Ataxia-telangiectasia: atypical presentation and toxicity of cancer treatment

Can J Neurol Sci. 2009 Jul;36(4):462-7. doi: 10.1017/s0317167100007794.

Abstract

Background: The onset of progressive cerebellar ataxia in early childhood is considered a key feature of ataxia-telangiectasia (A-T), accompanied by ocular apraxia, telangiectasias, immunodeficiency, cancer susceptibility and hypersensitivity to ionizing radiation.

Methods: We describe the clinical features and course of three Mennonite children who were diagnosed with A-T following the completion of therapy for lymphoid malignancies.

Results: Prior to cancer therapy, all had non-progressive atypical neurological abnormalities, with onset by age 30 months, including dysarthria, dyskinesia, hypotonia and/or dystonia, without telangiectasias. Cerebellar ataxia was noted in only one of the children and was mild until his death at age eight years. None had severe infections. All three children were "cured" of their lymphoid malignancies, but experienced severe adverse effects from the treatments administered. The two children who received cranial irradiation developed supratentorial primitive neuroectodermal tumors of the brain, an association not previously described, with fatal outcomes.

Conclusions: The range of neurological presentations of A-T is broad. Ataxia and telangiectasias may be minimal or absent and the course seemingly non-progressive. The diagnosis of A-T should be considered in all children with neuromotor dysfunction or peripheral neuropathy, particularly those who develop lymphoid malignancies. The consequences of missing the diagnosis may be dire. Radiation therapy and radiomimetic drugs should be avoided in individuals with A-T.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Agents / adverse effects*
  • Ataxia Telangiectasia / blood
  • Ataxia Telangiectasia / chemically induced*
  • Ataxia Telangiectasia / diagnosis*
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / metabolism
  • Child
  • Child, Preschool
  • DNA-Binding Proteins / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Nerve Tissue Proteins / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Protein Serine-Threonine Kinases / metabolism
  • Retrospective Studies
  • Tumor Suppressor Proteins / metabolism
  • alpha-Fetoproteins / metabolism

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • Tumor Suppressor Proteins
  • alpha-Fetoproteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases