Chorea‐Acanthocytosis Without Acanthocytosis: Sensory Neuronopathy and Epilepsy as Prominent Features From a Novel VPS13A Variant

Abstract

A 29‐year‐old woman with a novel homozygous VPS13A frameshift variant presented with drug‐resistant temporal‐lobe epilepsy and severe sensory neuronopathy, but no acanthocytes on repeated blood smears—expanding the phenotypic spectrum of chorea‐acanthocytosis beyond its defining haematological feature.

Chorea‐acanthocytosis (ChAc; OMIM #200150) is caused by biallelic loss‐of‐function variants in VPS13A and classically presents with chorea, orofacial dystonia, psychiatric disturbance and red‐cell acanthocytosis [1]. Epilepsy affects 40%–50% of patients but is rarely the presenting feature, and peripheral nerve involvement is usually a mild sensorimotor polyneuropathy rather than a severe sensory neuronopathy [2]. We report a patient whose presentation was dominated by drug‐resistant temporal‐lobe epilepsy and a pure sensory neuronopathy, in whom repeated blood smears never showed acanthocytes.

A 29‐year‐old woman, born to first‐cousin Moroccan parents, presented with a 13‐year history beginning at 16 with obsessive‐compulsive behaviour, depression and florid psychosis, treated as a primary psychotic disorder. At 25 she developed drug‐resistant focal seizures arising from the right temporal lobe with secondary generalisation. Three years later, subtle generalised chorea, orofacial dystonia with tongue biting and head drops from axial hypotonia emerged. Examination showed diffuse hypotonia, complete areflexia and impaired proprioception. Electroneuromyography showed normal motor conduction but unrecordable or severely attenuated sensory potentials in all four limbs, the hallmark of a sensory neuronopathy rather than a length‐dependent neuropathy [3]. Brain MRI showed isolated bistriatal atrophy (Figure 1). Creatine kinase was normal, and acanthocytes were absent on three separate blood smears. An affected sister had shown a similar phenotype and died by suicide at 24, without molecular diagnosis.

FIGURE 1.

Axial (a) and coronal (b) T2‐weighted brain MRI at 29 years showing marked symmetrical atrophy of the caudate nuclei (orange arrow) and putamen (blue arrow). [Colour figure can be viewed at wileyonlinelibrary.com]

Whole‐exome sequencing identified a homozygous frameshift variant in VPS13A, NM_033305.3:c.5286_5289del; p.(Asn1763CysfsTer7), predicted to trigger nonsense‐mediated decay and complete loss of chorein. This variant has not been previously reported and is classified as pathogenic under ACMG‐AMP criteria, confirming ChAc. A combined neurological and psychiatric regimen (lacosamide, valproic acid, phenobarbital, neuroleptics and antidepressants) improved seizure frequency and psychosis but not obsessive‐compulsive symptoms. The patient died at home several months later during a suspected prolonged seizure or post‐ictal event, without hospital care.

This case adds three points to the VPS13A phenotype. First, drug‐resistant temporal‐lobe epilepsy can dominate the clinical picture, as previously described in a Tunisian‐Jewish cohort with diagnostic delays of up to 13 years [4]; ours extends this observation to a different population. Second, sensory neuronopathy is, to our knowledge, exceptional in ChAc, which usually causes a length‐dependent axonal sensory‐motor polyneuropathy [5]; this argues for systematic sensory conduction studies in suspected cases. Third, acanthocytes and creatine kinase were both persistently normal, confirming that their absence does not exclude the diagnosis. Given the diagnostic delay and the sister's unexplained death, ChAc should be considered early in young adults with treatment‐resistant psychiatric symptoms, focal epilepsy or unexplained sensory neuronopathy and genetic counselling offered to at‐risk relatives once a molecular diagnosis is confirmed.

Author Contributions

N.B. and A.B. supervised the clinical and molecular work‐up; L.T. examined the patient, collected the clinical data and drafted the manuscript all authors reviewed and approved the final manuscript.

Ethics Statement

Institutional ethics committee approval was not required for this single‐patient case report, in accordance with the policy of Ibn Sina University Hospital, Rabat. Written informed consent for publication was obtained from the patient's next of kin.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data supporting the findings of this case report are available from the corresponding author upon reasonable request, subject to patient privacy restrictions.