M.T. Dotti

Increase of serum levels of vitamin E during human aging: Is it a protective factor against death?

During the recent years, numerous reports have focused the attention on the role of vitamin E as a trophic factor in normal function of the nervous system and in protection against aging or other age related pathologies as tumors, Parkinsons disease and several spino-cerebellar syndromes. We have previously reported cases with severe neurological diseases, including peripheral and central pathology due to abnormality of primary symptoms after vitamin E supplementation. Here we report the results of our studies on the changes of serum concentration of vitamin E during development and aging. vitamin E has been measured in the serum of 479 normal subjects from the birth to the age of 106 years, groupped as follows: below 20; 20-40; 40-60; 60-80; 80-100 and above 100 years. The results, show a linear increase of serum vitamin E values (18 mumole/l in the youngest group to 33.2 mumole/l in the centenarians). The data may be related to higher vitamin E intake during aging or to higher adsorption, or to minor catabolism and utilization. In any case, the highest vitamin E availability during aging has been shown and its role in protection against death is discussed.

Auditory neuropathy in a patient with mitochondrial myopathy and multiple mtDNA deletions

Auditory neuropathy (AN) is a hearing disorder characterized by the absence or severe distortion of the auditory brainstem responses, in the presence of preserved otoacoustic emissions. This peculiar combination suggests the presence of a defect impinging upon the functional complex formed by inner hair cells, the primary afferents (spiral ganglion neurones) and the first order synapses between hair cells and the cochlear nerve. Typically, AN patients show a severe speech perception impairment, which appears reduced out of proportion to pure tone threshold, but the clinical presentation of AN is quite complex. Hearing loss is a common symptom associated with mitochondrial diseases; however, AN has only rarely been reported in these disorders. Here we report a rare association, the first case observed in Italy, in a patient with autosomal recessive mitochondrial myopathy and mitochondrial DNA multiple deletions, and a hearing deficit with the audiological and electrophysiological features of AN.

Congenital lactic acidosis due to a defect of pyruvate dehydrogenase complex (E1). Clinical, biochemical, nerve biopsy study and effect of therapy.

We report an 8-year-old patient with clinical features suggesting Leighs syndrome and with a decreased activity of the E1 component of the pyruvate dehydrogenase complex in cultured skin fibroblasts. A nerve biopsy showed the presence of severe peripheral neuropathy, rarely described in the literature. The partial correction of lactic acidosis with oral sodium bicarbonate chronic therapy may result in a slow evolution of the clinical symptoms.

Adrenomyeloneurodystrophy with late cerebral involvement and evidence of a multiple autoimmune disorder

The classical form of adrenoleukodystrophy (ALD; McKusick 20237) has infantile onset. Adrenomyeloneurodystrophy (AMN), having genetic, biochemical and ultrastructural features closely correlated to those of ALD, has been described in adults (Griffin et al., 1977). AMN is clinically characterized by spastic paraparesis, adrenal insufficiency, peripheral neuropathy and variable degree of hypogonadism.

Histochemical, Ultrastructural and Biochemical Study of Muscle Mitochondria in Leber’s Hereditary Optic Atrophy

Leber’s hereditary optic atrophy (McKusick 30890) is characterized by severe abiotrophy of the pregeniculate optic pathway with acute onset in young adults, often without any other neurological symptoms. Most of the affected patients are male, but the disease is usually transmitted by the female. The mechanism of this genetic non-mendelian maternal hereditary transmission is not yet known, but the most probable hypothesis is mitochondrial inheritance, as mitochondria and their genetic heritage are of maternal origin.

Enlarging brain xanthomas in a patient with cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis (CTX) is a rare metabolic disorder caused by the inherited deficiency of the mitochondrial enzyme sterol 27-hydroxylase, which results in reduced synthesis of bile acids and systemic accumulation of cholestanol and cholesterol (Federico et al. 2003). Sterol storage in the central nervous system is the main cause of disability in this disease. Brain xanthomas and degenerative brain changes at magnetic resonance imaging (MRI) are among the hallmarks of CTX. Chenodeoxycholic acid (CDCA) taken orally is standard therapy in patients with CTX on account of its ability to normalize the altered bile synthesis (Berginer et al. 1984). Here we report a 56-year old patient with CTX whose MRIs showed a marked enlargement of two brain xanthomas despite maintenance CDCA treatment since age 31 (Fig. 1). As CDCA may not be able to stop the progression of neurological damage in all patients with CTX, brain MRI is indicated in the follow-up of patients with this disease.

Inclusion Body Myopathy-Like Changes in a Family with Cerebellar Atrophy, Mental Retardation and Abnormal Pupils

derstood, dysphagia had worsened, cognitive function had deteriorated and the patient was no longer self-sufficient. On hospitalization in our department at age 28 years, neurological examination showed severe mental retardation (IQ 48), ataxic gait, diffuse hypotonia and mild muscle hypotrophy, unintelligible speech and hypernasal voice, dysphagia, slight upward gaze palsy, strabismus, anisocoria with unreactive pupils, slight dysmetria, and hypoactive deep tendon reflexes. Routine blood chemistry, including CK, LDH, pyruvic and lactic acid, carnitine, vitamin E, and thyroid hormones, was normal. Electrocardiography showed partial right branch block. Echocardiography and chest x-ray were normal. Tilting test showed significantly reduced heart rate variability and very high vagal tonus. Brain MRI confirmed severe cerebellar atrophy ( fig. 1 A) and small areas of signal hyperintensity in the olivary nuclei. EMG showed myopathic alterations. Peripheral nerve conduction velocities were in the normal range. Two years later, the patient was readmitted to our department for recurrent episodes of severe constipation lasting 2–3 weeks. Neurological examination was substantially unchanged apart from absent deep tendon reflexes. Abdominal x-ray and intestinal transit studies showed marked slowing (96 h to reach sigma and 148 h to reach rectum). The patient was successfully treated with intravenous Dear Sir, The presence of rimmed vacuoles and intranuclear tubulofilamentous inclusions in muscle fibers is characteristic of disorders such as inclusion body myopathies (IBM) [1–3] , oculopharyngeal muscular dystrophy [4] and distal myopathies [5] . Autosomal recessive and dominant forms of the above syndromes, in which the central nervous system (CNS) is not usually involved, have been reported [1–3, 5] . Here we describe an apparently autosomal dominant syndrome of mental retardation, cerebellar atrophy and abnormal pupils, associated with muscle biopsy evidence of rimmed vacuoles and tubulofilamentous inclusions.

Infanto-Juvenile Encephaloneuropathy and Pigmentary Retinopathy in a Girl Associated with Congenital Adrenal Insufficiency and Altered Plasma Medium-Chain Fatty Acid Levels

The combination of adrenocortical insufficiency, pigmentary retinopathy, seizures, peripheral neuropathy and hepatomegaly was first reported by Dyck et al. (1981) in two male subjects and was associated with decreased hepatic arachidonic acid. In 1978, Allgrove et al. reported four cases, one of them female, from two different families, with adrenocortical deficiency, achalasia, decreased lachrymation and autonomic dysfunction.

Morphometric and Biochemical Study of Muscle Mitochondria in Adult Chronic Progressive External Ophthalmoplegia

Adult chronic progressive external ophthalmoplegia (ACPEO) is characterized by slowly progressive paralysis of the extraocular muscles, with or without other neurological manifestations. The presence of ragged red fibres (Olsen et al., 1972) and the fact that abnormalities in the mitochondrial compartment are often the most striking ultrastructural findings in the syndrome raises the possibility of a failure of oxidative energy metabolism in the pathogenesis of the disease. This supposition is supported by the finding of excessive lactic acidosis after exercise in several cases, suggesting a defective utilization of pyruvate (Scarlato et al., 1980).