Wednesday, October 14, 2009

Adult onset ataxia telangiectasia (variant AT)

Verhagen MMM, Abdo WF, Willemsen MAAP.  Clinical spectrum of ataxia-telangiectasia in adulthood. Neurology 2009; 73:  430-437 and accompanying editorial.
This important article describes another way adult neurologists cannot completely hide from their brief 3 month training in pediatric neurological diseases that they underwent in training. The summary below focuses on clinical aspects but the article contains genetics information for those interested.
AT is typically an AR childhood disease that one can read about in a 1980 edition of Adams and Victor.  Variant AT occurs in older adults as a forme fruste perhaps of the pediatrics form. It is described in about 13 patients.  Patients usually had young onset movement disorders, either choreoathetosis or resting tremor.  Distal muscle weakness occurred in one patient.  By age 27 patients began to experience progressive cerebellar atrophy with eventual development of dysarthria in all, continued movement disorders, nystagmus, dystonias and oculomotor apraxias.  EMG/NCS showed either anterior horn cell involvement or sensorimotor polyneuropathy.  Cerebellar atrophy on imaging affected vermis primarily. 
Minimal  telangiectasias of either eye or skin occurred in variant form.  Lung function was normal.  Four of 13 developed malignancies including ALL, ectopic pituitary tumor, and breast cancer.  Alpha feto protein levels were markedly elevated in all patients  to ten to fifty times normal, although this is still less than in classic AT. Ig deficiencies occurred in only one patient and were of minor degree. 
Adult patients with classic AT also exist and present with cerebellar ataxia, ocular telangiectasia, immunodeficiency, rearrangement of chromosomes 7 and 14, X ray hypersensitivity and elevated alpha feto protein levels.  Patients were all wheelchair bound, had growth retardation, endocrinopathy including type 2 DM, diminished secondary sexual characteristics, restrictive lung disease, and more cancer especially lymphoproliferative diseases.  Defect is in DNA repair. 
Alpha fetoprotein appears to be good screening tool.

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