There are several genetic disorders such as Friedreich and non-Friedreich ataxias that can present with ataxia among children.
Friedreich ataxia is an autosomal recessive triple repeat disease with a number of components. Symptoms are present by age 10 years in about half of those affected, and almost all have symptoms by the early 20s.
Friedreich ataxia occurs secondary to a mutation of the mitochondrial protein, frataxin, located on chromosome 9. Spinal cord degeneration occurs in three distinct regions: (1) posterior columns and dorsal root ganglia, (2) corticospinal tracts, and (3) spinocerebellar tracts. The sensory neuropathy associated with Friedreich ataxia occurs because of progressive degeneration of the dorsal ganglion and axon. There is some associated secondary demyelination.
The primary feature of Friedreich ataxia is gait ataxia. This ataxia is progressive and typically leads to the need for a wheelchair. There is associated peripheral neuropathy, dysarthria, and cardiomyopathy (in 50% of cases). Hearing loss and optic atrophy occur only rarely. Most patients are unable to walk by age 30 years.
There is no specific treatment for Friedreich ataxia. The patient is at risk of falling, and appropriate safety measures should be taken. Furthermore, the patient's feet should be checked on a daily basis for cuts or blisters that might otherwise go unnoticed because of the sensory loss.
There are a number of distinct and unrelated diseases that have phenotypes similar to Friedreich ataxia.
Ataxia with Vitamin E Deficiency (Aved)
Ataxia with vitamin E deficiency arises secondary to abnormalities in vitamin E absorption or metabolism. AVED can result in a syndrome clinically indistinguishable from Friedreich ataxia. AVED is an autosomal recessive disease with a mutation in the gene encoding for alpha-tocopherol transfer protein (alpha-TTP), and results in low or undetectable levels of vitamin E without associated fat malabsorption.
Abetalipoproteinemia (Bassen-Kornzweig Syndrome)
Abetalipoproteinemia is a rare autosomal recessive disorder of lipoprotein metabolism. There is malabsorption of vitamin E. There is an absence of apolipoprotein B-containing proteins (chylomicrons, LDL, VLDL), and diagnostic studies can help in distinguishing this disorder from Friedreich ataxia, including a low serum cholesterol level, acanthocytosis on peripheral blood smear, and an abnormal serum protein electrophoresis. Furthermore the presence of retinopathy distinguishes the disorder from Friedreich ataxia.
Acquired Vitamin E Deficiency
Acquired vitamin E deficiency can be associated with severe fat malabsorption in diseases such as cystic fibrosis, cholestatic liver disease, celiac disease, and short bowel syndrome. While there may be an ataxia clinically similar to Friedreich ataxia, there are typically symptoms associated with the primary disease that guide diagnosis.
Early-Onset Cerebellar Ataxia with Retained Reflexes (Eoca)
The early-onset cerebellar ataxias are a heterogeneous group of disorders, most of which are autosomal recessive. The EOCA disorders have a childhood onset resembling Friedreich ataxia but with retained reflexes. There may be spasticity, but the diabetes, cardiac disease, and skeletal deformities are absent. The Friedreich ataxia triplet repeat test is negative and the prognosis is better than with Friedreich ataxia.
Progressive Ataxia Associated with Biochemical Abnormalities
Multiple inherited diseases can cause progressive ataxia, including ceroid lipofuscinosis, cholestanolosis, ataxia-telangiectasia, xeroderma pigmentosum, Cockayne syndrome, GM-2 gangliosidosis, adrenoleukodystrophy, metachromatic leukodystrophy, mitochondrial diseases (MERRF, KSS, NARP), sialidosis, and Niemann-Pick and sphingomyelin storage disorders.
Ataxia Telangiectasia (Louis-Bar Syndrome)
Ataxia telangiectasia is an autosomal recessive disease with a mutation in the ATM gene (leads to defect in DNA repair) on chromosome 11. Symptoms of ataxia telangiectasia typically begin during infancy. There is progressive truncal ataxia, usually resulting in the patient being wheelchair-bound by age 12 years. The hallmark oculocutaneous telangiectasias usually appear between ages 3 and 5 years, well after the onset of ataxia. Other symptoms include dysarthria, nystagmus, oculomotor dyspraxia, dystonia, athetosis, myoclonic jerks, polyneuropathy, and cognitive dysfunction.
Diagnostic studies reveal elevated AFP and CEA levels (alpha-fetoprotein and carcinoembryonic antigen), and decreased or absent IgA levels. Fibroblasts can be screened for increased x-ray sensitivity and radioresistant DNA synthesis. The associated immunodeficiency leads to recurrent respiratory infections. Ataxia telangiectasia is also associated with cancer, typically leukemias and lymphomas. The average age of death is 20 years and is usually from infection or neoplasm.
Progressive Myoclonic Ataxias
The progressive myoclonic ataxias are a heterogenous group of childhood disorders associated with progressive cerebellar ataxia and action myoclonus. Most of these disorders are due to mitochondrial disorders (MERRF, KSS, NARP). Rare cases of polyQ disease and dentatorubral-pallidoluysian atrophy (DRPLA) have juvenile onset.