Objective: Case report

Background: Ataxia with vitamin E deficiency (AVED) is an autosomal recessive disorder caused by mutations in the gene encoding the α-tocopherol transport protein (αTTPA). Such mutations give rise to a loss of gene function leading to low systemic levels of vitamin E resulting in a cerebellar syndrome, although it may associate extraneurological symptoms.

Method: A 27 years old woman initiates a progressive ataxia and dysarthria at 8 years of age. Family history elucidated a paternal grandmother with a non specific impairment of gait, consanguineous parents (cousins) and father affected by hypertrophic cardiomyopathy. The inspection showed kyphoscoliosis and cavus feet. Neurological examination evidenced evoked nystagmus at extreme bilateral gaze as well as a slight increased latency in saccades. There were global hypotonia, bilateral dysmetria in finger-nose and heel-knee maneuvers, disdiadochokinesia, truncal ataxia with positive Romberg, unstable wide-based gait and difficult tandem. Generalized areflexia together with bilateral extensor plantar reflex and mild hypopalestasia were present. Cranial MRI revealed platibasia. Electromyography detected an alteration of posterior cordonal pathway and pyramidal pathway for both upper and lower extremities. Transthoracic echocardiogram was normal.

Results: Friedreich’s ataxia was the first diagnostic option. However the frataxin gene analysis confirmed two alleles without evidence of expansion. Laboratory study proved vitamin E deficiency (α-tocopherol concentration: 4.72 μmol/L). Other laboratory data including celiac antibodies, fasting lipids, copper and ceruloplasmin was normal. AVED was confirmed genetically being the patient an homozygous carrier of the pathogenic change c.513_514insTT. Both parents are heterozygous carriers. The patient began treatment with high doses of vitamin E, although vitamin E level did not improved after 1 year follow-up.

Conclusion: The most frequently described mutation is 744delA (especially in North Africa) and secondly is 513insTT. This variant has been described in patients of northern European, Dutch, German, Danish and Italian origin associated with cerebellar symptoms. The presence of myocardiopathy has been described in different series of cases with a prevalence between 19-31% mainly as a left ventricular hypertrophy, dilated cardiomyopathy or electrocardiographic alterations. However, the presence of cardiopathy in heterozygous carriers has not been previously described.

References: 1-Naima Marzouki, Ali Benomar, Mohamed Yahyaoui, Nezha Birouk, Mohamed Elouazzani, Taib Chkili, Mohamed Benlemlih, Vitamin E deficiency ataxia with (744 del A) mutation on α-TTP gene: genetic and clinical peculiarities in Moroccan patients, European Journal of Medical Genetics, Volume 48, Issue 1, 2005, Pages 21-28. 2-Mariotti C, Gellera C, Rimoldi M, Mineri R, Uziel G, Zorzi G, et al. Ataxia with isolated vitamin E deficiency: neurological phenotype, clinicalfollow-up and novel mutations in TTPA gene in Italian families. Neurol Sci 2004; 25: 130–7. 3-Ghada El Euch-Fayache, Yosr Bouhlal, Rim Amouri, Moncef Feki, Fayçal Hentati; Molecular, clinical and peripheral neuropathy study of Tunisian patients with ataxia with vitamin E deficiency, Brain, Volume 137, Issue 2, 1 February 2014, Pages 402–410. 4-May Cabrero, Hernandez Cristobal J, Cantarero Duque S, Martinez Delagado B, Urisote Azcorra M, Robledo Batanero M, et al. Distribution of dominant hereditary ataxias and Friedreich‘s ataxias in the Spanish population. Med Clin (Barc) 2000; 115: 121–5. 5-Anheim M, Fleury M, Monga B, Laugel V, Chaigne D, Rodier G, et al. Epidemiological, clinical, paraclinical and molecular study of a cohort of 102 patients affected with autosomal recessive progressive cerebellar ataxia from Alsace, Eastern France: implications for clinical management. Neurogenetics 2010; 11: 1–12. 6-Angelini L, Erba A, Mariotti C, Gellera C, Ciano C, Nardocci N. Myoclonic dystonia as unique presentation of isolated vitamin E deficiency in a young patient. Mov Disord 2002; 17: 612–4.

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