Arginine therapy in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes

Ikawa, Masamichi; Povalko, Nataliya; Koga, Yasutoshi

doi:10.1097/mco.0000000000000610

Cited by 26 publications

(15 citation statements)

References 25 publications

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“…The primary endpoint was the improvement in rates of headache and nausea/vomiting at 2 h after completion of the initial intravenous administration. Although there was improvement in symptoms, this outcome measure did not reach the study target of 30% improvement in 2 h. The authors speculated that extending the window for intravenous arginine administration from 3 h in their previous study to 6 h in this study may partly explain these findings (Koga et al, 2018;Ikawa et al, 2020; Table 1).…”

Section: Arginine and Citrulline In Mitochondrial Disordersmentioning

confidence: 62%

Nitric Oxide Deficiency in Mitochondrial Disorders: The Utility of Arginine and Citrulline

Almannai

El‐Hattab

2021

Front. Mol. Neurosci.

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Mitochondrial diseases represent a growing list of clinically heterogeneous disorders that are associated with dysfunctional mitochondria and multisystemic manifestations. In spite of a better understanding of the underlying pathophysiological basis of mitochondrial disorders, treatment options remain limited. Over the past two decades, there is growing evidence that patients with mitochondrial disorders have nitric oxide (NO) deficiency due to the limited availability of NO substrates, arginine and citrulline; decreased activity of nitric oxide synthase (NOS); and NO sequestration. Studies evaluating the use of arginine in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) presenting with stroke-like episodes showed symptomatic improvement after acute administration as well as a reduction in the frequency and severity of stroke-like episodes following chronic use. Citrulline, another NO precursor, was shown through stable isotope studies to result in a greater increase in NO synthesis. Recent studies showed a positive response of arginine and citrulline in other mitochondrial disorders besides MELAS. Randomized-controlled studies with a larger number of patients are warranted to better understand the role of NO deficiency in mitochondrial disorders and the efficacy of NO precursors as treatment modalities in these disorders.

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Section: Arginine and Citrulline In Mitochondrial Disordersmentioning

confidence: 62%

Nitric Oxide Deficiency in Mitochondrial Disorders: The Utility of Arginine and Citrulline

Almannai

El‐Hattab

2021

Front. Mol. Neurosci.

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“…In the setting of the amino acid derangements that accompany OTC deficiency, plasma arginine levels must be evaluated since low levels have been associated with visual disturbances in mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) [ 6 ]. This was promptly ruled out with normal arginine levels in this patient, but still, merits consideration since OTC deficiency is commonly associated with low arginine levels due to disruption of the urea cycle [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Transient Cortical Blindness in a Toddler With Heterozygous Ornithine Transcarbamylase Deficiency

Eskander¹,

Romani²

2021

Cureus

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Ornithine transcarbamylase (OTC) deficiency is an incredibly rare disease in the subgroup of urea cycle disorders. Although typically seen in the neonate shortly after initiating high protein feeds (human breastmilk or infant formula), patients with partial/heterozygous deficiencies can often be diagnosed later in life with unique sequelae. One such manifestation is sudden, transient vision loss shortly after an initial episode of hyperammonemia in a patient without a known diagnosis of OTC deficiency. Only two such occurrences are documented in academic literature and both share many similar presenting features hinting that a hidden, but the consistent pathophysiologic mechanism of this disease is at play. Scarce research is available to propose a concise explanation; however, recent advancements in the literature point toward the brain's inability to uptake glucose and convert it into glutamate in patients with partial OTC deficiency as a likely explanation.

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“…L-arginine is involved in urea detoxification, creatine synthesis, and nitric oxide synthesis, as well as in growth and development generally. L-arginine has been proven to show clinical benefits in the treatment and prevention of the stroke-like episodes of MELAS, with long-term data suggesting improved survival and reduced debility of patients with MELAS syndrome [181,182]. Moreover, arginine and citrulline supplementation caused decreased levels of alanine and lactate in plasma, implying that such supplementation may potentially lessen lactic acidemia in MELAS syndrome through enhancing NO production, restoring perfusion, and oxygen delivery [61,183].…”

Section: Creatinementioning

confidence: 99%

Clinical Characteristics of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes

Fan

Lee

Yue

et al. 2021

Life

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Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes(MELAS)syndrome, a maternally inherited mitochondrial disorder, is characterized by its genetic, biochemical and clinical complexity. The most common mutation associated with MELAS syndrome is the mtDNA A3243G mutation in the MT-TL1 gene encoding the mitochondrial tRNA-leu(UUR), which results in impaired mitochondrial translation and protein synthesis involving the mitochondrial electron transport chain complex subunits, leading to impaired mitochondrial energy production. Angiopathy, either alone or in combination with nitric oxide (NO) deficiency, further contributes to multi-organ involvement in MELAS syndrome. Management for MELAS syndrome is amostly symptomatic multidisciplinary approach. In this article, we review the clinical presentations, pathogenic mechanisms and options for management of MELAS syndrome.

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Arginine therapy in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes

Cited by 26 publications

References 25 publications

Nitric Oxide Deficiency in Mitochondrial Disorders: The Utility of Arginine and Citrulline

Nitric Oxide Deficiency in Mitochondrial Disorders: The Utility of Arginine and Citrulline

Transient Cortical Blindness in a Toddler With Heterozygous Ornithine Transcarbamylase Deficiency

Clinical Characteristics of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes

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