RT Book, Section
A1 Koenig, Michel
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1181479822
T1 Friedreich Ataxia and AVED
T2 The Online Metabolic and Molecular Bases of Inherited Disease
YR 2019
FD 2019
PB McGraw-Hill Education
PP New York, NY
SN 9780071459969
LK ommbid.mhmedical.com/content.aspx?aid=1181479822
RD 2024/04/25
AB In  1863,  Nicholaus  Friedreich,  Professor  of  Medicine  in  Heidelberg,  described  a  “degenerative  atrophy  of  the  posterior  columns  of  the  spinal  cord”  leading  to  progressive  ataxia,  sensory  loss  and  muscle  weakness,  often  associated  with  scoliosis,  foot  deformity,  and  cardiopathy.1,2  Not  until  the  late  1970s  were  large  series  of  patients  analyzed  to  establish  clear  diagnostic  criteria.3,4  Recessive  inheritance  was  firmly  established  as  an  essential  feature  of  Friedreich  ataxia  (FRDA).3-6  The  Québec  Collaborative  Group  identified  the  clinical  features  of  typical  FRDA  and  proposed  them  as  diagnostic  criteria.3  They  were,  however,  too  strict  for  the  diagnosis  of  early  cases.  Harding  distinguished  the  early  signs  and  symptoms  from  those  that  may  not  be  present  at  the  onset,  but  that  have  to  manifest  as  the  disease  evolves4  (Table  281-1).  These  studies,  as  well  as  more  recent  ones,7,8  identified  an  important  degree  of  clinical  variability,  both  among  and  within  the  families.  Atypical  FRDA,  including  adult-onset  Friedreich  ataxia  (LOFA)9,10  (MIM  229300),  and  Friedreich  ataxia  with  retained  reflexes  (FARR),  a  variant  in  which  tendon  reflexes  in  the  lower  limbs  are  preserved,11  were  recognized  by  genetic  linkage  studies  to  be  part  of  the  same  entity.  The  identification  of  the  most  common  FRDA  mutation,  an  unstable  hyperexpansion  of  a  GAA  triplet  repeat  polymorphism,12  clarified  the  origin  and  mechanism  of  the  clinical  variations.