Adult Leigh Disease Without Failure to Thrive

Sakushima, Ken; Tsuji-Akimoto, Sachiko; Niino, Masaaki; Saitoh, Shinji; Yabe, Ichiro; Sasaki, Hidenao

doi:10.1097/nrl.0b013e318217357a

Cited by 14 publications

(11 citation statements)

References 10 publications

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“…RRF, a hallmark of some mitochondrial diseases, is rare in LS (19) and is also not seen in our patient. In muscle biopsies of LS patients, a variety of changes in histologic and ultrastructural examination may be seen, such as lipid accumulation, COX-negative fibers, succinate dehydrogenase deficiency or abnormal mitochondrial configurations, or the muscle biopsy may be completely normal (13, 14, 19, 46).…”

Section: Discussionmentioning

confidence: 99%

A Chinese Family With Adult-Onset Leigh-Like Syndrome Caused by the Heteroplasmic m.10191T>C Mutation in the Mitochondrial MTND3 Gene

Wang

Liu

et al. 2019

Front. Neurol.

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Leigh syndrome (LS) is a mitochondrial disease of infancy and early childhood, that is rarely seen in adults. The high degree of genetic and clinical heterogeneity makes LS a very complex syndrome. The clinical manifestations include neurological symptoms and various non-neurological symptoms, with different mutations differing in presentations and therapies. The m.10191T>C mutation in the mitochondrial DNA gene encoding in the respiratory chain complex I (CI) subunit of MTND3 results in the substitution of a highly conserved amino acid (p.Ser45Pro) within the ND3 protein, leading to CI dysfunction and causing a broad clinical spectrum of disorders that includes LS. Patients with the m.10191T>C mutation are rare in general, even more so in adults. In the present study, we report a family of patients with very rare adult-onset Leigh-like syndrome with the m.10191T>C mutation. The 24-year-old proband presented with seizures 6 years ago and developed refractory status epilepticus on admission. She had acute encephalopathy accompanied by lactic acidosis, symmetrical putamen and scattered cortical lesions. The video electroencephalogram suggested focal-onset seizures. She harbored the heteroplasmic m.10191T>C mutation in her blood and fibroblasts. Her aunt was diagnosed with mitochondrial disease at the age of 42, and had the heteroplasmic m.10191T>C mutation in her fibroblasts. Her aunt's son (cousin) died of respiratory failure at the age of 8, and we suspected he was also a case of LS. Furthermore, we reviewed the previously reported patients with the m.10191T>C mutation and summarized their characteristics. Recognizing the characteristics of these patients will help us improve the clinical understanding of LS or Leigh-like syndrome.

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Section: Discussionmentioning

confidence: 99%

A Chinese Family With Adult-Onset Leigh-Like Syndrome Caused by the Heteroplasmic m.10191T>C Mutation in the Mitochondrial MTND3 Gene

Wang

Liu

et al. 2019

Front. Neurol.

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“…More than 50% of cases are observed in patients within one year of age, usually six months old. Late-onset LS is rare worldwide (18). Karin et al described 25 patients with LS, and all 25 patients had age onset younger than 2 years (16).…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics of Early-Onset and Late-Onset Leigh Syndrome

Hong

Park

et al. 2020

Front. Neurol.

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Background: Leigh syndrome (LS) is the most common pediatric mitochondrial diseases caused by MRC defect. LS patients typically have onset age before 2 years old and have various clinical features. The purpose of this study was to evaluate the various characteristics between the group that were early onset and late onset patients. Methods: The medical records of this study used records between 2006 and 2017 (N = 110). Clinical characteristics, diagnostic evaluations, and neuro image studying of LS were reviewed in our study. We statistically analyzed data from patients diagnosed with LS at our hospital by using subgroup analysis was performed to divide patients according to the onset age. Results: Among the patients, 89 patients (80.9%) had the onset age before 2 years old, and 21 patents (19.1%) had onset age after 2 years old. In subgroup analysis first clinical presentation age, diagnosis age and several onset symptoms in the clinical characteristics were statistically significant. Early onset age group showed delayed development and late onset age group showed motor weakness and ataxia. However, Diagnostics evaluation and MRI findings showed no significant differences. The clinical status monitored during the last visit showed statistically significant differences in the clinical severity. In the early onset age group clinical status was more severe than late onset age group. Conclusions: Although the onset of Leigh syndrome is known to be under 2 years, there are many late onset cases were existed more than expected. Early onset LS patients have poor prognosis compare with late onset LS patients. Therefore, the specific phenotype according to the age of onset should be well-observed. Onset of LS is important in predicting clinical severity or prognosis, and it is necessary to provide individualized treatment or follow-up protocols for each patient.

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“…Leigh syndrome is a progressive disease, although patients may be misdiagnosed with "cerebral palsy" or "hypoxic-ischemic encephalopathy" [94]. Leigh syndrome has been reported in some adults, although it is a diagnosis made much more typically in children and usually carries a poor prognosis [47,95,96]. Leigh syndrome has many causes, mainly nuclear-encoded genes, including pyruvate dehydrogenase complex (PDHC) deficiency, deficiencies in complex I subunits and assembly factors, COX subunits, and assembly factors SURF1 and PDSS2 causing primary CoQ10 deficiency [97][98][99][100][101].…”

Section: Stroke-like Lesions In Nonvascular Distributionmentioning

confidence: 99%

Mitochondrial Disease in Childhood: Nuclear Encoded

2013

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Primary mitochondrial disorders are clinically and genetically heterogeneous, caused by an alteration(s) in either mitochondrial DNA or nuclear DNA, and affect the respiratory chain's ability to undergo oxidative phosphorylation, leading to decreased production of adenosine triphosphophate and subsequent energy failure. These disorders may present at any age, but children tend to have an acute onset of disease compared with subacute or slowly progressive presentation in adults. Varying organ involvement also contributes to the phenotypic spectrum seen in these disorders. The childhood presentation of primary mitochondrial disease is mainly due to nuclear DNA mutations, with mitochondrial DNA mutations being less frequent in childhood and more prominent in adulthood disease. The clinician should be aware of the pediatric presentation of mitochondrial disease and have an understanding of the myriad of nuclear genes responsible for these disorders. The nuclear genes can be best understood by utilizing a classification system of location and function within the mitochondria.

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Adult Leigh Disease Without Failure to Thrive

Abstract: Introduction:

Cited by 14 publications

References 10 publications

A Chinese Family With Adult-Onset Leigh-Like Syndrome Caused by the Heteroplasmic m.10191T>C Mutation in the Mitochondrial MTND3 Gene

A Chinese Family With Adult-Onset Leigh-Like Syndrome Caused by the Heteroplasmic m.10191T>C Mutation in the Mitochondrial MTND3 Gene

Clinical Characteristics of Early-Onset and Late-Onset Leigh Syndrome

Mitochondrial Disease in Childhood: Nuclear Encoded

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