basal ganglia disease

Mitochondrial Short-Chain Enoyl-CoA Hydratase 1 Deficiency

Clinical Characteristics
Ocular Features: 

The ocular phenotype has not been thoroughly studied.  Nystagmus has been reported in several infants.

Systemic Features: 

Evidence of severe psychomotor retardation is evident at birth or shortly thereafter.  Neonatal hypotonia with a poor suck reflex and episodic apnea is evident.  Spasticity may become evident later.  Brain imaging shows T-weighted hyperintensity areas in the basal ganglia resembling Leigh syndrome lesions.  The corpus callosum appears thin.  Serum and CSF lactate is elevated and decreased activity of the pyruvate dehydrogenase complex is present.

Infants do not achieve normal developmental milestones such as speech or sitting unsupported and several have died early in childhood from cardiorespiratory failure, possibly related to a combined mitochondrial respiratory chain dysfunction.

Genetics

The transmission pattern in several families is consistent with autosomal recessive inheritance.  Compound heterozygous mutations have been found in the ECHS1 gene (10q26.3).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment has been reported.

References
Article Title: 

Pantothenate Kinase-Associated Neurodegeneration

Clinical Characteristics
Ocular Features: 

Clinically evident retinal degeneration is present in a significant number (25-50%) of individuals.  However, when combined with ERG evidence the proportion rises to 68%.  When present it occurs early and one series reported that it is unlikely to appear later if it was not present early in the course of the neurodegeneration.  Some patients have a fleck-like retinopathy.  Optic atrophy may be present in advanced cases.

Systemic Features: 

This is a disorder primarily of the basal ganglia resulting from progressive damage secondary to iron accumulation.  There is an early onset classic form with symptoms of extrapyramidal disease beginning in the first decade of life and rapid progression to loss of ambulation in about 15 years.  Others with atypical disease may not have symptoms until the second or third decades.  Clumsiness, gait disturbance, and difficulty with tasks requiring fine motor coordination are common presenting symptoms.  Motor tics are often seen.  Dysarthria, dystonia, rigidity and corticospinal signs are often present early as well.  Swallowing difficulties may be severe sometimes leading to malnutrition.  Cognitive decline and psychiatric disturbances such as obsessive-compulsive behavior and depression may follow.  Independent ambulation is lost in the majority of patients within one to two decades.    Brain MRIs show an ‘eye of the tiger’ sign with a specific T2- weighted pattern of hyperintensity within the medial globus pallidus and the substantia nigra pars reticulata.

Genetics

Iron accumulation in the basal ganglia resulting from homozygous mutations in the PANK2 gene (20p13-12.3) encoding a pantothenate kinase leads to the classic form of this autosomal recessive disorder. 

This is the most common of several diseases of neurodegeneration with iron accumulation in the brain known collectively as NBIAs.  The group is genetically heterogeneous with many overlapping features.  Mutations in PLA2G6 cause NBIA2A (256600) and NBIA2B (610217) while mutations in a FLT gene cause NBIA3 (606159). The latter does not have apparent eye signs.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Pharmacologic treatment is aimed at alleviation of specific symptoms such as dystonia and spasticity.  Some symptoms may improve with deep brain stimulation.

References
Article Title: 
Subscribe to RSS - basal ganglia disease