Isolated vitamin E deficiency

A 22-year-old man presented with progressive gait instability, tremor, and dysarthria since childhood. Electrophysiologic studies revealed a sensorimotor polyneuropathy. Laboratory studies documented vitamin E deficiency; however, no gastrointestinal, hepatic, or lipoprotein disorder could be identified. Vitamin E therapy normalized the serum level, but there was no neurologic improvement. Isolated vitamin E deficiency, in the absence of lipid malabsorption, should be considered in the evaluation of children and adults with ataxia and peripheral neuropathy. © 1996 John Wiley & Sons, Inc.     

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 vitamin E deficiency: biochemical effects of malcompliance with vitamin E therapy

To prevent neuronal damage, patients with ataxia with isolated vitamin E deficiency need lifelong supplementation with high doses of vitamin E. Short interruptions of therapy, such as occur in malcompliance, do not lead to clinical symptoms. However, the authors show that even short withdrawals may cause a prolonged decrease of the total radical trapping capacity of plasma; its major contributors, such as urate and sulfhydryl groups, fail to compensate for the missing vitamin E.     

Effect of vitamin E supplementation in patients with ataxia with vitamin E deficiency

Ataxia with vitamin E (Vit E) defciency (AVED) is an autosomal recessive disorder caused by mutations of the alpha tocopherol transfer protein gene. The Friedreich ataxia phenotype is the most frequent clinical presentation. In AVED patients, serum Vit E levels are very low in the absence of intestinal malabsorption. As Vit E is a major antioxidant agent, Vit E deficiency is supposed to be responsible for the pathological process. Twenty-four AVED patients were fully investigated (electromyography, nerve conduction velocity (NVC) studies, somatosensory evoked potentials, cerebral computed tomography scan, sural nerve biopsy, genetic studies) and supplemented with Vit E (800 mg daily) during a 1-year period. Clinical evaluation was mainly based on the Ataxia Rating Scale (ARS) for cerebellar ataxia assessment and serum Vit E levels were monitored. Serum Vit E levels normalized and ARS scores decreased moderately but significantly suggesting clinical improvement. Better results were noted with mean disease duration < or = 15 years. Reflexes remained abolished and posterior column disturbances unchanged. Vitamin E supplementation in AVED patients stabilizes the neurological signs and can lead to mild improvement of cerebellar ataxia, especially in early stages of the disease.     

Ataxia with vitamin E deficiency: update of molecular diagnosis

Ataxia with vitamin E deficiency (AVED) is a rare autosomal recessive neurodegenerative disease, due to mutations in TTPA gene (Arita et al. in Biochem J 306(Pt. 2):437–443, 1995; Hentati et al. in Ann Neurol 39:295–300, 1996), which encodes for α-TTP, a cytosolic liver protein that is presumed to function in the intracellular transport of α-tocopherol. This disease is characterized clinically by symptoms with often striking resemblance to those of Friedreich ataxia. The neurological symptoms include ataxia, dysarthria, hyporeflexia, and decreased vibration sense, sometimes associated with cardiomyopathy and retinitis pigmentosa (Mariotti et al. in Neurol Sci 25:130–137, 2004). Vitamin E supplementation improves symptoms and prevents disease progress (Doria-Lamba et al. in Eur J Pediatr 165(7):494–495, 2006). Over 20 mutations have been identified in patients with AVED. In the present paper we summarize the recent findings on molecular genetic of this disease including the list of the known mutations.     

Isolated vitamin E deficiency with demyelinating neuropathy

A 22-year-old man, with a past history of generalized tonic-clonic seizures treated with phenobarbital, presented with spinocerebellar ataxia. The electrophysiological studies revealed a demyelinating motor-sensory neuropathy. The serum vitamin E level was low. Sural nerve biopsy revealed loss of large myelinated fibers with evidence of remyelination. Vitamin E supplementation led to clinical and electrophysiological recovery of sensory conduction and evoked potentials. Motor nerve conduction, however, showed only partial recovery. Vitamin E deficiency leading to a demyelinating neuropathy, as in the present case, suggests that the full spectrum of the disease entity is not fully defined.     

Neuromyopathy and vitamin E deficiency in man

A 12-year-old boy, born of a consanguineous marriage, had ataxia, sensory neuropathy, generalized muscle hypotrophy and a lower serum vitamin E level. Two of his relatives had died of a clinically similar disorder in their late adolescence. Morphologically, his striated muscle fibers and Schwann cells of his sural nerve contained numerous autofluorescent acid phosphatase-positive lipopigments which, by electron microscopy, consisted of a finely granular matrix surrounded by a trilaminar membrane. These lysosomal lipopigments were similar to those observed in muscle fibers of a patient afflicted with abeta-lipoproteinemia. They probably represent the morphological sequelae of long-standing vitamin E deficiency in this child, the extract origin of which has not been fully elucidated.     

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.     

The spectrum of neurologic disorder from vitamin E deficiency

We describe nine patients with fat malabsorption in whom a spectrum of vitamin E deficiency was present. Early deficiency was generally asymptomatic, and intermediate deficiency produced some impairment. Ataxia, weakness, reflex changes, impaired vision, and pigment retinopathy were associated with chronic, advanced deficiency. In the last group, delayed central somatosensory conduction and amplitude reduction of the electroretinogram were present. In adults, a severe vitamin E deficiency state existed for more than 5 years before producing measurable neurologic damage. The clinical picture is less homogeneous than previously suggested, and electrophysiologic abnormalities need not predate clinical dysfunction.     

Reversibility of human myopathy caused by vitamin E deficiency

Although a neuromuscular syndrome has been induced experimentally by vitamin E deficiency, a human syndrome has not yet been documented. This report describes a 7-year-old boy with severe malabsorption since birth who presented with progressive external ophthalmoplegia, proximal muscle weakness, peripheral neuropathy, hyporeflexia, and bilateral Babinski signs. Abnormalities on neurologic examination included elevated creatine phosphokinase and aldolase, slowed distal sensory latencies, type II muscle fiber atrophy, and a plasma vitamin E level of 8 microgram per deciliter (normal, 550-1500 microgram per deciliter). Treatment with oral water-solubilized vitamin E (400 IU daily; greater than 50 times the normal daily intake) was begun, with repeat laboratory studies at 3-month intervals. Over a 16-month period, plasma vitamin E content gradually increased to 350 microgram per deciliter, associated with declining sarcoplasmic enzyme activities and clinical improvement.     

Isolated deficiency of vitamin E with progressive neurologic deterioration

We studied a 19-year-old man with vitamin E deficiency without intestinal fat malabsorption. In addition to recognized neurologic complications of vitamin E deficiency, he had dystonic posturing and bradykinesia.     

Electrophysiologic features of muscle regeneration

Extracellular and intracellular recordings of directly evoked action potentials were used to detect the restoration of functional continuity in regenerating rat semitendinosus muscle fibers. After a crush lesion, muscle fibers became almost fully depolarized at the site of injury and some decrease in resting potential could be detected several millimeters on either side of the lesion. Functional continuity was reestablished in some fibers by the 5th day and in all fibers by the 30th day after crushing. At first, impulse propagation was delayed in the regenerating segments of fibers but normal response latencies were attained by the 30th day.     

A review of the health consequences of the vitamin D deficiency pandemic

Rickets, osteomalacia, osteoporosis and myopathy are among the better known consequences of a low to very low vitamin D status. Over the past several years various predominantly epidemiological and prospective cohort studies have found associations between low vitamin D levels and various extraskeletal conditions. These findings may particularly become important over the next years since large proportions of the population have low vitamin D levels. Increasing incidence rates of obesity, adverse life-style factors and active avoidance of sunlight seem to decrease average population mean vitamin D levels further. This article gives a brief overview of known and also less well-established potential detrimental effects of a low vitamin D status.     

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.     

Familial idiopathic vitamin E deficiency associated with cerebellar atrophy

Sibling cases of familial vitamin E deficiency accompanied by ataxia, polyneuropathy and mental retardation were reported. Case 1 was a 37-year-old male who developed progressive gait disturbance, deformity of the feet and head tremor from childhood, after normal delivery and development of early childhood. On physical examination, he had cataract, high arched palate and pes cavus. Neurological examination revealed mental retardation (WAIS 68), scanning speech, muscular atrophy of the face and extremities with predominance in the lower limbs, absent Achilles tendon reflex, disturbance of superficial and deep sensation predominant in distal limbs, and marked gait ataxia. Ataxia was both cerebellar and sensory in nature. Laboratory data of the blood showed no significant abnormalities including blood glucose and vitamin B12 except a markedly low level of serum vitamin E. The brain CT scan revealed severe cerebellar atrophy and marked dilatation of the cisterna magna and the subarachnoid space around the cerebellum. Motor nerve conduction velocity in the leg was decreased. Biopsy specimen from the quadriceps muscle showed neurogenic atrophy. Sural nerve biopsy revealed decrease in large myelinated fibers with axonal degeneration and regeneration. Oral administration of alpha-tocopherol acetate, 600 mg per day, diminished ataxia significantly. Based on lysosomal enzyme activity in leukocytes, clinical and laboratory examination, lipidosis or spinocerebellar degeneration was excluded. Chronic lipid malabsorption or beta lipoprotein deficiency which can cause decrease in vitamin E absorption, was not recognized. On oral loading with 2 g of alpha-tocopherol acetate, the decrease rate of serum vitamin E was normal. Consequently the low vitamin E was considered to have resulted from selective impairment of vitamin E absorption.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ataxia with isolated vitamin E deficiency and retinitis pigmentosa

We used computer pattern recognition of proton magnetic resonance spectroscopic image data to differentiate between brain tumors and large, isolated, demyelinating lesions of the type seen in multiple sclerosis. Leave-one-out linear discriminant analyses correctly classified resonance profiles from five acute demyelinating lesions, 20 low-grade astrocytomas, 22 anoplastic astrocytomas, and 24 glioblastomas. Classification of nonacute lesions will require further development, as the metabolic profiles of demyelinating lesions evolve over time.     

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.