No abstract

A 39-year-old man of Ecuadorian descent presented with a history of seizures, visual impairment, and ataxia. He had a normal birth and early developmental history. His first seizure was a generalized tonic-clonic seizure (GTCS) at 16 years old. Around the same time, he also started experiencing 1-2 myoclonic jerks per day. The myoclonic jerks progressively worsened over a period of 20 years to 15-20 episodes per day. GTCS continued to occur 1-2 times a year until the age of 24 years. EEG revealed multiple brief myoclonic seizures and generalized slow spike/polyspike wave complexes consistent with primary generalized epilepsy. Despite valproic acid, zonisamide, and clonazepam, his seizure control remained poor. When he was 30 years old, he began to have blurring of his vision; ophthalmologic evaluation at that time revealed bilateral cherry-red spots. Optical coherence tomography showed hyperreflectivity in the superficial layers of the retina at the posterior pole consistent with abnormal storage in the ganglion cells. An electroretinogram showed normal rod and cone responses. Flash visual evoked responses demonstrated a delay in the P100 response consistent with dysfunction of the visual pathways. His medical and family history was otherwise noncontributory. Gross physical examination was within normal limits. Neurologic examination demonstrated severe myoclonus of the face interrupting his speech, frequent myoclonus of the arms, truncal and appendicular ataxia, and broad-based ataxic gait. MRI of the brain with and without gadolinium was normal. Chromosome single nucleotide polymorphism microarray revealed long contiguous regions of allele homozygosity (>10 MB) in multiple chromosomes. A query of the regions of homozygosity that was subsequently narrowed down using his clinical presentation identified NEU1 as a candidate gene. Sequencing of NEU1 revealed a homozygous missense mutation c.629C>T (p.Pro210Leu). Enzymatic testing in fibroblasts showed sialidase activity to be deficient (0 nmol/h/mg; ref: 23-74). β-Galactosidase activity was within normal limits.