2 cases of patients with speech difficulties, vocal ticks, then progressing to choreiform movements and finally to dystonias were investigated.
Investigations revealed CK of 600-1200.
Neurophysiology showed mild sensory and motor axonal neuropathy, whereas MRI revealed atrophy of caudate and lentiform nucleus.
DaTSCAN showing decreased uptake in the basal ganglia bilaterally
In both cases peripheral blood films revealed acanthocytes. 25% in the first case and 10-70% in the second case.
Diagnostic test showed compound heterozygous mutations in exon 4 (c.0237del, pE80KfsX11) and 72 (c.9429_9432del, p.R3143SfsX5) of VPS13A in case 1 and compound heterozygous mutations in exon 14 (c.1208_1211del, p.Q403RfsX6) and 56 (c.7867C>T, p.R2623X) of VPS13A confirming the suspected diagnosis of chorea-acanthocytosis.
Chorea acanthocytosis is a rare autosomal recessive disorder affecting ~1000 worldwide and is caused by mutations in VPS13A gene.
Clincial features include chorea, oromandibular dystonia (which may be mutilating) or generalized dystonia, phonic tics, feeding/ tongue protrusion dystonia, head drops, ‘rubber man’ gait, seizures, neuropathy and behavioural disturbance (change in personality, OCD, disinhibition). The latter may be a presenting feature.
Diagnosis of chorea-acanthocytosis is primarily clinical with characteristic MRI findings supplied by evidence of muscle disease. MRI and CT might show dilatation of anterior horn of lateral ventricles and atrophy of the caudate nuclei.
Peripheral blood film may show acanthocytes in 5-50% of the red cell population. It has to be noted, however, that in some cases acanthocytosis may appear later or may be absent altogether. Majority of patients will also have increased creatinine kinase (CK), as exemplified by the two cases described above.
Central nuclei and atrophic fibres will be key findings on muscle biopsy.
There are several causes of neuro-acanthocytosis (oromandibular dystonia as prominent feature ** yes *perhaps)
•Huntington’s disease-like type 2
•Pantothenate kinase associated neurodegeneration (PKAN)*
•Hypoprebetalipoproteinaemia, acanthocytosis, retinitis pigmentosa and pallidal degeneration (HARP) syndrome**
McLeod neuroacanthocytosis syndrome is an X-linked recessive (mutations in XK gene) multisystem disorder with haematological, hepatological, neuromuscular and central nervous system involvement in middle-aged males.
Cardiomyopathy and conduction abnormalities as well as dystonia and chorea are a common finding.
Seizures and oromandibular dystonia are, however, less common than in chorea-acanthocytosis.
Oromandibular dystonia is characterized by prolonged spasms caused by contraction of the muscles of the mouth and mandible. It involves the muscles of facial expression, mastication, tongue and eyelids.
It can be drug-induced, caused by structural lesions or encephalitis. It may also be genetic (e.g. McLeod syndrome, Ataxia-telangiectasia, Wilson’s and HD).
The cases described are examples of chorea- acanthocytosis ( of 21 and 18 year disease duration respectively).
Notably, both patients developed parkinsonism after a decade of disease duration and both had abnormal DaTSCANs showing nigrostratial denervation.
Clinically, progressive parkinsonism appears to evolve in later stages of chorea- acanthocytosis and gradually replaces the hyperkinetic abnormal movements, in a manner similar to that observed in Huntington’s disease and other neurodegenerative causes of chorea. The hypothesis of the nigrostriatal pathway being gradually involved in the neurodegenerative process is further supported by the findings of severe loss of dopamine D2-receptor-bearing striatal neurons and loss of dopaminergic projections from the SN to the posterior putamen in a PET study (unconfirmed case).
This phenotypal shift has clinical implications:
•Withdrawal of neuroleptics and tetrabenazine
•L-dopa use may be limited, amantadine reportedly helps gait
•DBS may be useful in some cases
Useful mnemonic: DEPICTING Chorea
D – Drug induced
E – Endocrine
P – Paraneoplastic/polycythaemia vera
I – Infectious/immune mediated
C – Chorea gravidarum
T – Toxic
I – Ischaemic
N – Neonatal hypoxia
G – Genetic
Bohlega S. Chorea-acanthocytosis: clinical and genetic findings in three families from the Arabian peninsula.. Mov Disord. 2003; 18(4): 403-407.
Baeza V et al. Chorea-Acanthocytosis.. Gene Reviews 2002.
In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Fong CT, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. 2002 Jun 14 [updated 2014 Jan 30].
Schneider R, Hoffman HT. Oromandibular dystonia: a clinical report.. J Prosthet Dent. 2011; 106(6): 355-358.