A chorea-acanthocytosis patient with novel mutations in the VPS13A gene without acanthocyte.

Chorea-acanthocytosis (ChAc) is a rare clinical genetic disorder of the nervous system, which is characterized by choreiform movement disorder, cognitive decline, and psychiatric disorders. ChAc is mostly diagnosed based on its typical clinical manifestations and the increased number of acanthocytes in peripheral blood smears. Here, we report a patient, who has the characteristic clinical manifestations of ChAc with limb choreiform movements, involuntary lip and tongue bites, seizures, and emotional instability. However, her blood smear was negative for acanthocytes with scanning electron microscopy. We later identified two novel pathogenic mutations in the patient's vacuolar protein sorting homolog 13 A (VPS13A) on chromosome 9q21 by targeted gene sequencing, and she was definitively diagnosed with "ChAc." After treatment with carbamazepine, haloperidol, the patient's symptoms gradually improved. We consider that an acanthocyte negative blood smear cannot rule out ChAC diagnosis, and genetic testing is the "gold standard" for the diagnosis. Through a review of previous research, it is rare for a patient to have a clear diagnosis of ChAc by genetic testing, but whose blood smear is negative for acanthocytes with electron microscopy. In addition, in this report, we discovered two novel pathogenic mutations, which have not been reported previously, and extended the genetic characteristics of ChAc.

Novel pathogenic VPS13A mutation in Moroccan family with Choreoacanthocytosis: a case report.

BACKGROUND: Choreoacanthocytosis (ChAc), is a rare neurodegenerative disease, characterized by movement disorders and acanthocytosis in the peripheral blood smears, and various neurological, neuropsychiatric and neuromuscular signs. It is caused by mutations in VPS13A gene with autosomal recessive pattern of inheritance. CASE PRESENTATION: Here we report two patients belonging to a consanguineous Moroccan family who present with movement disorder pathology. They were suspected to have choreoacanthocytosis according to biological, clinical and radiological finding. Thus, whole-exome sequencing was performed for precise diagnosis and identified a homozygous novel nonsense mutation c.337C > T (p.Gln113*) in exon 5 of VPS13A in the two affected siblings. CONCLUSION: Here, we report a novel nonsense p.Gln113* mutation in VPS13A identified by whole-exome sequencing, which caused ChAc in a Moroccan family. This is the first description of ChAc in Morocco with genetic confirmation, that expands the mutation diversity of VPS13A and provide clinical, neuroimaging and deep brain stimulation findings.

Neuroacanthocytosis: a case report of chorea-acanthocytosis.

Neuroacanthocytosis is a rare progressive neurodegenerative disease, including Chorea-acanthocytosis, McLeod syndrome, Huntington's disease-like 2, and pantothenate kinase-associated neurodegeneration, where Chorea-acanthocytosis occupies the main entity of this disease group. Here, a classic case of Chorea-acanthocytosis is reported that exhibited gradually deteriorating abnormal movements of limbs and face, swallowing difficulty, and lip and cheek biting for the past two years. Peripheral blood smears revealed that 35% of the red blood cells were acanthocytes and electron microcopy scans clearly showed the morphology of acanthocytes. VPS13A gene sequencing found a heterozygous novel VPS13A gene mutation (c.80dupT). Brain magnetic resonance imaging scans showed moderate anterior horn dilation of lateral ventricles and bilateral atrophy of the head of caudate nucleus. Several suggestive features are summarized to provide diagnostic clues for Chorea-acanthocytosis and facilitate future diagnosis and treatment.

Neuroacanthocytosis Syndromes in an Italian Cohort: Clinical Spectrum, High Genetic Variability and Muscle Involvement.

Neuroacanthocytosis (NA) syndromes are a group of genetically defined diseases characterized by the association of red blood cell acanthocytosis, progressive degeneration of the basal ganglia and neuromuscular features with characteristic persistent hyperCKemia. The main NA syndromes include autosomal recessive chorea-acanthocytosis (ChAc) and X-linked McLeod syndrome (MLS). A series of Italian patients selected through a multicenter study for these specific neurological phenotypes underwent DNA sequencing of the VPS13A and XK genes to search for causative mutations. Where it has been possible, muscle biopsies were obtained and thoroughly investigated with histochemical assays. A total of nine patients from five different families were diagnosed with ChAC and had mostly biallelic changes in the VPS13A gene (three nonsense, two frameshift, three splicing), while three patients from a single X-linked family were diagnosed with McLeod syndrome and had a deletion in the XK gene. Despite a very low incidence (only one thousand cases of ChAc and a few hundred MLS cases reported worldwide), none of the 8 VPS13A variants identified in our patients is shared by two families, suggesting the high genetic variability of ChAc in the Italian population. In our series, in line with epidemiological data, McLeod syndrome occurs less frequently than ChAc, although it can be easily suspected because of its X-linked mode of inheritance. Finally, histochemical studies strongly suggest that muscle pathology is not simply secondary to the axonal neuropathy, frequently seen in these patients, but primary myopathic alterations can be detected in both NA syndromes.