Clinical and genetic study of ataxia with vitamin E deficiency: A case report.

BACKGROUND: Ataxia with vitamin E deficiency (AVED) is a type of autosomal recessive cerebellar ataxia. Clinical manifestations include progressive cerebellar ataxia and movement disorders. TTPA gene mutations cause the disease. CASE SUMMARY: We report the case of a 32-year-old woman who presented with progressive cerebellar ataxia, dysarthria, dystonic tremors and a remarkably decreased serum vitamin E concentration. Brain magnetic resonance images showed that her brainstem and cerebellum were within normal limits. Acquired causes of ataxia were excluded. Whole exome sequencing subsequently identified a novel homozygous variant (c.473T>C, p.F158S) of the TPPA gene. Bioinformatic analysis predicted that F185S is harmful to protein function. After supplementing the patient with vitamin E 400 mg three times per day for 2 years, her symptoms remained stable. CONCLUSION: We identified an AVED patient caused by novel mutation in TTPA gene. Our findings widen the known TTPA gene mutation spectrum.

A first description of ataxia with vitamin E deficiency associated with MT-TG gene mutation.

Ataxia with isolated vitamin E deficiency (AVED) is a rare autosomal recessive cerebellar ataxia disorder that is caused by a mutation in the alpha-tocopherol transfer protein gene TTPA, leading to a lower level of serum vitamin E. Although it is almost clinically similar to Friedreich's ataxia, its devastating neurological features can be prevented with appropriate treatment. In this study, we present a patient who was initially diagnosed with Friedreich's ataxia, but was later found to have AVED. Frataxin gene screening revealed the absence of GAA expansion in homozygous or heterozygous state. However, TTPAgene sequencing showed the presence of the c.744delA mutation, leading to a premature stop codon (p.E249fx). In addition, the result of mutational analysis of MT-DNA genes revealed the presence of several variants, including the m.10044A>G mutation in MT-TG gene. Here, we report for the first time the coexistence of both mitochondrial and nuclear genes mutations in AVED.

Retinitis pigmentosa and macular degeneration in a patient with ataxia with isolated vitamin E deficiency with a novel c.717 del C mutation in the TTPA gene.

Ataxia with isolated vitamin E deficiency (AVED) is a neurodegenerative disease caused by a mutation in the α-tocopherol transfer protein gene (TTPA). The clinical features of the disease resemble Friedreich's ataxia. However, AVED is associated with low plasma vitamin E levels, which results in compromised antioxidant function. Dysregulation of this lipid-soluble antioxidant vitamin plays a major role in the neurodegeneration observed in AVED. Some AVED patients experience decreased visual acuity. Retinitis pigmentosa is thought to be the main cause of this visual impairment. Although antioxidant levels are important for the prevention of macular degeneration, there have been no reports of macular degeneration in AVED. Here, we describe a patient with AVED with progressive macular degeneration, who carried a novel truncating mutation-c.717 del C (p.D239EfsX25)-in exon 5 of the TTPA gene. These findings suggest that this newly identified mutation results in severely low serum vitamin E levels, which may be associated with the development of retinitis pigmentosa and macular degeneration.

Hallazgos clínicos y moleculares en una paciente con ataxia por deficiencia de vitamina E, homocigota para la mutación c.205-1G>C en el gen TTPA / Clinical and molecular findings in a patient with ataxia with vitamin E deficiency, homozygous for the c.205-1G>C mutation in the TTPA gene

Introducción. La ataxia por deficiencia de vitamina E es causada por mutaciones en el gen TTPA . Está caracterizada por ataxia, arreflexia, temblor cefálico, pérdida de la propiocepción, Babinsky, disdiadococinesia, retinitis pigmentosa y cardiomiopatía. Caso clínico. Se trató de una paciente del sexo femenino de 11 años, padres consanguíneos, valorada por dolor y parestesias en miembros inferiores, disartria y problemas para escribir y masticar. El examen físico mostró fuerza distal disminuida, hiperreflexia, Babinsky, disminución en la propiocepción, pie cavo bilateral, dismetría, disdiadococinesia y Romberg positivo. El estudio para ataxia de Friedreich resultó normal, aunque presentó bajos niveles de a-tocoferol y se identificó una mutación homocigota c.205-1G>C en el gen TTPA . Se inició tratamiento con vitamina E con lo que mostró mejoría. Conclusiones. Ante la presencia de manifestaciones parecidas a la ataxia de Friedreich se sugiere evaluar niveles plasmáticos de α-tocoferol y realizar estudios genéticos confirmatorios. El tratamiento con vitamina E disminuye los síntomas en los afectados y los presintomáticos no desarrollan manifestaciones del trastorno. Se han reportado pocos casos en Latinoamérica. En esta paciente se encontró una mutación en estado homocigoto fuera de las áreas de mayor prevalencia. Dichos hallazgos clínicos pueden indicar que la mutación c.205-1G>C se asocia con un cuadro severo.

Background. Ataxia with vitamin E deficiency is a disorder caused by mutations in the TTPA gene. Common symptoms include ataxia, areflexia, head titubation, loss of proprioception, Babinsky sign, dysdiadochokinesia, pigmentary retinopathy and cardiomyopathy. Case report. The patient was the first child of consanguineous parents. She presented at 10 years of age due to bilateral lower limb pain and numbness and difficulty in speech, writing and chewing. Physical examination showed dysarthria, diminished distal strength, hyperreflexia, positive Babinsky sign, decreased proprioception, pes cavus, dysmetria, dysdiadochokinesia and positive Romberg sign. Genetic screening for the Friedreich's ataxia gene resulted negative, α-tocopherol levels were low and TTPA gene sequentiation detected the homozygous mutation c.205-1G >C in intron 1. Treatment was initiated with vitamin E, showing improvement of symptoms. Conclusions. The presence of Friedreich's ataxia-like phenotype suggests the need to perform tests of plasma levels of α-tocopherol and the confirmatory genetic test. Treatment with vitamin E decreases symptoms in both affected and presymptomatic individuals. Few patients have been described in America, and our case showed a homozygous mutation outside of high-prevalence areas. Clinical findings of this patient and a previous case would indicate that the c.205-1G>C mutation is associated with severe symptoms.