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Retinitis Pigmentosa
Published in K. Gupta, P. Carmichael, A. Zumla, 100 Short Cases for the MRCP, 2020
K. Gupta, P. Carmichael, A. Zumla
Refsum's disease is characterized by peripheral neuropathy, cerebellar ataxia, and elevated cerebrospinal fluid protein without the presence of pleocytosis, deafness and ichthyosis. The condition is inherited as an autosomal recessive trait. Biochemically there is a defective metabolism of phytanic acid that becomes deposited in different tissues of the body including the eyes. There is no satisfactory treatment available. Phytanic acid-free diet and plasma exchange may help in preventing the progression of disease.
Neonatal adrenoleukodystrophy/disorders of peroxisomal biogenesis
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Defective peroxisomal function is manifest in pathways of plasmalogen synthesis, pipecolic acid and phytanic acid metabolism, branched chain fatty acid oxidation and cholesterol metabolism. Plasma levels of VLCFA and bile acid intermediates are elevated. The VLCFA accumulate in this condition and in Zellweger syndrome because of failure to catabolize them [88]. All of the enzymes of peroxisomal β-oxidation are defective. These enzymes are synthesized normally, but they are degraded rapidly because they cannot target into peroxisomes. Cultured fibroblasts of a patient with neonatal ALD have been shown to make mRNA normally for an enzyme of fatty acid oxidation whose activity could not be found in autopsied liver [89].
Retinoids in Keratinization Disorders
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
Refsum syndrome is an autosomal recessive disorder characterized by elevation of phytanic acid, retinal degeneration, peripheral neuropathy, ataxia, and ichthyosis. A multidisciplinary approach for eye and neurologic findings, along with emollients and keratolytic agents for ichthyosis, are needed. A phytanic acid-free diet (phytanic acid consumption ≤10 mg) and plasmapheresis are recommended. Topical therapy, including moisturizing creams, keratolytic agents, and retinoids, should be considered (31,32).
Two siblings with Heimler syndrome caused by PEX1 variants: follow-up of ophthalmologic findings
Published in Ophthalmic Genetics, 2021
Dorien Herijgers, Ellen Denayer, Irina Balikova, Peter Witters, Julie Jacob, Ingele Casteels
Subject 1 has delayed development of gross motor performance since he only started walking at the age of 18 months. According to the parents, his intelligence quotient (IQ)is reported to be below average, but we do not have access to the exact results. He follows special education adapted for children with hearing problems. Biochemical screening for other evidence of peroxisomal dysfunction demonstrated no abnormalities, more specifically the values for pipecolic acid and very-long-chain fatty acid (VLCFA) were normal. Subject 2 has a failure to thrive with weight and height 2 standard deviations (SD) below the mean. Her IQ is reported to be below average but records were not available for review. In contrast to subject 1, biochemical screening for peroxisomal dysfunction revealed increased levels of pipecolic acid (12,3µ/L) and VLCFA (pristanic acid, phytanic acid and C26) which is compatible with peroxisomal dysfunction. These findings are remarkable since most reported patients with Heimler syndrome do not have biochemical evidence of a peroxisome biogenesis disorder (PBD) (3).
Putative adjunct therapies to target mitochondrial dysfunction and oxidative stress in phenylketonuria, lysosomal storage disorders and peroxisomal disorders
Published in Expert Opinion on Orphan Drugs, 2020
Nadia Turton, Tricia Rutherford, Dick Thijssen, Iain P Hargreaves
Evidence of ETC impairment has been associated with the accumulation of VLCFAs in patients with X-ALD [83]. This is a peroxisomal disorder caused by mutations in the ABCD1 gene encoding the ABC peroxisome transporter, which is required for the entry of VLCFAs or VLCFA-CoAs into the organelle [84] (see Figure 3). Deletion of the ABCD1 gene in B12 oligodendrocytes and U87 astrocytes (cellular model of X-ALD pathology) resulted in a reduction in mitochondrial membrane potential, decreased activity of ETC complex I, as well as ATP synthase with an accompanied reduction in cellular ATP levels [83]. Although the mechanism by which VCFLAs impair mitochondrial function remains to be elucidated, fibroblasts from X-ALD patients with excess VLCFA C26:0 reported evidence of mtDNA oxidation together with impaired ETC activity and enhanced ROS production [85]. This study concluded that excess C26:0 disrupts oxidative phosphorylation and induces ETC ROS generation, in particular at complexes I and II. These free radicals can then oxidize mtDNA, which could contribute to a vicious cycle of mitochondrial dysfunction. Accumulated substances in various peroxisome disorders including VLCFA, phytanic acid, and plasmalogens may directly inhibit ETC complex I activity, resulting in upregulated ROS generation [86]. Thus, mitochondrial dysfunction in peroxisome disorders may be a prominent contributor to the increase in OS, implicated in these diseases.
Posterior column ataxia with retinitis pigmentosa (PCARP) in an Iranian patient associated with the FLVCR1 gene
Published in Ophthalmic Genetics, 2020
Fahimeh Beigi, Marta Del Pozo-Valero, Inmaculada Martin-Merida, Mohammad Yahya Vahidi Mehrjardi, Masoud Reza Manaviat, Amir Sherafat, Carmen Ayuso, Nasrin Ghasemi
The differential diagnosis for RP and neurologic degeneration includes Refsum disease, other peroxisomal disorders, beta-lipoproteinemia, neuropathy, ataxia and RP (NARP), rare forms of Charcot–Marie–Tooth, PNPLA6-related disorders, and disorders of copper metabolism. Plasmatic phytanic acid level, vitamin E levels, B12 levels, ceruloplasmin level, cholesterol levels, and plasma lactate levels were all normal. There was no evidence of demyelination, and audiometry was within normal limits distinguishing from Refsum disease or other Zellweger spectrum disorders. Interestingly, despite posterior column neurologic findings on examination (areflexia and reduced proprioception), spinal MRI was within normal limits and no posterior column hyperintensity was observed, as it was previously reported by Puffenberger et al. (7).