Ataxia with Oculomotor Apraxia Type 1 without Oculomotor Apraxia: A Case Report.

Dear Editor, Ataxia with oculomotor apraxia type I (AOA1) is a recessively inherited ataxic disorder that is characterized clinically by the childhood onset of progressive cerebellar ataxia, oculomotor apraxia (OMA), and peripheral axonal sensorimotor neuropathy.1 Dystonia, chorea, and cognitive impairment are commonly associated symptoms, and hypoalbuminemia and hypercholesterolemia are often observed.2 AOA1 is caused by mutations of the gene encoding aprataxin (APTX).3 AOA1 has not been reported previously in Korea.5 The first case of AOA1 in Korea is presented here. In this patient, who did not exhibit OMA but had bilateral gaze-evoked nystagmus, the condition was caused by compound heterozygous mutations of APTX. A 32-year-old man presented with slowly progressive gait disturbance and unsteadiness that developed at the age of 14 years. He was the second child of healthy unrelated Korean parents without a family history of gait disturbance. He was diagnosed as having cerebellar atrophy of unknown cause at the age of 17 years. His ataxic gait had progressively deteriorated and he had become confined to a wheelchair 2 years prior to presentation. A physical examination revealed pes cavus but no scoliosis or other musculoskeletal deformity. A neurological examination revealed mild cerebellar dysarthria without dysphagia. His limb motor powers were normal, as were light touch, pinprick, temperature, and pain sensations. However, his vibration and positional senses were decreased in the lower limbs, his deep tendon reflexes were hyporeflexic in all the limbs, Babinski signs were absent bilaterally, and he had bilateral upper and lower limb dysmetria and truncal ataxia. The patient was unable to stand still without assistance. His ranges of extraocular movement were full in all directions, and he did not exhibit OMA on reflexive saccades testing, but his optokinetic nystagmus was impaired. He presented gaze-evoked nystagmus in all directions. His Mini-Mental State Examination score was 30. The results of laboratory tests were unremarkable except for hypercholesterolemia (217 mg/dL), hypoalbuminemia (3.3 g/dL), and mildly elevated alpha-fetoprotein (7.05 ng/mL). A nerve conduction study and electromyography revealed sensorimotor axonal polyneuropathy, and brain magnetic resonance imaging revealed pure cerebellar atrophy without involvement of the pons, medulla oblongata, midbrain, or cerebral cortex (Fig. 1A and B). Sanger sequencing after PCR amplification of APTX revealed compound heterozygous mutations involving the deletion of two nucleotides (c.359_360delAC, p.Asp120Lysfs2) in exon 3, and a missense mutation (c.617C>T, p.Pro206Leu, rs121908131) in exon 5 (Fig. 1C). While the mutation of c.359_360delAC is novel, c.617C>T is a known pathogenic mutation. The patient’s father is a carrier of the single heterozygous mutation (c.617C>T); we were unable to perform genetic testing on his mother. While Friedreich’s ataxia is the most frequent cause of autosomal recessive ataxia in the Caucasian population,6 it is rare in Korea and Japan.5,7 Before discovery of the APTX mutation, AOA1 was known as early-onset ataxia with OMA and hypoalbuminemia (EAOH) in Japan Minwoo Lee Nan Young Kim Jin Young Huh Young Eun Kim Yun Joong Kim