35-year-old female born out of second degree consanguineous marriage with no significant family history presenting with a progressive neurological deficit for 5 years in the form of involuntary movements involving neck and limbs since 4 years having eating dystonia and off late tics. Her speech was dysarthric. There was a history of seizures but no definite history of cognitive impairment, cranial nerves, long tract or sensory involvement. She is not a known case of Diabetes/Hypertension or Tuberculosis. Her diagnosis was Chorea with eating dystonia, tics, seizures and mild parkinsonism features. Structures involved were basal ganglion, cortex.

Differential diagnosis was following:

1. Wilsons disease.
2. Neurodegenerative with brain iron accumulation.
3. Huntingtons disease   
4. Neuroacanthocytosis
5. Huntington disease like

All her investigations were normal other than peripheral blood smear. Her peripheral blood smear revealed presence of 19% acanthocytes (figure 1-3). Given the history, a possibility of a Neuroacanthosis, Choreoacanthosis was suggested. This was confirmed by gene mutation study which revealed VPS13 A mutation to be homozygous positive at intron 26.

Acanthocytes are a type of red blood cells which are denser, slightly contracted and the cell surface has unevenly spaced spiky projection. Neuroacanthocytosis is an autosomal recessive or dominant inherited disease characterized by widespread, non-specific nervous system symptoms, and spiculated “acanthocytic” red blood cells. The clinical manifestations typically involve chorea and dystonia, or a range of other movement disorders (1). Acanthocytes are not commonly present in peripheral blood. To avoid false positives caused by experimental artefacts or echinocytes, pathological conditions are suspected only when more than 3% of acanthocytes appear in the peripheral blood (2). Many times the look for acanthocytes as diagnostic criteria in the peripheral blood smear can be misleading because of the different sensitivities of different methods and subjective interpretation. Also sometimes they appear in later stages of the disease (3). The percentage of acanthocytes in the blood of chorea-acanthocytosis patients is highly variable, usually between 5% and 50%. It does not seem to be correlated with the severity of the disease (4).

References:

1. Zhang L, Wang S, Lin J. Clinical and molecular research of neuroacanthocytosis. Neural Regen Res. 2013 Mar 25;8(9):833-42. doi: 10.3969/j.issn.1673-5374.2013.09.008. PMID: 25206731; PMCID: PMC4146083.

2. Hardie RJ, Pullon HW, Harding AE, et al. Neuroacanthocytosis. A clinical, haematological and pathological study of 19 cases. Brain. 1991;114(Pt 1A):13–49. [PubMed] [Google Scholar] [Ref list]

3. Bayreuther C, Borg M, Ferrero-Vacher C, et al. Chorea-acanthocytosis without acanthocytes. Rev Neurol. 2010;166(1):100–103. [PubMed] [Google Scholar] [Ref list]

4.Rampoldi L., Danek A., Monaco A. P. (2002). Clinical features and molecular bases of neuroacanthocytosis. J. Mol. Med. 80 475–491. 10.1007/s00109-002-0349-z [PubMed] [CrossRef] [Google Scholar] [Ref list]