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Prevalence is estimated to be 1/100,000 live births.

The first manifestations usually occur at 1-2 years of age with progressive walking difficulties, balance disorders followed by slurred speech, drooling and oculomotor apraxia. Choreoathetosis may appear around 9-10 years of age and worsen progressively. Intelligence is normal although slurred speech and drooling may be interpreted as intellectual deficiency. Cutaneo-mucosal telangiectasias (especially of the conjunctivae) usually appear around 3-6 years of age, or later. Immunodeficiency causes recurrent airway infections (otitis, sinusitis, bronchitis, pneumonia) which can lead to bronchiectasis and autoimmune/inflammatory features such as granulomas (mostly of the skin but also other organs); its severity varies widely between patients, from severe lymphopenia (including severe combined immune deficiency and/or severe hypogammaglobulinemia) to no overt biological abnormality. There is a high risk of malignancy, particularly of lymphoma and leukemia (in childhood and adolescence mostly), and carcinomas (in adulthood). Patients are highly sensitive to ionizing radiation, that are forbidden. X-rays imaging must be avoided. Other features include growth delay, infertility, glucose intolerance, non-alcoholic steatohepatitis.

Ataxia-telangiectasia (A-T) is caused by loss of function biallelic (homozygous or compound heterozygous) pathogenic variants (PVs) of the ATM gene (11q22.3) which encodes a protein kinase involved in double-strand-break DNA repair, notably in the Purkinje cells of the cerebellum and cutaneous and conjunctival endothelial cells. PVs induce stop codons or directly inactivate the kinase domain; some are hypomorphic and lead to an attenuated disease with late onset symptoms and dystonia.

Early diagnosis is difficult. Quasi-constant very high serum level of alpha-fetoprotein is a useful clinical sign. Cytogenetic analysis may help confirm the diagnosis (7;14 translocations) but few laboratories still perform it. Molecular analysis of the ATM gene confirms the diagnosis. Multigene panels for ataxias or immune deficiencies have now greatly facilitated A-T diagnosis and other differential diagnoses.

The differential diagnosis includes ataxia-telangiectasia-like disorder and ataxia-oculomotor apraxia types 1 and 2.

Antenatal and preimplantation genetic diagnosis are possible when pathogenic variants have been identified in a family.

Genetic counseling should be discussed due to the severity and incurability of the disease. Siblings of an affected individual have a 25% chance of being affected. The risk for couples with one PV carrier to have an affected child is estimated at 1/600-800. PV carriers are estimated to represent 1/150-200 of the general population. Genetic testing of the spouse may be discussed.

There is no curative therapy. Management is symptomatic and involves physiotherapy, speech therapy and treatment of the infection and pulmonary complications (chronic antibiotic prophylaxis and/or human polyvalent normal Immunoglobulin long-term replacement therapy). The cells of A-T patients show increased susceptibility to ionizing radiation; X-rays, radiotherapy, and some forms of chemotherapy should be used with caution or avoided. Affected children with classical A-T are often wheelchair bound by 10-11 years old. Beta-blockers may reduce trembling and improve fine movements performance. Nicotinamide riboside brings minor improvements of some neurological symptoms. Dexamethasone administration through autologous erythrocytes has shown promising results on neurologic features in clinical trials. Gene therapy using antisense oligonucleotides is currently under trial.

The prognosis is severe due to the occurrence of respiratory infections, neurodegeneration, accelerated cutaneo-mucosal ageing and an increased risk of cancer (35% of patients develop cancer by the age of 20).