Intracellular phosphates in inclusion body myositis—A 31P magnetic resonance spectroscopy study

Argov, Zohar; Taivassalo, Tanja; Stefano, Nicola De; Genge, Angela; Karpati, George; Arnold, Douglas L.

doi:10.1002/(sici)1097-4598(199811)21:11<1523::aid-mus22>3.3.co;2-a

Cited by 2 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, a rise in intracellular [P i ] also is found in other neuromuscular disorders where a defect of mitochondrial respiration cannot be demonstrated (19,(21)(22)(23), which is true for the disease control group reported in Table 1. Therefore, the available evidence suggests that the increased P i concentration is a nonspecific indicator of abnormal skeletal muscle metabolism.…”

Section: Resultsmentioning

confidence: 99%

Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia

Lodi

Cooper²,

Bradley³

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

328

194

View full text Add to dashboard Cite

Friedreich ataxia (FRDA), the most common of the inherited ataxias, is an autosomal recessive degenerative disorder, characterized clinically by onset before the age of 25 of progressive gait and limb ataxia, absence of deep tendon ref lexes, extensor plantar responses, and loss of position and vibration sense in the lower limbs. FRDA is caused by a GAA triplet expansion in the first intron of the FRDA gene on chromosome 9q13 in 97% of patients. The FRDA gene encodes a widely expressed 210-aa protein, frataxin, which is located in mitochondria and is severely reduced in FRDA patients. Frataxin function is still unknown but the knockout of the yeast frataxin homologue gene (YFH1) showed a severe defect of mitochondrial respiration and loss of mtDNA associated with elevated intramitochondrial iron. Here we report in vivo evidence of impaired mitochondrial respiration in skeletal muscle of FRDA patients. Using phosphorus magnetic resonance spectroscopy we demonstrated a maximum rate of muscle mitochondrial ATP production (V max ) below the normal range in all 12 FRDA patients and a strong negative correlation between mitochondrial V max and the number of GAA repeats in the smaller allele. Our results show that FRDA is a nuclear-encoded mitochondrial disorder affecting oxidative phosphorylation and give a rationale for treatments aimed to improve mitochondrial function in this condition.Friedreich ataxia (FRDA) is the most common form of inherited ataxia with a frequency of 1 in 50,000 live births. FRDA is an autosomal recessive degenerative disorder, characterized clinically by onset before the age of 25 of progressive gait and limb ataxia, absence of deep tendon reflexes, extensor plantar responses, and loss of position and vibration sense in the lower limbs (1). Cardiomyopathy as defined by echocardiography is present in more than 60% of FRDA patients (2). The cause of FRDA is a GAA triplet expansion in the first intron of the FRDA gene on chromosome 9q13 (3). Ninetyseven percent of FRDA patients are homozygous for the GAA expansion, the remainder carrying a repeat expansion in one FRDA allele and a point mutation in the other (2, 3).The FRDA gene encodes a widely expressed 210-aa protein, frataxin, which is located in mitochondria (4-6) and is severely reduced in FRDA patients (4). Although frataxin function is still unknown, yeast strains carrying a disruption in the frataxin homologue gene (YFH1) showed a severe defect of mitochondrial respiration (5-8) and loss of mtDNA (7, 8) associated with elevated intramitochondrial iron (5,8).In view of the mitochondrial localization of frataxin (4-6), the evidence from the YFH1 knockout model for mitochondrial dysfunction (5-8), and the similarities of the cardinal clinical features present in FRDA with primary mitochondrial diseases (9), we used in vivo 31 phosphorus magnetic resonance spectroscopy ( 31 P-MRS) to test for the presence of mitochondrial dysfunction in skeletal muscle of 12 FRDA patients. Skeletal muscle is an ideal tissue in which to assess in vi...

show abstract

Section: Resultsmentioning

confidence: 99%

Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia

Lodi

Cooper²,

Bradley³

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

328

194

View full text Add to dashboard Cite

show abstract

Mitochondriopathies

Finsterer

2004

Euro J of Neurology

205

158

View full text Add to dashboard Cite

Mitochondriopathies (MCPs) are either due to sporadic or inherited mutations in nuclear or mitochondrial DNA located genes (primary MCPs), or due to exogenous factors (secondary MCPs). MCPs usually show a chronic, slowly progressive course and present with multiorgan involvement with varying onset between birth and late adulthood. Although several proteins with signalling, assembling, transport, enzymatic function can be impaired in MCP, most frequently the activity of the respiratory chain (RC) protein complexes is primarily or secondarily affected, leading to impaired oxygen utilization and reduced energy production. MCPs represent a diagnostic challenge because of their wide variation in presentation and course. Systems frequently affected in MCP are the peripheral nervous system (myopathy, polyneuropathy, lactacidosis), brain (leucencephalopathy, calcifications, stroke-like episodes, atrophy with dementia, epilepsy, upper motor neuron signs, ataxia, extrapyramidal manifestations, fatigue), endocrinium (short stature, hyperhidrosis, diabetes, hyperlipidaemia, hypogonadism, amenorrhoea, delayed puberty), heart (impulse generation or conduction defects, cardiomyopathy, left ventricular non-compaction heart failure), eyes (cataract, glaucoma, pigmentary retinopathy, optic atrophy), ears (deafness, tinnitus, peripheral vertigo), guts (dysphagia, vomiting, diarrhoea, hepatopathy, pseudo-obstruction, pancreatitis, pancreas insufficiency), kidney (renal failure, cysts) and bone marrow (sideroblastic anaemia). Apart from well-recognized syndromes, MCP should be considered in any patient with unexplained progressive multisystem disorder. Although there is actually no specific therapy and cure for MCP, many secondary problems require specific treatment. The rapidly increasing understanding of the pathophysiological background of MCPs may further facilitate the diagnostic approach and open perspectives to future, possibly causative therapies.

show abstract

Intracellular phosphates in inclusion body myositis—A 31P magnetic resonance spectroscopy study

Cited by 2 publications

References 0 publications

Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia

Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia

Mitochondriopathies

Contact Info

Product

Resources

About