2023 American Academy of Neurology Abstract Website

Objective:

Background:

Design/Methods:

We present a patient with persistently elevated creatinine kinase and a clinical syndrome consistent with adult-onset spinal muscular atrophy (dSMA) without pontocerebellar atrophy secondary to a vaccinia-related kinase 1 (VRK1) mutation.

Results:

A 46-year-old male presented for evaluation of persistently elevated creatinine kinase, leg weakness, and decreased balance for more than 5 years. He reported mild weakness mainly in the lower extremities and reduced calf size. The patient has had persistently elevated creatine kinase (CK) for the past 5 years, ranging from 580-7,000 units/L.

On examination, he had bilateral high arches, calf fasciculations, and atrophy. Motor showed decreased strength in feet dorsiflexion and minimal bilateral hand interosseous weakness. Reflexes were normal except for the absent left ankle reflex. The rest of the neurologic examination was unremarkable.

EMG/NCS showed reduced motor responses with diffuse neurogenic changes in the right arm and leg concerning for motor neuropathy. CK level remained elevated along with aldolase; otherwise negative myopathy labs. The neuropathy panel showed two pathogenic mutations of the VRK1 gene, variant c1072C>T (p.Arg358) and c.356 A>G (p.His119Arg), consistent with compound heterozygosity.

Conclusions:

VRK1 mutation is a rare cause of distal predominant spinal muscular atrophy. This disease is characterized by slowly progressive distal symmetric limb muscle weakness and atrophy, frequently leading to foot deformities such as pes cavus, with minimal or no sensory involvement. Mild elevations in CK can be seen in up to 50% of motor neuron disease cases.

Our patient's presentation was consistent with adult-onset spinal muscular atrophy. There was no pontocerebellar hypoplasia, which has also been described with this mutation. Creatine kinase level remained very elevated in our patient, beyond what has previously been described in the literature. Future investigation should be done to determine the significance of this, including whether there may be a myopathic component to this illness.