Efficacious vitamin E treatment in a child with ataxia with isolated vitamin E deficiency

Vitamin E deficiency can cause a progressive spinocerebellar ataxia similar to Friedreich ataxia phenotype [2, 3]. Differential diagnosis between the two forms is based on serum level of vitamin E and is very important for prognosis because in patients with ataxia with isolated vitamin E deficiency (AVED) vitamin E supplementation allows a stabilization of the neurological conditions [3, 6] and may lead to clinical improvement [4]. We report the case of a young patient with AVED with a complete regression of ataxia after early and long-term vitamin E oral supplementation. Our case strongly suggests early recognition and treatment of vitamin E deficiency to improve disease outcome. AVED (OMIM #277460) is a rare autosomal recessive neurodegenerative disease caused by mutations in the αtocopherol transfer protein (TTPA) gene, which maps to locus 8q13.1-q13.3 on chromosome 8 [3]. The deficit reduces the capacity to incorporate α-tocopherol (the most biologically active form of vitamin E) into very low density lipoproteins secreted by the liver and therefore into plasma and tissues [1]; it affects particularly the nervous system, where neurons are more vulnerable to free-radical damage [5]. The disease was characterized clinically and the defective gene localized to proximal chromosome 8q by Ben Hamida et al. in 1993 [2]. Neurological findings include spinocerebellar degeneration and mild to moderate axonal sensory neuropathy (less severe than in Freidreich ataxia), with clinical picture of ataxia, areflexia, dysarthria, and impaired proprioception. AVED should be differentiated from other syndromes with vitamin E deficiency, which can be caused by intestinal and liver diseases, malabsorption or malnutrition [1]. An 8-year-old girl came to our attention for progressive ataxia since the age of 3 years. She was the only child of healthy consanguineous parents (3rd degree) with a family history of a not defined ataxia in the father’s line. Neurological examination disclosed spinocerebellar degeneration with clinical features of important trunkal ataxia, head tremor, dysmetria, areflexia, bilateral Babinski sign, pes cavus with retraction of Achilles tendon on left the side. Tests for cholestatic liver disease, fat malabsorption and abetalipoproteinemia showed no pathologic alterations. Brain and spine magnetic resonance imaging, fundus examination, electroencephalogram, electrocardiogram, as well as motor conduction velocity (MCV) on peroneal and median nerves resulted unrevealing. Alphafetoprotein (to rule out Ataxia-Telangiectasia) and molecular DNA analysis for Friedereich ataxia were both negative. Sensory conduction velocity (SCV) on sural and median nerves were suggestive of axonal sensory neuropathy and somatosensory evoked potentials (SEP) showed the alteration of bilateral somatosensory conduction. Alpha-tocopherol level was below the sensitivity of the test (normal values 0.5–2.0 mg/dl) and thus high-dose vitamin E supplementation was given at the dosage of 1200– 1500 mg/day until the serum concentration raised to 1.23 mg/dL. DNA analysis for the detection of the two most common mutations of the α-TTP gene in patients from Mediterranean population [6] showed homozygous 744delA mutation. After only six months we witnessed complete resolution of trunkal and limb ataxia as well as SCVand SEP normalization. Deep tendon reflexes remained abolished and the foot deformity persisted requiring surgical correction. We want to highlight the importance of the assay of vitamin E serum levels in Friedreich-like ataxia. In our case the truncating homozygous 744delA mutation caused the complete abolishment of α-TTP synthesis with a severe and early phenotype of the disease [1, 4]. However, early and high-dose oral supplementation could lead to complete L. Doria-Lamba (*) . E. De Grandis . E. Cristiani . I. Fiocchi . L. Montaldi . P. Grosso Operative Unit of Child Neuropsychiatry, Department of Neurosciences, Ophthalmology and Genetics, G Gaslini Institute, University of Genoa, L.go Gaslini 5, 16148 Genoa, Italy e-mail: lauradoria@ospedale-gaslini.ge.it Tel.: +39-010-5636702 Fax: +39-010-381303