Ataxia-telangiectasia-like disorder

Ataxia-telangiectasia-like disorder (ATLD), also known as ataxia-telangiectasia-like disorder 1 (ATLD1), is an extremely rare autosomal recessive neurodegenerative condition caused by biallelic mutations in the MRE11 gene (MRE11A). This gene encodes a protein critical for DNA double-strand break repair, and its dysfunction leads to a clinical presentation that closely resembles classical ataxia-telangiectasia (A-T). The disorder primarily affects the nervous system and immune system. Key clinical features include progressive cerebellar ataxia (difficulty with coordination and balance), dysarthria (slurred speech), oculomotor apraxia (difficulty with voluntary eye movements), and cellular radiosensitivity. Unlike classical ataxia-telangiectasia, patients with ATLD typically do not develop telangiectasias (dilated blood vessels on the skin or eyes), and serum alpha-fetoprotein levels are usually normal. Cerebellar atrophy is commonly observed on brain imaging. Some patients may exhibit mild immunodeficiency, though this is generally less prominent than in classical A-T. The progression of neurological symptoms tends to be slower compared to A-T in many reported cases. There is currently no cure or disease-modifying treatment for ATLD. Management is supportive and symptomatic, focusing on physical therapy and rehabilitation to maintain mobility, speech therapy for dysarthria, and monitoring for potential immunological complications or malignancies. Due to the underlying DNA repair defect, patients have increased chromosomal instability and may have an elevated risk of cancer, though the precise cancer risk in ATLD remains less well-characterized than in A-T given the very small number of reported cases worldwide. Genetic counseling is recommended for affected families.

Common questions about Ataxia-telangiectasia-like disorder