TTPA gene
Also known as: Ataxia, Friedreich-like, with selective vitamin E deficiency; Vitamin E deficiency, familial isolated; VED; Friedreich-like ataxia
OMIM#277460 https://omim.org/entry/277460
1. The Disease:
A neurodegenerative disease belonging to the inherited cerebellar ataxias mainly characterized by progressive spino-cerebellar ataxia, loss of proprioception, areflexia, and is associated with a marked deficiency in vitamin E.
2. The symptoms:
Ataxia with vitamin E deficiency (AVED) generally manifests in late childhood or early teens between ages five and 15 years. Lack of early signs or symptoms does not exclude the diagnosis.
The first symptoms include progressive ataxia, clumsiness of the hands, loss of proprioception, and areflexia. Other features often observed are difficulty to do alternate muscle movements, and to speak, positive Romberg sign, head titubation, decreased visual acuity, and positive Babinski sign. The phenotype and disease severity vary widely among families with different pathogenic variants; age of onset and disease course are more uniform within a given family, but symptoms and disease severity can vary even among sibs.
3. Actions to take in case of early diagnosis:
Biochemical correlation is recommended with very low levels of E vitamin (alpha-tocoferol) and a normal lipoprotein profile in the absence of known causes of malabsorption.
AVED is a lifelong disease requiring lifetime management and regular follow-up with a Paediatric Neurology Center Management is provided by multidisciplinary team.
Lifelong high-dose oral vitamin E supplementation to bring plasma vitamin E concentrations into the high-normal range; treatment early in the disease process may to some extent reverse ataxia and mental deterioration.
Genetic counselling is highly recommended for family planning and evaluation of at-risk family members such as siblings.