Ataxia

Features

• Autosomal dominant ataxias many of which are trinucleotide repeat disorders,
◦ Demonstrate anticipation
◦ Tend to present in the third and fourth decades.
• S&S
◦ Pyramidal signs such as hyperreflexia and spasticity.
◦ Sensory neuropathy is common,
◦ Dystonia, chorea, or cognitive decline.
• Machado-Joseph disease (SCA3) is one of the commonest and ataxia, hyperreflexia, nystagmus/ophthalmoplegia, and dysarthria develop early in the disease and may also show a levodopa-responsive rest tremor

Fragile X-associated tremor ataxia syndrome (FXTAS) is characterized by the presence of a permutation for fragile X syndrome (CGG triplet repeat in insufficient number to cause the full fragile X syndrome).
It is accompanied by intention tremor, gait ataxia, rigidity, bradykinesia, polyneuropathy, and autonomic manifestations

Unusual hematologic findings + ataxia and are often diagnostic.
• Genetic
◦ Autosomal recessive.
◦ Mutation in gene that encodes microsomal transfer protein (MTP) → Chylomicrons, VLDL, LDL absent (Deficiency in apo B48– and apo B100–containing lipoproteins)
• Usually becomes symptomatic during early childhood.
• Investigation
◦ Intestinal biopsy shows lipid-laden enterocytes (arrow in A).
◦ Peripheral blood smear: acanthocytes,
◦ Plasma lipid profile will reveal a very low cholesterol and triglyceride content.
• S&S
◦ Affected infants present with severe fat malabsorption, steatorrhea, failure to thrive.
◦ Later manifestations include
▪ Retinitis pigmentosa (Vit A & E deficiency)
▪ Spinocerebellar degeneration (Vit E deficiency)
▪ Progressive ataxia (Vit E deficiency)
▪ Acanthocytosis (Vit E deficiency)
◦ The initial complaints are similar to the spinocerebellar signs of Friedreich disease.
▪ Ataxia, areflexia, distal muscle atrophy, intestinal symptoms, loss of vibratory sense;
◦ Retinitis pigmentosa/steatorrhea (fat malabsorption) resulting in vitamin A, D, E, K deficiency;
◦ Deficits accumulate over the course of years
• Treatment
◦ Restriction of long-chain fatty acids, large doses of oral vitamin E

Eight forms of episodic ataxia have been thus far been described (EA1 to EA7 and DYT9), all caused by ion channel mutations.
• EA1 and EA2 are of particular interest because they arise from defects in the same chromosome (chromosome 19) but have different phenotypes.
◦ EA1 is caused by mutations in a potassium channel gene
▪ EA1 is characterized by kinesigenic attacks of myokymia and ataxia that last seconds to minutes.
▪ Symptoms of EA1 abate over time,
◦ EA2 by mutations in a voltage-dependent calcium channel.
▪ EA2 is characterized by non-kinesigenic episodes of ataxia and vertigo that can last days.
▪ Symptoms of EA2 is a lifetime affliction