Pain syndromes

Gene: MPV17

I don't know

After discussion with clinical team (Arianna Tucci) it was decided to leave the rating as Amber.

Created: 19 Sep 2017, 11:28 a.m.

Identification of a single missense mutation in patients with NNH confirmed that the disease is probably due to a founder effect, and extended the phenotypic spectrum associated with MPV17 mutations. However, MPV17 has been associated with the hepatocerebral form of mitochondrial DNA depletion syndrome (MDS), a mutation in this protein leads to an mtDNA (mitochondrial DNA) copy number decrease. By 2013, MDS caused by MPV17 mutations had been reported in 32 patients with the clinical manifestations including early progressive liver failure, neurological abnormalities, hypoglycaemia and raised blood lactate [PMID:23714749].In addition, MPV17 mutations have also been associated with autosomal recessive adult-onset neuropathy and leukoencephalopathy with multiple mtDNA deletions in skeletal muscle (PMID:22508010). Thus, MPV17 mutations can lead to recessive MDS or recessive multiple mtDNA deletion disorders. Congenital neuropathy leads to absent pain at birth in severe cases. However hepatic failure and encephalopathy predominates any neuropathy. Possible founder effect, review with clinical team.

Created: 11 Jul 2017, 12:43 p.m.

Comment on list classification: To be reviewed by clinical team regarding the pertinence of this gene

Created: 9 Jul 2017, 5:01 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial DNA depletion syndrome 6 (hepatocerebral type); 256810; Navajo neurohepatopathy; Pain insensitivity

Publications

• 185990
• 11431741
• 16582910
• 16909392
• 23714749
• 22508010

Red List (low evidence)

Marked as red by the expert reviewer Dave Bennett: the overwhelming clinical presentation will be with encephalopathy, hepatic and not as an isolated painful neuropathy.

Created: 19 Sep 2017, 11:02 a.m.

The clinical picture is more of encephalopathy / hepatic failure, rather than neuropathy - hence I would mark it as amber

Created: 13 Jul 2017, 10:04 a.m.