Long‐term outcome of Leigh syndrome caused by the NARP‐T8993C mtDNA mutation

Abstract

Mutations at mitochondrial DNA (mtDNA) nucleotide 8993 can cause neurogenic weakness, ataxia and retinitis pigmentosa (NARP syndrome), or maternally inherited Leigh syndrome (LS), with a correlation between the amount of mutant mtDNA and the severity of the neurological disease. The T8993C mutation is generally considered to be clinically milder than the T8993G mutation but when the level of heteroplasmy exceeds 90%, progressive neurodegeneration has been found. We report on a long-term follow-up of a patient who presented at 4 years of age with typical LS but showed an unexpected resolution of his symptoms and a favorable outcome. At 18 years of age, his neurological examination was near normal, with neither peripheral neuropathy nor retinopathy. mtDNA analysis identified the presence of T8993C mutation at high level (>95%) in the patient's blood leukocytes. This case report and literature review emphasizes the variability of the phenotypic expression of the T8993C mutation and the need for caution in predictive counseling in such patients. (c) 2007 Wiley-Liss, Inc.

Complex I deficiency due to loss of Ndufs4 in the brain results in progressive encephalopathy resembling Leigh syndrome

“…LS is regarded as the most common infantile mitochondrial disorder, and most patients exhibit symptoms before 1 mo of age (4,5). Several cases of adult-onset LS have also been reported recently (6)(7)(8)(9)(10). In vivo imaging techniques such as MRI reveal bilateral hyperintense lesions in the basal ganglia, thalamus, substantia nigra, brainstem, cerebellar white matter and cortex, cerebral white matter, or spinal cord of LS patients (6,(11)(12)(13)(14).…”

The Mitochondrial Disease Narp Syndrome in the Practice of a Pediatric Neurologist

“…Мутация T8993C считается клинически более легкой, чем T8993G, но при уровне гетероплазмии > 90 % чаще развивает-ся синдром Ли с прогрессирующей нейродегенерацией [2,9]. Наиболее часто при NARP-синдроме встречается мутация 8993Т>G, которая приводит к замене лецити-на на аргинин в цепочке ДНК [8].…”

Oftalmolojide Genetik III – Arka Segment Hastalıklar

“…COX eksikliği gözlenen Leigh sendromlu hastaların %75'inden ise nükleer genomdan kodlanan SURF1 genindeki mutasyonlar sorumludur ve bu ailelerde otozomal resesif kalıtım şekli izlenir. 18 T8993G ve T8993C mutasyonları NARP sendromuna da yol açabilir. 18 C) Retina Displazileri Retina displazileri retinanın bilateral konjenital yapısal anormallikleridir.…”

“…18 T8993G ve T8993C mutasyonları NARP sendromuna da yol açabilir. 18 C) Retina Displazileri Retina displazileri retinanın bilateral konjenital yapısal anormallikleridir. Sıklıkla santral sinir sisteminin malformasyonlarıyla birliktelik gösterir; retina ve vitreusun gelişimsel anomalisi nedeniyle doğumda retina dekolmanı olabilir.…”