Untangling the Thorns: Advances in the Neuroacanthocytosis Syndromes

Abstract

There have been significant advances in neuroacanthocytosis (NA) syndromes in the past 20 years, however, confusion still exists regarding the precise nature of these disorders and the correct nomenclature. This article seeks to clarify these issues and to summarise the recent literature in the field. The four key NA syndromes are described here–chorea-acanthocytosis, McLeod syndrome, Huntington’s disease-like 2, and pantothenate kinase- associated neurodegeneration. In the first two, acanthocytosis is a frequent, although not invariable, finding; in the second two, it occurs in approximately 10% of patients. Degeneration affecting the basal ganglia is the key neuropathologic finding, thus the clinical presentations can be remarkably similar. The characteristic phenotype comprises a variety of movement disorders, including chorea, dystonia, and parkinsonism, and also psychiatric and cognitive symptoms attributable to basal ganglia dysfunction. The age of onset, inheritance patterns, and ethnic background differ in each condition, providing diagnostic clues. Other investigations, including routine blood testing and neuroimaging can be informative. Genetic diagnosis, if available, provides a definitive diagnosis, and is important for genetic counseling, and hopefully molecular therapies in the future. In this article I provide a historical perspective on each NA syndrome. The first 3 disorders, chorea-acanthocytosis, McLeod syndrome, Huntington’s disease-like 2, are discussed in detail, with a comprehensive review of the literature to date for each, while pantothenate kinase-associated neurodegeneration is presented in summary, as this disorder has recently been reviewed in this journal. Therapy for all of these diseases is, at present, purely symptomatic.

Neuroacanthocytosis in Two Brothers: An Ultra-rare Cause of Movement Disorder

“…Vocal tics consisting of gasping, sighing, whistling, blowing, sucking, and humming occur in most of patients (1,2).…”

“…Generalized tonicclonic or partial complex seizures occur in half of patients; some patients develop epilepsy as their initial clinical manifestation (1,2). In many patients, seizures are found to originate from one or both temporal lobes (1,2). Neuropathy is often subclinical, manifesting with distal muscle wasting, depressed distal deep tendon reflexes, and mild sensory abnormalities, particularly impaired vibration sense (3,4).…”

“…The core neuroacanthocytosis syndromes mainly encompass of the two diseases, choreaacanthocytosis and the McLeod syndrome. Huntington's disease-like 2, and pantothenate kinase-associated neurodegeneration (PKAN) are very rare but these diseases can also be incorporated in this group of syndromes (1,2). Chorea-acanthocytosis is rare, with an estimated around 1000 cases worldwide (2).…”

“…The mean age of onset was 35 years in a systemic review with a broad range from the first to the seventh decade. Initial clinical symptoms can vary widely (1)(2)(3). The main syndrome is a result of an autosomal recessive mutation.…”

“…The main syndrome is a result of an autosomal recessive mutation. However, the other subtypes are X-linked (McLeod type) or autosomal dominant (1). The main differential diagnoses are Wilson disease and Huntington's disease (3).…”