Neuropathology in classical and variant ataxia-telangiectasia.
Ataxia-telangiectasia (A-T) is classically characterized by progressive neurodegeneration, oculocutaneous telangiectasia, immunodeficiency and elevated α-fetoprotein levels. Some patients, classified as variant A-T, exhibit a milder clinical course. In the latter patients extrapyramidal symptoms, instead of cerebellar ataxia, tend to be the dominating feature and other classical disease hallmarks, like telangiectasia, appear later or even may be absent. Some patients with variant disease have clinically pronounced anterior horn cell degeneration. Neuropathological studies of genetically proven A-T patients are lacking. The aims of our study were to describe the neuropathology of three A-T patients; in two of them the diagnosis was genetically confirmed. The neuropathological findings were compared with those of all known published autopsy findings in A-T patients up to now. Two classical A-T patients aged 19 and 22 and a 33-year-old patient with variant disease were autopsied. In line with previous reports, our patients had severe cerebellar atrophy, less pronounced degeneration of the dentate nucleus and inferior olive, degeneration of the posterior columns and neurogenic muscular atrophy. In addition, all three had anterior horn cell degeneration, which was most prominent at the lumbar level. Compared to the literature, the degenerative changes in the brain stem of the variant A-T patient were somewhat less than anticipated for his age. Degenerative changes in the cerebellum and spinal cord were comparable with those in the literature. Progeric changes were lacking. In conclusion, compared to classical A-T, the variant A-T patient showed essentially the same, only slightly milder neuropathological abnormalities, except for anterior horn degeneration.
Department of Pediatric Neurology, Donders Institute for Brain, Cognition and Behaviour Pathology, Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands.
Mijke M M
MM
Verhagen
Jean-Jacques
JJ
Martin
Marcel
M
van Deuren
Chantal
C
Ceuterick-de Groote
Corry M R
CM
Weemaes
Berry H P H
BH
Kremer
Malcolm A R
MA
Taylor
Michèl A A P
MA
Willemsen
Martin
M
Lammens
D000328:Adult; D001260:Ataxia Telangiectasia / Q000473:pathology*; D064007:Ataxia Telangiectasia Mutated Proteins; D001344:Autopsy; D006528:Carcinoma, Hepatocellular / Q000150:complications; D002423:Cause of Death; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002490:Central Nervous System / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D018450:Disease Progression; D055724:Electrophysiological Phenomena; D017809:Fatal Outcome; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications; D008228:Lymphoma, Non-Hodgkin / Q000150:complications; D008297:Male; D009207:Myoclonus / Q000209:etiology; D009468:Neuromuscular Diseases / Q000209:etiology; D010243:Paralysis / Q000209:etiology; D010610:Pharyngeal Neoplasms / Q000150:complications; D010641:Phenotype; D011434:Proprioception / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D012129:Respiratory Function Tests; D012141:Respiratory Tract Infections / Q000150:complications; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases