Ataxia Telangiectasia: A Case Series from a Consanguineous Marriage

Abstract

Ataxia Telangiectasia (AT) is a rare autosomal recessive disease with features of progressive cerebellar atrophy, immunodeficiency, and enhanced cancer susceptibility due to mutations in the ataxia telangiectasia mutated (ATM) gene. However, despite evidence from patients with AT in consanguineous Iranian families, limited information is still available on the genotype-phenotype association. This paper presents a familial case series of AT in Yazd, Iran, with a novel homozygous ATM mutation.
This report examines a consanguine family in Yazd, Iran, with four members presenting with symptoms characteristic of AT, including progressive neurological decline, cerebellar atrophy, immunodeficiency, elevated alpha-fetoprotein, and recurrent infections.
Genetic analysis confirmed a novel homozygous mutation of the ATM gene (c.1834C>A; p.Leu612Ile), which is a non-conservative substitution. It is predicted to result in loss of function, and parents were carriers of the mutation. Treatment included intravenous immunoglobulin, prophylactic antibiotics, and supportive care. One of the patients died due to severe infection despite intervention.
This case series highlights the impact of consanguinity on the occurrence of AT and the supporting role of genetic testing in diagnosing ATM mutations. The results emphasize the need for improved genetic counseling, family planning, early immunological therapy, and culturally tailored public health strategies to effectively manage AT in consanguineous populations.