and sometimes prolonged carpal tunnel syndrome, beginning between the 6th and 7th decades, characterizes the Tyr77 mutation. In most cases this evolved to generalized peripheral nerve involvement, restrictive cardiomyopathy, and intestinal malabsortion. Although survival is usually high, there are progressive cases that should be candidates for liver transplant, before severe impairment has developed.
Blanco-Jerez
C R
CR
S. de Neurobiología, Hospital Ramón y Cajal, Madrid, Spain.
Jiménez-Escrig
A
A
Gobernado
J M
JM
Lopez-Calvo
S
S
de Blas
G
G
Redondo
C
C
García Villanueva
M
M
Orensanz
L
L
D000368:Aged; D000369:Aged, 80 and over; D017772:Amyloid Neuropathies / Q000235:genetics* / Q000473:pathology*; D001342:Autonomic Nervous System Diseases / Q000235:genetics / Q000473:pathology; D001706:Biopsy; D004594:Electrophysiology; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction; D009482:Neurophysiology; D010375:Pedigree; D017354:Point Mutation; D011228:Prealbumin / Q000235:genetics*; D013497:Sural Nerve / Q000473:pathology; D014443:Tyrosine
D011228:Prealbumin; D014443:Tyrosine