Treatment of chronic congenital lactic acidosis by oral administration of dichloroacetate

Kuroda, Yasuhiro; M, Ito; Toshima, Kenji; Takeda, Eiji; Naito, Etsuo; Hwang, Tai Ju; Hashimoto, Tadashi; Miyao, Masaru; Masuda, Midori; Yamashita, Kyoko; Adachi, Tatsumi; Suzuki, Yoshitaka; Nishiyama, Keitaro

doi:10.1007/bf01799655

Cited by 33 publications

(8 citation statements)

References 22 publications

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“…These data suggest that the concomitant administration of a full dosage of thiamine and DCA may be required to achieve maximal activity of PDHC in patients with lactic acidaemia. Therefore, a full dosage of DCA (50 mg/kg every 12 h) and thiamine (100± 200 mg/day) should be given initially to achieve maximal activity of PDHC in patients with thiamine-responsive PDHC de®ciency or lactic acidaemia of unknown origin, especially in those with an acidotic crisis [8]. …”

Section: Discussionmentioning

confidence: 99%

Thiamine-responsive lactic acidaemia: role of pyruvate dehydrogenase complex

Naito

Yokota

et al. 1998

European Journal of Pediatrics

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Section: Discussionmentioning

confidence: 99%

Thiamine-responsive lactic acidaemia: role of pyruvate dehydrogenase complex

Naito

Yokota

et al. 1998

European Journal of Pediatrics

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“…Roodhoft et al [18] administered a combination of camitine, riboflavin, nicotinamide, L-va-line, L-isoleucine, and ubiquinone to a 4-month-old infant with a combined complex I and complex IV defect. Thiamine is the coenzyme for pyruvate dehydrogenase [9,10,21]. The lactate concentration was elevated before therapy in blood and CSF, no comments are available on these values after cessation of therapy.…”

Section: Discussionmentioning

confidence: 99%

Therapy of complex I deficiency: Peripheral neuropathy during dichloroacetate therapy

et al. 1995

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A therapeutic trial with polyvitamins and dichloroacetate (DCA) in combination with thiamine in a 13-year-old girl with complex I deficiency is reported. The polyvitamin therapy included thiamine, riboflavin, ascorbate, coenzyme Q 10 and carnitine. This therapeutic regine was used over a period of 17 months without any effect. Although DCA lowered the lactate concentration in blood and CNS--measured by magnetic resonance spectroscopy--no clinical benefit was achieved. After 20 weeks of DCA therapy a distal polyneuropathy with areflexia developed although 100 mg thiamine daily as comedication was given from the beginning of DCA therapy. Nerve conduction velocity of the peroneal nerve was not detectable, sensible evoked potentials of the tibialis posterious nerve were normal. This side-effect resolved completely within 6 months after omission of DCA. Our observation suggests a direct toxic effect of DCA only on the peripheral nervous system in our patient since several cerebral MRI and magnetic resonance spectroscopy studies showed no abnormalities. CONCLUSION. DCA lowers the lactate concentration in children with complex I deficiency of the respiratory chain in a dose of 100 mg/kg body weight without clinical benefit. Reversible peripheral polyneuropathy may develop under DCA therapy despite thiamine medication.

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“…A previous report about treatment of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke‐like episodes (MELAS) showed that DCA concentrations in serum should be between 100 and 120 µg/mL 2 h after DCA administration 3 . It has also been reported that the DCA dose must be determined by monitoring the concentration of lactic acid and DCA because DCA tends to accumulate in tissue 4 …”

Section: Discussionmentioning

confidence: 99%

Treatment for Leigh syndrome by monitoring dichloroacetate concentration

Katsumi

Morimoto

Nishimura

et al. 2009

Pediatrics International

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Key words lactic acid, Leigh syndrome, sodium dichloroacetate.Leigh syndrome (LS), otherwise know as subacute necrotizing encephalopathy, is characteristic of multiple symmetric lesions in the basal ganglia, thalamus, cerebellum, and brainstem in infancy and childhood. There are a variety of clinical manifestations of LS, such as seizures, ataxia, psychomotor retardation, dystonia, or muscle weakness. 1 This syndrome has a poor prognosis despite treatment with several types of medicine. Here, we describe a case of LS in a patient who temporarily needed a higher volume of sodium dichloroacetate (DCA) than normal, which could be tapered without LS progression by the monitoring of DCA concentration and lactic acid in serum and cerebrospinal fluid (CSF). Case reportA boy had been born uneventfully to non-consanguineous, healthy parents, and weighed 3180 g at 41 weeks gestation. He had grown normally before 10 months of age. Three months before admission he presented a blank face and had constipation. Muscle weakness was found at the 10 month checkup. Then, because he had bradykinesia and lethargy, he was admitted, at 13 months of age, to another hospital, where computed tomography (CT) of the brain indicated low-density lesions in the basal ganglia, cerebellum and brainstem. The levels of lactic and pyruvic acid were 0.89 mmol/L and 73.8 mmol/L in serum, and 2.45 mmol/L and 117 mmol/L in CSF, respectively. The patient was then transferred to University Hospital, Kyoto Prefectural University of Medicine for treatment for mitochondrial encephalopathy.On admission he remained conscious, but he could not sit, crawl, or stand without support owing to hypotonia in his trunk and extremities. Hematologic laboratory values were normal. The levels of lactic and pyruvic acid were 0.91 mmol/L and 68.1 mmol/L in serum, and 3.0 mmol/L and 113 mmol/L in CSF, respectively (Fig. 1). Magnetic resonance imaging (MRI) of the brain showed low-intensity areas on T1-weighted imaging and high-intensity areas on T2-weighted imaging or fluid-attenuated inversion recovery (FLAIR) imaging in the bilateral basal ganglia, cerebellum, and brainstem ( Fig. 2a-d). Magnetic resonance spectroscopy (MRS) showed an increase in lactic acid and a decrease in N-acetylaspartate (NAA) levels in the basal ganglia, which had an abnormal MRI appearance. There were no mutations of mitochondrial DNA in genomic positions, which have been reported for mutations associated with LS, There was no abnormality of activity in pyruvate dehydrogenase complex (PDHC) or defective respiratory-chain complexes, in peripheral blood lymphocytes. We did not perform a muscle biopsy, due to the wishes of the patient's parents. Therefore, we clinically diagnosed the patient as having LS because of the onset age, the regressive neurological symptoms, the increase in lactic and

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Treatment of chronic congenital lactic acidosis by oral administration of dichloroacetate

Cited by 33 publications

References 22 publications

Thiamine-responsive lactic acidaemia: role of pyruvate dehydrogenase complex

Thiamine-responsive lactic acidaemia: role of pyruvate dehydrogenase complex

Therapy of complex I deficiency: Peripheral neuropathy during dichloroacetate therapy

Treatment for Leigh syndrome by monitoring dichloroacetate concentration

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