Adult-onset spinocerebellar syndrome with idiopathic vitamin E deficiency

A 62-year-old man and his maternal uncle had a selective vitamin E deficiency without generalized fat malabsorption. A progressive neurological disorder comprising ataxia, areflexia, and loss of proprioception developed in their sixth and seventh decades. The vitamin E deficiency is thought to be due to abnormally accelerated utilization, excretion, or degradation of the vitamin. This adult-onset spinocerebellar syndrome is due to vitamin E deficiency not caused by malabsorption.     

Vitamin E deficiency in acquired fat malabsorption

Summary Thirteen patients with adult-onset vitamin E deficiency due to fat malabsorption were investigated clinically and electrophysiologically. These patients had slightly or moderately decreased serum vitamin E (1.7–4.8 g/ml, normal <6.0) or vitamin E/cholesterol ratio (0.21–0.31 mg/g, normal <0.35). Only one patient had typical neurological manifestations of vitamin E deficiency, which improved with supplementary vitamin E. The pathological findings in this patient were also compatible with vitamin E deficiency. This patient had poorly controlled diabetes mellitus due to advanced chronic pancreatitis. Reviewing previously reported cases of vitamin E deficiency with diabetes mellitus in chronic pancreatitis, the duration of deficiency until the onset of symptoms was shorter than in those cases without complications. Although adult patients with early, slight deficiency of vitamin E are generally asymptomatic, patients with diabetes mellitus tend to have early neurological symptoms. The vitamin E tolerance test should be used, because even in some patients with vitamin E deficiency due to malabsorption, the deficiency can be overcome by large oral doses of vitamin E.     

Vitamin E deficiency ataxia associated with adenoma

Vitamin E is one of the most important lipid-soluble antioxidant nutrient. Severe vitamin E deficiency (VED) can have a profound effect on the central nervous system. VED causes ataxia and peripheral neuropathy that resembles Friedreich's ataxia. We report here a patient presenting this syndrome, but also a prolactin and FSH adenoma. Both the neurological syndromes and the adenoma regressed after treatment with alpha-tocopherol. Although, the presence of the prolactinoma in this patient may not be related to his vitamin E deficiency, alpha-tocopherol treatment seems to be beneficial and might usefully be tested in patients with hypophyseal secreting other forms of adenoma.     

Reversible visual evoked potential abnormalities in vitamin E deficiency

A patient with cystic fibrosis and cirrhosis developed a progressive neurological syndrome associated with ataxia, proximal weakness, and ophthalmoplegia. Profound deficiencies of vitamins A, D, and E were present. Visual acuity and results of retinal funduscopy were normal. The pattern reversal visual evoked potential was initially abnormal (P100 latency, 136 and 130 ms from left and right eyes, respectively) but became normal (less than 3 standard deviations from mean control P100 latency) over a two-month period when vitamin E was administered. This case documents a potentially reversible visual evoked potential abnormality in a visually asymptomatic patient with vitamin E deficiency.     

Visual and somatosensory evoked potentials in vitamin E deficiency with cystic fibrosis

Patients with cystic fibrosis (CF) and pancreatic malabsorption frequently have vitamin E deficiency. Affected patients may develop spinocerebellar degeneration with dysarthria, ataxia, proximal weakness, proprioceptive loss and areflexia. Of a highly selected group of 10 patients with vitamin E levels below 5 micrograms/ml (normal 5-20 micrograms/ml), 7 had abnormal neurological examinations, predominantly affecting vibration and joint position perception with some severely affected patients manifesting diminished visual acuity, tremor, ataxia and diffuse weakness. Evoked potential studies showed marked abnormalities in 3 patients, demonstrating deficits in the optic pathways and in the cervical cord dorsal column pathways. Evoked potential studies may supplement careful neurological examination in patients with CF before and after supplementation with vitamin E to evaluate their progression and response to treatment.     

Association between genetic polymorphism of angiotensin-converting enzyme gene and Parkinson's disease

Fifteen Moroccan families with a phenotype resembling Friedreich Ataxia (FA) were studied. Seven families (13 patients) had the 744 del A mutation in the alpha-tocopherol transfer protein (alpha-TTP) gene, characteristic of ataxia with vitamin E deficiency (AVED). The other eight families (16 patients) had GAA expansions in the first intron of the frataxin gene. The clinical differences between the two groups differed. AVED caused by the 744 del A could be distinguished by head titubation, lower frequency of the neuropathy and slower disease progression, decreased visual activity and retinitis pigmentosa, which has also been associated with a His(101) Gln missense mutation in the alpha-TTP gene. The neurological disorder associated with vitamin E deficiency can be improved by the alpha-tocopherol treatment.     

A sequential study of visual evoked potential in patients with vitamin B12 deficiency neurological syndrome.

OBJECTIVE: Visual pathways are vulnerable to vitamin B(12) deficiency but there is paucity of studies evaluating visual evoked potential (VEP) changes following vitamin B(12) supplementation. Our aim was to evaluate the visual evoked potential changes in patients with vitamin B(12) deficiency neurological syndrome and their changes after vitamin B(12) therapy. METHODS: Seventeen patients with vitamin B(12) deficiency neurological syndromes diagnosed on the basis of megaloblastic bone marrow or low serum vitamin B(12) level or both were subjected to testing of visual acuity, field of vision, colour vision and neurological examination. Cranial magnetic resonance imaging was done in 9 patients and pattern reversal VEP was carried out on admission. P(100) latency and amplitude were measured. Visual function and VEP studies were repeated at 3 and 6 months after vitamin B(12) therapy. RESULTS: The patients' age ranged between 17 and 69 years; 7 were females and 16 were lactovegetarians. The duration of symptoms ranged between 10 days and 10 years. Visual acuity, colour vision, field of vision and fundus oculi were normal. VEP revealed prolongation of P(100) latency in 10 patients (17 eyes) which was mild in 2, moderate in 10 and marked in 5 eyes. Six months after treatment, P(100) latency improved to normal in all except 4 eyes. VEP abnormality was related to duration of illness and antiparietal cell antibodies. CONCLUSIONS: VEP is frequently prolonged in patients with vitamin B(12) deficiency neurological syndrome although asymptomatic. It usually returns to normal after treatment.     

Treatment of neurological complication due to postgastrectomy vitamin E deficiency]

Although postgastrectomy vitamin E deficiency rarely occurs, it can cause neuromuscular disorder such as neuropathy, myopathy and cerebellar ataxia. We encounter a lot of cases whose serum vitamin E level were decreased after gastrectomy. We evaluated the oral vitamin E intake as a therapy to these cases. The subjects of this study were 11 gastrectomized patients (8 patients had total gastrectomy, 2 subtotal gastrtectomy, 1 partial gastrectomy) with decreased vitamin E. 10 patients had neurological complications such as dizziness, dysesthesia, truncal ataxia. Serum vitamin E increased to normal level in 10 patients and neurological disturbances were improved in 9 patients. The minimum requirement of oral vitamin E intake was 150 mg a day for normalization of serum vitamin E, on the other hand, it decreased with 150 mg intake in some patients. Their serum level increased with 300 mg. We suggest that it is important to check serum vitamin E in gastrectomized patients and oral vitamin E should be supplied over 300 mg for the therapy with vitamin E deficiency.     

Ataxia with vitamin E deficiency and severe dystonia: report of a case

Mutation of the gene for alpha-tocopherol transfer protein causes ataxia with isolated vitamin E deficiency, a disorder usually stabilized or improved after vitamin E supplementation. Dystonia has rarely been described in ataxia with isolated vitamin E deficiency (AVED) patients. We present the case of a young boy with AVED, whose neurological and extra-neurological cardinal symptoms of the disease improved after vitamin E supplementation but who progressively developed generalized dystonia.     

A case of various neurological deficits caused by multi-vitamin deficiency associated with malabsorption syndrome after pancreatomy and small bowel resection]

A 34-year-old woman presented with walking difficulty and pain in the legs 3 years after several abdominal operations for pancreatic cancer and intestinal obstruction thereafter. Corneal erosion, loss of deep sensation in the legs, polyneuropathy, myopathy, and memory disturbance were recognized. Deficiency of multiple vitamins (A, B1, B6, D, E, K) was found. The diagnoses were vitamin A-deficient corneal erosion, vitamin K-deficient bleeding abnormality (asymptomatic), and the neurological deficits caused by vitamin E, B1, B6 and D deficiency. Although the vitamin supplement started 2 years after the onset of the neurological disease, both clinical and electrophysiological recovery was seen. She was unable to walk on admission, but became able to walk after vitamin E supplement. To our knowledge, this is the first report showing multi-vitamin deficiency causing extensive neurological, ophthalmological, and hematological deficits. Recognition of this condition would prevent the progression of potentially irreversible neurological disorders in patients with malabsorption syndrome after extensive abdominal surgery.     

A study of the relationship between neurological function and serum vitamin E concentrations in patients with cystic fibrosis.

A patient with cystic fibrosis and undetectable serum vitamin E concentrations is described who developed a progressive spinocerebellar syndrome and pigmentary retinopathy with abnormal somatosensory and visual evoked potentials (SSEPs and VEPs). In order to assess the relationship between neurological function and serum vitamin E concentrations in cystic fibrosis, 29 unselected patients who had no neurological symptoms were examined neurologically. Ten were randomly selected for neurophysiological assessment by recording SSEPs and VEPs. Electroretinograms (ERGs) were also performed in five cases. The findings were correlated with serum vitamin E concentrations which were unknown to the neurological investigators prior to completion of the study. Only one patient had definite reflex and sensory abnormalities, and the remaining 28 were clinically normal. The ERG was abnormal in two cases, one of whom had abnormal VEPs. SSEPs were normal in all 10 cases. Twenty six patients had serum vitamin E concentrations below the normal range. In two of the three patients who had definite neurological or electrophysiological abnormalities serum vitamin E concentrations were below the median value for the whole group.     

Isolated vitamin E deficiency

Since the detection of vitamin E in 1922, nearly 50 years passed until the recognition that there is a pathogenic vitamin E deficiency in humans. Such a deficiency can be found mostly in a disturbed resorption or transport of the vitamin (mucoviscidosis, chronic cholestasis, abetalipoproteinaemia) and leads typically to a progredient spinocerebellar ataxia in combination with a polyneuropathy. Substitution of the vitamin may hinder a further progression or even lead to an amelioration of the symptoms. Prophylactic treatment in abetalipoproteinaemia prevents the otherwise unavoidable neurological deficits. Isolated vitamin E deficiency is a rare syndrome and the causes are still obscure. We observed a 26 year old male patient with such a isolated vitamin E deficiency who was hitherto thought to suffer from Friedreich's ataxia. The clinical feature showed in addition to the "classical" symptoms of vitamin E deficiency cranial nerve involvement, perioral dystonia and pyramidal signs. Histologically (M. gastrocnemius) we saw the described typical but not specific changes (neurogenic atrophy, phosphatase-positive vacuoles with myelin bodies, cores). An oral vitamin E resorption test yielded a very shortened serum half life. These results support the hypothesis that in the pathophysiology of isolated vitamin E deficiency malelimination plays an important role in addition the known malresorptions models.     

Ataxia with isolated vitamin E deficiency presenting as mutation negative Friedreich's ataxia

Ataxia with vitamin E deficiency is an autosomal recessivecondition associated with a defect in the α-tocopherol transfer protein. Clinically it manifests as a progressive ataxia with aphenotype resembling that of Friedreich's ataxia. There is some evidence that progression of neurological symptoms is prevented byvitamin E therapy. A patient is described who was given a clinical diagnosis of Friedreich's ataxia. Molecular genetic analysis showed the absence of the frataxin gene expansion. Subsequent vitamin E assayshowed deficiency and a diagnosis of ataxia with vitamin E deficiencywas made. It is recommended that all patients with ataxia of unknowncause should have vitamin E deficiency excluded. When a diagnosis ofFriedreich's ataxia is considered patients should have frataxinanalysis in addition. Further, neurologists should be aware thatataxia with vitamin E deficiency may present as "mutationnegative" Friedreich's ataxia.

     

Cerebellar syndrome in adult celiac disease with vitamin E deficiency

We studied a woman with adult onset celiac disease complicated by a cerebellar syndrome that progressed despite the resolution of the malabsorption symptoms with a gluten free diet. The patient presented vitamin E deficiency and the cerebellar symptoms improved with vitamin E therapy. This case supports the possible role of this deficiency in the development of the neurological complications of celiac disease.     

Spinocerebellar degeneration secondary to chronic intestinal malabsorption: A vitamin E deficiency syndrome

Two adults are described who developed a progressive neurological disorder more than 20 years after the onset of chronic fat malabsorption. The clinical features included dysarthria, cerebellar ataxia, and prominent proprioceptive loss with depressed or absent tendon reflexes. Serum vitamin E was undetectable in both cases. One patient improved clinically and electrophysiologically after oral therapy with vitamin E. The findings in these patients were similar to those in others recently reported with vitamin E deficiency associated with biliary atresia. Electrophysiological observations suggested that the human deficiency state parallels that found neuropathologically in vitamin E-deficient animals.     

A longitudinal study of somatosensory, brainstem auditory and peripheral sensory-motor conduction during vitamin E deficiency in the rat

A severe deficiency of vitamin E causes a characteristic neurological syndrome in man and experimental animals. In this study a number of electrophysiological modalities in vitamin E deficient and control rats have been investigated over a period of one year to define the time of onset and severity of the abnormalities associated with vitamin E deficiency in the rat. The mean velocities (n = 10) of the sensory evoked potentials were slower at all time points in the vitamin E deficient rats, with the central conduction velocities being more severely affected than the peripheral. Central conduction velocities, following both tibial and median nerve stimulation, were significantly delayed (P less than 0.005) after 8 months of deficiency. Differences in peripheral conduction following tibial stimulation became significantly delayed (P less than 0.005) after 11 months of deficiency. There were no significant differences in the brainstem auditory evoked potentials or peripheral sensory motor responses between the vitamin E deficient and control rats over the 1 year period. These results in the rat are essentially similar to those previously reported in vitamin E deficient man.     

Neurological involvement in hereditary transcobalamin II deficiency.

A case of hereditary transcobalamin II deficiency with neurological involvement is described. The patient presented in early infancy with megaloblastic anaemia and was treated with folinic acid from 6 weeks of age. The diagnosis of transcobalamin II deficiency was not made until he was 2 years old when he showed severely retarded intellectual development, ataxia and pyramidal deficit in the limbs. Following treatment with hydroxocobalamin, his condition has slowly improved but he has remained with a severe neurological deficit. The consequences of vitamin B12 deficiency on neurological development in infancy are discussed.     

Reversible inflammatory and vacuolar myopathy with vitamin E deficiency in celiac disease

We report a patient with late-onset celiac disease and neurological manifestations including myopathy, polyneuropathy, and ataxia. Laboratory investigations showed anti-gliadin antibodies and severe vitamin E deficiency. Muscle biopsy revealed inflammatory infiltrates and rimmed vacuoles, similar to those found in inclusion-body myositis. A gluten-free diet and vitamin E supplementation reversed both the clinical neurological manifestations and the abnormalities in the muscle biopsy. Anti-gliadin antibodies were no longer present. This case illustrates the spectrum of neurological complications of celiac disease and documents the occurrence of reversible pathology resembling inclusion-body myopathy in the muscle.     

Friedreich-like ataxia with retinitis pigmentosa caused by the His101Gln mutation of the α-Tocopherol transfer protein gene

The α-tocopherol transfer protein (α-TTP) is a cytosolic liver protein that is presumed to function in the intracellular transport of α-tocopherol, the most biologically active form of vitamin E. We studied 4 unrelated patients with autosomal recessive Friedreich-like ataxia who had isolated vitamin E deficiency. A point mutation was identified in all of them at position 101 of the gene for α-TTP, where histidine (CAT) was replaced with glutamine (CAG). Three of the 4 patients developed retinitis pigmentosa subsequent to the onset of ataxia. Neurological symptoms included ataxia, dysarthria, hyporeflexia, and decreased proprioceptive and vibratory sensations. Electrophysiological and pathological examinations showed that the cardinal sites affected were the central axons of dorsal root ganglion cells and the retina, with minor involvement of the peripheral sensory nerve, optic nerve, and pyramidal tract. The vitamin E tolerance test performed showed that the absorption of vitamin E was normal but that its decrease from the serum was accelerated. Oral administration of vitamin E appeared to halt the progression of visual and neurological symptoms. We propose a new treatable syndrome of Friedreich-like ataxia and retinitis pigmentosa caused by a defect in the α-TTP gene.     

Ataxia with isolated vitamin E deficiency in four siblings

We describe 4 siblings of a consanguineous Bedouin family with Friedreich ataxia phenotype in whom low serum vitamin E levels without other indicators of fat malabsorption were detected. Although age of onset and some of the clinical features were alike in all 4 patients, the electrophysiological parameters were markedly abnormal in 2, but normal in the other 2. Erythrocytes revealed both membranous and intracellular evidence of oxidative damage. The mutations described in other families with ataxia with isolated vitamin E deficiency were not detectable, nor was an abnormal single-stranded conformation polymorphism pattern apparent in the three exons at the 3′ region of the gene. Vitamin E administration in pharmacological doses improved the neurological condition in 2 patients and also corrected some of the patients' erythrocyte cell abnormalities. The finding of vitamin E deficiency in other cases of Friedreich ataxia phenotype may allow treatment at an early stage of the disease, when large dose Vitamin E therapy may reverse the neurological lesions.