Children with Leigh Syndrome Seen to Retain Better Functional Abilities Than Reported

Magdalena Kegel avatar

by Magdalena Kegel |

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Leigh Syndrome

Early onset and extensive brain lesions are predictors of a poor prognosis in patients with Leigh syndrome, a mitochondrial disease affecting infants and small children. But findings also suggest that clinical outcomes of the syndrome, in terms of function, might be better than previously believed.

Leigh syndrome is a neurodegenerative disorder caused by a dysfunctional mitochondrial respiratory complex. Composed of an array of proteins of both mitochondrial and nuclear origin, the complex and its function can be affected by mutations in either genome. The condition may present as psychomotor retardation, seizures, hypotonia, dystonia, gait disturbance, and respiratory dysfunction of varying severity. Patients also have neurodegenerative lesions, identified by radiological brain imaging, in one or more brain regions, including the basal ganglia, thalamus, brainstem, and cerebellum.

Once symptoms appear, they worsen progressively, although cases with late onset and slow progression have also been described. But up to now, few studies have explored if clinical and neurological features or radiological findings could be used to predict prognosis of this severe childhood disorder.

Researchers at Gachon University Gil Medical Center, Korea, scrutinized medical records and neuroimaging findings, as well as histological and biochemical observations, in skeletal muscle biopsies from 39 Leigh syndrome patients. The research team also sequenced the mitochondrial genome, searching for mitochondrial respiratory chain (MRC) enzyme mutations.

Patient ages ranged from 2 months to 21 years at study start, and 13 percent had a family history of Leigh syndrome. A majority became ill before the age of 2. Most patients, 74 percent, also experienced a progressive neurological worsening, while 10 remained stable during study follow-up.

The mean functional outcome score was 5.7 points on a scale ranging from 3 to 8 points, indicating that outcomes were relatively good. A total of 63 percent of the patients had an intact walking ability, with 24 percent capable of walking without aid and another 39 percent walking with assistance. Most patients were fed orally, and seven could eat independently. Also, only 12 percent were dependent on a mechanical ventilator to breathe.

Dysfunctional mitochondrial respiratory chain complex was observed in 84 percent of patients. The energy-producing respiratory chain complex is composed of several complexes working in a coordinated manner. The study, Leigh Syndrome in Childhood: Neurologic Progression and Functional Outcome, found that isolated complex I deficiency was the most common type of defect, followed by various combinations of dysfunctional mitochondrial complexes.

Neither the presence of mutations in the mitochondrial DNA nor isolated complex I deficiency could predict the clinical course and functional outcomes of the participants. The findings, published in the Journal of Clinical Neurology, also indicated that there was no correlation between neuroradiological findings and the presence of mitochondrial DNA mutations.

In contrast, poor functional outcomes and neurological deterioration were associated with a disease onset during the first year of life, and the presence of seizures when the disease first manifested. Imaging findings of lesions other than those affecting the basal ganglia were also linked to worse outcomes.

The team concluded that the outcome of Leigh syndrome and neurological severity may vary widely, although it seems to be better than predicted in previous studies. Researchers suggest that age at onset and initial neuroimaging findings could be used as prognostic factors in patients with Leigh syndrome.