Highlights
- •In-depth review of neuropathy characteristics in PHARC syndrome
- •PHARC syndrome can be expressed as a typical demyelinating CMT for years.
- •Consider PHARC in demyelinating polyneuropathy with hearing loss and retinopathy
Abstract
PHARC (Polyneuropathy, Hearing loss, Ataxia, Retinitis pigmentosa and Cataracts) (MIM#
612674) is an autosomal recessive neurodegenerative disease caused by mutations in the ABHD12 gene. We evaluated two Spanish siblings affected with pes cavus, sensorimotor neuropathy,
hearing loss, retinitis pigmentosa and juvenile cataracts in whom the genetic test
of ABHD12 revealed a novel homozygous frameshift mutation, c.211_223del (p.Arg71Tyrfs*26).
The earliest clinical manifestation in these patients was a demyelinating neuropathy
manifested with a Charcot-Marie-Tooth phenotype over three decades. Progressive hearing
loss, cataracts and retinitis pigmentosa appeared after the age of 30. We herein describe
the complete clinical picture of these two patients, and focus particularly on neuropathy
characteristics. This study supports the fact that although PHARC is rare, its phenotype
is very characteristic and we should include its study in patients affected with demyelinating
polyneuropathy, hearing loss and retinopathy.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of the Neurological SciencesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- A novel Refsum-like disorder that maps to chromosome 20.Neurology. 2009; 72: 20-27
- Mutations in ABHD12 cause the neurodegenerative disease PHARC: an inborn error of endocannabinoid metabolism.Am. J. Hum. Genet. 2010; 87: 410-417
- Exome sequencing extends the phenotypic Spectrum for ABHD12 mutations from syndromic to nonsyndromic retinal degeneration.Ophthalmology. 2014; 121: 1620-1627
- Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3.Orphanet. J. Rare Dis. 2012; 7: 59
- Novel ABHD12 mutations in PHARC patients.Ann. Otol. Rhinol. Laryngol. 2015; 124: 77S-83S
- A complex homozygous mutation in ABHD12 responsible for PHARC syndrome discovered with NGS and review of the literature.J. Peripher. Nerv. Syst. 2017; 22: 77-84
- Diagnosis, natural history, and management of Charcot-Marie-Tooth disease.Lancet Neurol. 2009; 8: 654-667
- Charcot-Marie-Tooth disease: genetic and clinical spectrum in a Spanish clinical series.Neurology. 2013; 81: 1617-1625
- Audiological findings in Charcot–Marie–Tooth disease type 4C.J. Int. Adv. Otol. 2017; 13: 93-99
- Mutations in PRPS1, which encodes the phosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis, cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (cmtx5).Am. J. Hum. Genet. 2007 Sep; 81: 552-558
- Heredoataxia hemeralopica polyneuritiformis.Nord. Med. 1945; 28: 2682-2685
- Refsum disease.in: Adam M.P. Ardinger H.H. Pagon R.A. Wallace S.E. LJH Bean Mefford H.C. GeneReviews. Seattle (WA). 1993
- Differential diagnosis of Charcot-Marie-Tooth disease and related neuropathies.Neurol. Sci. 2004; 25: 72-82
- A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol.Chem. Biol. 2007 Dec; 14: 1347-1356
- Biochemical and pharmacological characterization of human α/β-hydrolase domain containing 6 (ABHD6) and 12 (ABHD12).J. Lipid Res. Nov 12, 2012; 53 (Internet). Available from:: 2413-2424
- ABHD12 controls brain lysophosphatidylserine pathways that are deregulated in a murine model of the neurodegenerative disease PHARC.Proc. Natl. Acad. Sci. 2013; 110: 1500-1505
- Functional validation of ABHD12 mutations in the neurodegenerative disease PHARC.Neurobiol. Dis. 2017; 98: 36-51
Article info
Publication history
Published online: February 07, 2018
Accepted:
February 6,
2018
Received in revised form:
January 19,
2018
Received:
November 7,
2017
Identification
Copyright
© 2018 Elsevier B.V. All rights reserved.
