We describe four patients from three independent families with the m.1644G>A in the MT-TV gene, previously reported without demonstration of its deleterious impact. Very high mutation proportion co-segregated with cytochrome oxidase defect in single muscle fibers and respiratory defect in cybrids as shown by spectrophotometric assays and polarography. The mutation appeared to have a very steep ...

We present a sibling pair with Leigh-like disease, progressive hypotonia, regression, and chronic encephalopathy. Whole exome sequencing in the younger sibling demonstrated a homozygous thiamine pyrophosphokinase (TPK) mutation. Initiation of high dose thiamine, niacin, biotin, α-lipoic acid and ketogenic diet in this child demonstrated improvement in neurologic function and re-attainment of pr...

Abstract Leigh syndrome (LS) is a severe manifestation of mitochondrial disease in children and currently incurable. The lack effective models hampers our understanding the mechanisms underlying neuronal pathology LS. Using patient-derived induced pluripotent stem cells CRISPR/Cas9 engineering, we developed human model LS caused by mutations complex IV assembly gene SURF1 . Single-cell RNA-sequ...

Abstract Leigh syndrome (LS) or subacute necrotizing encephalomyelopathy is a progressive, lethal, mitochondrial disease mostly presenting in childhood. We report 36-year-old African male to the Emergency Department with 6-month history of progressive dysarthria. Examination also showed oculomotor limitations for downgaze and convergence, mild right hemiparesis Babinski sign, absent lower limb ...

Subacute necrotizing encephalopathy was described originally by Leigh (1951). Further case reports reviewed by Ebels, Blokzijl, and Troelstra (1965) have confirmed this condition as a neuropathological entity but ideas concerning its aetiology have remained speculative. Recently Worsley, Brookfield, Elwood, Noble, and Taylor (1965) have reported a case, with confirmation at necropsy, in which t...

MEDICAL SCIENCES Correction for “Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome,” by Michele Ferrari, Isha H. Jain, Olga Goldberger, Emanuele Rezoagli, Robrecht Thoonen, Kai-Hung Chen, David E. Sosnovik, Marielle Scherrer-Crosbie, Vamsi K. Mootha, and Warren M. Zapol, which appeared in issue 21, May 23, 2017, of Proc Natl Acad Sci USA (114:E4241–E4250; f...

Scleromalacia perforans is most frequently associated with rheumatoid arthritis. A necrotizing nodular scleritis proceeding to scleromalacia perforans is sometimes seen in the collagen disorders systemic lupus erythematosus, periarteritis nodosa, and Wegener's granulomatosis. Rarely scleromalacia has been described in porphyria and herpes zoster (Duke-Elder and Leigh I 965; Fran§ois, I 95 1) . ...

Scleromalacia perforans is most frequently associated with rheumatoid arthritis. A necrotizing nodular scleritis proceeding to scleromalacia perforans is sometimes seen in the collagen disorders systemic lupus erythematosus, periarteritis nodosa, and Wegener's granulomatosis. Rarely scleromalacia has been described in porphyria and herpes zoster (Duke-Elder and Leigh I 965; Fran§ois, I 95 1) . ...

MEDICAL SCIENCES Correction for “Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome,” by Michele Ferrari, Isha H. Jain, Olga Goldberger, Emanuele Rezoagli, Robrecht Thoonen, Kai-Hung Chen, David E. Sosnovik, Marielle Scherrer-Crosbie, Vamsi K. Mootha, and Warren M. Zapol, which appeared in issue 21, May 23, 2017, of Proc Natl Acad Sci USA (114:E4241–E4250; f...