autosomal recessive

Infants may appear normal at birth but within a few months develop signs of developmental stagnation with onset of tonic-clonic seizures.  Irritability, poor feeding, vomiting and failure to thrive are important features.  Generalized hypotonia is evident but lower limb deep tendon reflexes may be present.  Normal developmental milestones are never achieved and patients are unresponsive to their environment.  Older individuals develop non-purposeful choreothetoid movements.  The EEG shows multifocal epileptiform discharges and brain MRIs show diffuse atrophy in older patients.

Hypo- and hyperpigmented skin macules in a 'salt and pepper' pattern, have been described.  These vary from 2-5 mm in size and are located primarily on the extremities.  These are found among children older than 3 years of age and some parents have reported that the hyperpigmentation may decrease after many years.  No such lesions were found in mucosal tissue.        

Friedreich ataxia is a progressive neurodegenerative disorder with onset before puberty.  The spinocerebellar tracts, dorsal columns, pyramidal tracts, cerebellum, medulla, and optic radiation, may all be involved.  The outstanding symptom is ataxia with impairment of gait and weakness in the limbs.  Muscle weakness, extensor plantar responses, and absent lower limb reflexes are usually present.  Dysarthria is usually notable.  Sensory signs include impairment of position and vibratory senses.  'Twitching' in limbs and digits is often noted and 'restless leg syndrome' is common.

Secondary changes include pes cavus, scoliosis, and hammer toe.  Cardiac disease is frequently present and heart failure is the most common cause of death.  Most patients have hypertrophic cardiomyopathy with characteristic EKG changes and some have subaortic stenosis as part of the hypertrophied myocardium.  Diabetes mellitus is present in 20-25%.  Some hearing loss occurs in more than 10% of individuals.

Most patients require a wheelchair within 15 years of disease onset and the mean age of death is about 36 years.

Rare patients with a later onset of FRDA retain lower limb deep tendon reflexes.

This is a congenital disorder with cerebral ataxia (limb and truncal), spastic paraparesis (increased lower limb tone with brisk knee jerks and extensor plantar responses), cerebellar and spastic dysarthria, learning difficulties and emotional lability as prominent features.  The onset of both speech and mobility are delayed.  Older individuals have slow and spastic tongue movements with brisk jaw jerks, and increased tone in the upper limbs.  Motor function progressively declines although even older individuals in the third decade of life remain mobile albeit with an increasingly spastic and ataxic gait, and require only minimal assistance with self-care.  Children in grade school require special education accommodations but there is no obvious deterioration in intellectual function as they mature.

Psychomotor development is initially normal but signs of delay are usually present during the first year of life.  Patients may be able to walk but only with support.  Pyramidal and cerebellar dysfunction, muscle weakness and wasting, dysarthria, truncal hypotonia, intention tremor, and spasticity are evident during the first decade.  Some have seizures.  Cognitive impairment ranges from mild to moderate.  Most patients become wheelchair-bound late in the first decade of life and some do not survive beyond childhood.

Hypomyelination and mild axonal loss may be seen in peripheral nerve biopsies while neuroimaging shows evidence of diffuse and progressive cerebral white matter atrophy.

This is a disorder of glycosylation important to the formation of glycoproteins and glycolipids.  Neurological signs such as tremor, clonus, and muscle fasiculations may be seen soon after birth.  Other neurological abnormalities eventually include psychomotor retardation, seizures, mental retardation, hyperexcitabilty, and ataxia.  Failure to thrive and feeding difficulties are evident early.  Progressive microcephaly is a feature.  Liver dysfunction can lead to coagulopathy and hypoproteinemia with hepatomegaly is sometimes present.  Some patients have facial anomalies, inverted nipples, and subcutaneous fat pads.  The MRI may show areas of brain atrophy, ischemia, and focal necrosis.

Longevity is limited with 2 of 3 reported patients dying within 2 years of life.

Early development may seem normal but developmental milestones are usually delayed.  Postnatal microcephaly and growth deficiency with mental retardation and early hypotonia are typical features.  The mental retardation may be severe.  Scoliosis and arachnodactyly have been noted and hypogonadism has been reported.  Speech may not develop and mobility is sometimes limited.

Onset of symptoms may occur at any time from 1.5 years of age to adulthood.  Early psychomotor development may be normal but developmental milestones such as walking and crawling are often delayed.  Patients with a later onset often have a milder course.  Progression is chronic but often episodic with exacerbations following infection and blunt head trauma. Mental stress, even of a relatively minor nature such as fright, may likewise cause a worsening of symptoms.  Such episodes can lead to loss of consciousness or even coma.  Cerebellar ataxia and spasticity are common.  Epilepsy may occur but is uncommon.  Motor function is more severely impaired compared with mental deterioration.  The MRI reveals a diffuse leukoencephalopathy as well as focal and cystic degeneration of white matter which may be present before the onset of symptoms.  Cerebellar atrophy primarily involving the vermis is common.  Behavioral problems, psychiatric symptoms, and even signs of dementia have been reported.  The vast majority of patients have cognitive disabilities and many become severely handicapped and immobile.  Early onset disease in children often leads to death within a few years whereas adults with later onset may live for many years.       

Females with leukoencephalopathy who live to puberty may experience ovarian failure, a condition sometimes called ovarioleukodystrophy.