The clinical spectrum of ataxia telangiectasia in a cohort in Sweden
Hannes Lindahl,
Eva Svensson,
Annika Danielsson,
Andreas Puschmann,
Per Svenningson,
Bianca Tesi,
Martin Paucar
Affiliations
Hannes Lindahl
Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Corresponding author. Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
Eva Svensson
Department of Pediatric Neurology, Karolinska University Hospital, Stockholm, Sweden
Annika Danielsson
Department of Pediatric Neurology, Sachska Children's Hospital, Stockholm, Sweden
Andreas Puschmann
Neurology, Department of Clinical Sciences Lund, Lund University, Sweden; Skane University Hospital, Lund, Sweden; SciLifeLab National Research Infrastructure, Sweden
Per Svenningson
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neurology, Karolinska University Hospital, Stockholm, Sweden
Bianca Tesi
Department of Clinical Genetics and Genomics, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden
Martin Paucar
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neurology, Karolinska University Hospital, Stockholm, Sweden
Ataxia telangiectasia (A-T), caused by biallelic variants in the ATM gene, is a multisystemic and severe syndrome characterized by progressive ataxia, telangiectasia, hyperkinesia, immunodeficiency, increased risk of malignancy, and typically death before the age of 30. In this retrospective study we describe the phenotype of 14 pediatric and adult A-T patients evaluated at the Karolinska University Hospital in Sweden during the last 12 years. Most of the patients in this cohort were severely affected by ataxia and wheelchair use started at a median age of 9 years. One patient died before the age of 30 years, but five patients had survived beyond this age. Four patients received prophylactic immunoglobulin replacement therapy due to hypogammaglobulinemia and respiratory complications ranged from mild to moderate severity. Three patients developed type 2 diabetes in young adulthood and nine patients (64%) had a history of elevated liver function tests. Four patients were diagnosed with cancer at ages 7, 41, 47, and 49 years. All the ATM variants in these patients were previously reported as pathogenic except one, c.6040G > A, which results in a p.Glu2014Lys missense variant. With increased life expectancy, A-T complications such as diabetes type 2 and liver disease may become more common. Despite having severe neurological presentations, the A-T patients in this case series had relatively mild infectious and respiratory complications.
