Acromutilating, Paralyzing Neuropathy With Corneal Ulceration in Navajo Children

Appenzeller, Otto; Kornfeld, Mario; Snyder, R. G.

doi:10.1001/archneur.1976.00500110001001

Cited by 39 publications

(19 citation statements)

References 8 publications

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“…PNP in hepato-cerebral depletion syndrome is mostly mild and sensory [108] but occasionally sensori-motor [109] and mutilating [110]. Severe PNP has been described in the Navajo neuro-hepatopathy [107].…”

Section: Mendelian Peomentioning

confidence: 99%

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Inherited mitochondrial neuropathies

Finsterer

2011

Journal of the Neurological Sciences

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Section: Mendelian Peomentioning

confidence: 99%

“…Nerve conduction studies may be normal or may show conduction slowing but preserved CMAP and SNAP amplitude [111]. Sural nerve biopsy may show loss of myelinated fibers and nonmyelinated fibers or may show degeneration and regeneration [110].…”

Section: Mendelian Peomentioning

confidence: 99%

Inherited mitochondrial neuropathies

Finsterer

2011

Journal of the Neurological Sciences

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“…NNH was recently attributed to a specific mutation in the MPV17 protein, the p.R50Q, which originated from a single ancestral carrier common to all NNH patients (17). Clinical features of NNH/MPV17 syndrome include sensory motor neuropathy with ataxia, leukoencephalopathy, corneal ulcerations, acral mutilation, poor weight gain, short stature, sexual infantilism, serious systemic infections, and of course liver derangement (18). The same p.R50Q mutation responsible for NNH was previously found in a large MPV17 -associated MDS family from Southern Italy (13), but the mutational event was proven to have occurred independently in the two family sets (19).…”

Section: Introductionmentioning

confidence: 99%

Early-onset liver mtDNA depletion and late-onset proteinuric nephropathy in Mpv17 knockout mice

Viscomi¹,

Spinazzola²,

Maggioni

et al. 2008

Human Molecular Genetics

104

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In humans, MPV17 mutations are responsible for severe mitochondrial depletion syndrome, mainly affecting the liver and the nervous system. To gain insight into physiopathology of MPV17-related disease, we investigated an available Mpv17 knockout animal model. We found severe mtDNA depletion in liver and, albeit to a lesser extent, in skeletal muscle, whereas hardly any depletion was detected in brain and kidney, up to 1 year after birth. Mouse embryonic fibroblasts did show mtDNA depletion, but only after several culturing passages, or in a serumless culturing medium. In spite of severe mtDNA depletion, only moderate decrease in respiratory chain enzymatic activities, and mild cytoarchitectural alterations, were observed in the Mpv17−/− livers, but neither cirrhosis nor failure ever occurred in this organ at any age. The mtDNA transcription rate was markedly increased in liver, which could contribute to compensate the severe mtDNA depletion. This phenomenon was associated with specific downregulation of Mterf1, a negative modulator of mtDNA transcription. The most relevant clinical features involved skin, inner ear and kidney. The coat of the Mpv17−/− mice turned gray early in adulthood, and 18-month or older mice developed focal segmental glomerulosclerosis (FSGS) with massive proteinuria. Concomitant degeneration of cochlear sensory epithelia was reported as well. These symptoms were associated with significantly shorter lifespan. Coincidental with the onset of FSGS, there was hardly any mtDNA left in the glomerular tufts. These results demonstrate that Mpv17 controls mtDNA copy number by a highly tissue- and possibly cytotype-specific mechanism.

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“…First described by Appenzeller et al 1 in 1976, Navajo neuropathy or neurohepatopathy (NNH) is an autosomal recessive disease affecting full-blooded Navajo children living in southwestern United States. The incidence of NNH is estimated at 1 per 1,600 live births in the western part of the Navajo Reservation, where most of the cases have been reported.…”

mentioning

confidence: 99%