A 19-year-old woman presented with a history of progressive dystonic and ataxic gait disorder of unknown etiology since early childhood. History was significant for diffuse large B-cell lymphoma and severe combined immunodeficiency. The patient had one healthy younger sister and another sister suffering from similar neurologic symptoms. Both parents were healthy and there was no consanguinity.
Neurological examination was remarkable for oculomotor apraxia, scanning dysarthria, severe ataxia of the limbs, ataxia of stance and gait, and dystonic posturing of the right arm and leg. Cognition was unimpaired. Inspection of the eyes revealed ocular telangiectasias (Figure, Panel A). Cerebral magnetic resonance imaging (MRI) showed marked cerebellar, particularly vermal, atrophy (Figure, Panel B). Serum alpha-fetoprotein (AFP) level was considerably increased. Single gene sequencing of the ATM-gene (ataxia telangiectasia, mutated) uncovered a compound heterozygous mutation status (p.Tyr1284GInfsX9 in exon 28, p.Arg2032Lys in exon 43) in both affected siblings, confirming a diagnosis of ataxia-telangiectasia (Louis-Bar syndrome). Parental segregation analysis revealed a heterozygous mutation status of the ATM-gene in the patient’s mother (p.Tyr1284GInfsX9) and father (p.Arg2032Lys), respectively.
Figure
Ocular telangiectasias and cerebellar atrophy. Ocular telangiectasias (black arrows) in the patient’s right eye (A) and atrophy of the cerebellar vermis (white arrow) in T1-weighted sagittal cerebral magnetic resonance imaging (B), representing the eponymous features of ataxia-telangiectasia - small, dilated blood vessels in the sclera and ataxia due to progressive cerebellar degeneration.
Immunodeficiency was treated with regular subcutaneous immunoglobulin injections. Neurologic deficits slowly progressed at follow-up visits.
Ataxia-telangiectasia is an autosomal recessive, progressive neurodegenerative disorder, hallmarked by increased cancer risk and radiation sensitivity due to impaired DNA repair, immunodeficiency, progressive ataxia, and ocular telangiectasias. Neuroimaging is characterized by cerebellar atrophy; serum AFP is often elevated, although the cause of this laboratory anomaly remains unclear. The diagnosis is confirmed by genetic testing [1]. While neurologic symptoms cannot be addressed causally, immunodeficiency, increased cancer risk and radiation sensitivity need to be treated or considered accordingly [1].
This case highlights the importance of thorough physical examination to guide targeted genetic testing and establish correct diagnoses in progressive neurological childhood disorders like ataxia-telangiectasia, helping to prevent its secondary complications.
Abbreviations
MRI, magnetic resonance imaging; AFP, alpha-fetoprotein; ATM, ataxia telangiectasia, mutated; DNA, deoxyribonucleic acid.
Ethics and Consent
This study was performed in accordance with the Declaration of Helsinki. The patient has provided written informed consent.
Acknowledgements
We thank the patient for participating in this case study.
Competing Interests
The authors have no competing interests to declare.