Introduction
Ataxia-telangiectasia (A-T) is a rare autosomal recessive inherited progressive neurodegenerative disorder, with onset in early childhood. The average prevalence of the disease is estimated at 1/100,000 children worldwide. To date, the prevalence of A-T in the population of the Republic of Korea is suggested to be extremely low, with only two cases genetically confirmed thus far.
Case report
A 5-year-old boy visited with a chief complaint of progressive gait unsteadiness since the beginning of independent walking at 12 months of age. His perinatal and neonatal histories were unremarkable. He was the third child of healthy, non-consanguineous Korean parents. The family history was unremarkable for neurodegenerative disease. He had no history of recurrent infectious diseases. Upon physical examination, he exhibited normal growth with relative macrocephaly. Ocular telangiectasia was observed but not obvious. Neurological examination revealed no nystagmus or oculomotor apraxia. He exhibited progressive slurred speech, progressive gait and truncal ataxia, choreoathetosis, and both ankle plantar flexor and extensor spasticity with normal muscle strength. Babinski sign was not shown, and deep tendon reflex was not elicited. He exhibited a mild intellectual disability with a Full Scale Intelligence Quotient of 61, as measured by the Korean-Wechsler Preschool and Primary Scale of Intelligence. Serially checked brain magnetic resonance imaging suggested diffuse cerebellar atrophy with enlarged cerebellar sulci and compensatory dilation of posterior fossa. Serum immunoglobulin levels were all within normal limits. His alpha-fetoprotein level was markedly elevated (182.4 ng/ml, normal range < 10 ng/ml).
G-banding of chromosomes from the patient’s peripheral blood lymphocytes was normal (46, XY). Genomic DNA was extracted from patient’s peripheral blood leukocytes, and sequencing was performed on an Illumina NextSeq500 platform (Illumina Inc., San Diego, CA, USA) at Green Cross Genome (Yongin, Republic of Korea). We identified and confirmed two novel heterozygous variants of ATM, a c.5288_5289insGA (p.Tyr1763*) and a c.8363A>C (p.His2788Pro) mutations, by Sanger sequencing in the patient and his parents. His father was heterozygous for the c.5288_5289insGA (p.Tyr1763*) mutation, and his mother was heterozygous for the c.8363A>C (p.His2788Pro) missense mutation.
Conclusion
We report a Korean boy with clinical features including progressive gait and truncal ataxia, choreoathetosis, dysarthria, spasticity of both ankles, and mild intellectual disability. He was identified as two novel compound heterozygote mutations. Patients exhibiting possible diverse clinical features during early childhood should be considered for A-T. Early genetic analysis using a multigene panel, including ATM, is recommended for early and accurate diagnosis. Our results thus expand the spectrum of mutations and phenotypes in A-T.
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