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As a result of impaired [[peroxisome]] function, an individual's tissues and cells can accumulate very long chain fatty acids (VLCFA) and branched chain fatty acids (BCFA) that are normally degraded in [[peroxisomes]]. The accumulation of these lipids can impair the normal function of multiple organ systems, as discussed below. In addition, these individuals can show deficient levels of [[plasmalogens]], ether-phospholipids that are especially important for brain, lung, and heart functions.
As a result of impaired [[peroxisome]] function, an individual's tissues and cells can accumulate very long chain fatty acids (VLCFA) and branched chain fatty acids (BCFA) that are normally degraded in [[peroxisomes]]. The accumulation of these lipids can impair the normal function of multiple organ systems, as discussed below. In addition, these individuals can show deficient levels of [[plasmalogens]], ether-phospholipids that are especially important for brain, lung, and heart functions.

== Clinical manifestations of disease ==
Infantile Refsum disease is one of three [[peroxisome biogenesis disorders]] which belong to the Zellweger spectrum of peroxisome biogenesis disorders (PBD-ZSD).<ref name="pmid17055079">{{Cite journal | last1 = Steinberg | first1 = S. | last2 = Dodt | first2 = G. | last3 = Raymond | first3 = G. | last4 = Braverman | first4 = N. | last5 = Moser | first5 = A. | last6 = Moser | first6 = H. | title = Peroxisome biogenesis disorders | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | volume = 1763 | issue = 12 | pages = 1733–48 | year = 2006 | doi = 10.1016/j.bbamcr.2006.09.010 | pmid=17055079}}</ref> The other two disorders are [[Zellweger syndrome]] (ZS) and [[neonatal adrenoleukodystrophy]] (NALD).<ref>[http://www.genetests.org/query?dz=pbd GeneReviews: Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum<!-- Bot generated title -->]</ref><ref name="pmid17041890">{{Cite journal | last1 = Krause | first1 = C. | last2 = Rosewich | first2 = H. | last3 = Thanos | first3 = M. | last4 = Gärtner | first4 = J. | title = Identification of novel mutations inPEX2,PEX6,PEX10,PEX12, andPEX13in Zellweger spectrum patients | journal = Human Mutation | volume = 27 | issue = 11 | pages = 1157 | year = 2006 | doi = 10.1002/humu.9462 | pmid=17041890}}</ref> Although they share a similar molecular basis for disease, Infantile Refsum disease is less severe than [[Zellweger syndrome]].<ref name="doi10.1007/978-0-387-30378-9_26">{{Cite book | last1 = Raymond | first1 = G. V. | last2 = Watkins | first2 = P. | last3 = Steinberg | first3 = S. | last4 = Powers | first4 = J. | chapter = Peroxisomal Disorders | title = Handbook of Neurochemistry and Molecular Neurobiology | pages = 631–670 | year = 2009 | isbn = 978-0-387-30345-1 | doi = 10.1007/978-0-387-30378-9_26}}</ref>

Infantile Refsum disease is a developmental brain disorder.<ref name="pmid17055079"/> In addition, patients can show a reduction in [[central nervous system]] (CNS) [[myelin]] (particularly cerebral), which is referred to as (hypomyelination). Myelin is critical for normal CNS functions. Patients can also show postdevelopmental sensorineuronal degeneration that leads to a progressive loss of hearing and vision.<ref name="pmid17055079"/>

Infantile Refsum disease can also affect the function of many other organ systems. Patients can show craniofacial abnormalities, [[hepatomegaly]] (enlarged liver), and progressive adrenal dysfunction.<ref name="pmid17055079"/><ref name="doi10.1007/978-0-387-30378-9_26"/> Newborns may present with profound [[hypotonia]] (low muscle tone), and a poor ability to feed.<ref name="pmid17055079"/><ref name="doi10.1007/978-0-387-30378-9_26"/> In some patients, a progressive [[leukodystrophy]] has been observed that has a variable age of onset.<ref name="doi10.1007/978-0-387-30378-9_26"/>


== Molecular diagnostics ==
== Molecular diagnostics ==

Revision as of 12:49, 31 December 2016

Infantile Refsum disease

Infantile Refsum disease (IRD), also called infantile phytanic acid storage disease,[1] is a rare autosomal recessive[2] congenital peroxisomal biogenesis disorder within the Zellweger spectrum. These are disorders of the peroxisomes that are clinically similar to Zellweger syndrome and associated with mutations in the PEX family of genes.[3][4] IRD is associated with deficient phytanic acid catabolism, as is Adult Refsum disease, but they are different disorders that should not be confused.[1][5]

Molecular basis of disease

Infantile Refsum disease is an autosomal recessive disorder caused by mutations in genes that encode peroxins, proteins required for normal peroxisome assembly. Most commonly, patients have mutations in the PEX1, PEX3, PEX6, PEX12, and PEX26 genes.[6] In almost all cases, patients have mutations that inactivate or greatly reduce the activity of both the maternal and paternal copies of one these aforementioned PEX genes.

As a result of impaired peroxisome function, an individual's tissues and cells can accumulate very long chain fatty acids (VLCFA) and branched chain fatty acids (BCFA) that are normally degraded in peroxisomes. The accumulation of these lipids can impair the normal function of multiple organ systems, as discussed below. In addition, these individuals can show deficient levels of plasmalogens, ether-phospholipids that are especially important for brain, lung, and heart functions.

Molecular diagnostics

In addition to genetic tests involving PEX genes,[7][8] biochemical tests have proven highly effective for the diagnosis of infantile Refsum disease and other peroxisomal disorders. Typically, IRD patients show elevated very long chain fatty acids in their blood plasma. Cultured primarily skin fibroblasts obtained from patients show elevated very long chain fatty acids, impaired very long chain fatty acid beta-oxidation, phytanic acid alpha-oxidation, pristanic acid alpha-oxidation, and plasmalogen biosynthesis.[9]

Prognosis

Currently, there is no cure for infantile Refsum disease syndrome, nor is there a standard course of treatment. Infections should be guarded against to prevent such complications as pneumonia and respiratory distress. Other treatment is symptomatic and supportive. Patients show variable lifespans with some individuals surviving until adulthood and into old age.[10]

Additional resources for patients and families

  • European Leukodystrophy Foundation[11]
  • March of Dimes Foundation[12]
  • The Global Foundation for Peroxisomal Disorders[13]
  • United Leukodystrophy Foundation[14]
  • Zellwegers Support Network[15]

External links

References

  1. ^ a b Online Mendelian Inheritance in Man (OMIM): 266510
  2. ^ Choksi, V; Hoeffner, E; Karaarslan, E; Yalcinkaya, C; Cakirer, S (2003). "Infantile refsum disease: case report". AJNR. American journal of neuroradiology. 24 (10): 2082–4. PMID 14625237.
  3. ^ Steinberg, S.; Raymond, G.; Braverman, N.; Moser, A.; Pagon, H.; Adam, R.; Bird, T.; Dolan, C.; Fong, K.; Stephens, K. (1993). "Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum". PMID 20301621. {{cite journal}}: Cite journal requires |journal= (help)
  4. ^ Krause, C.; Rosewich, H.; Gärtner, J. (2009). "Rational diagnostic strategy for Zellweger syndrome spectrum patients". European Journal of Human Genetics. 17 (6): 741–748. doi:10.1038/ejhg.2008.252. PMC 2947092. PMID 19142205.
  5. ^ Online Mendelian Inheritance in Man (OMIM): 266500
  6. ^ Online Mendelian Inheritance in Man (OMIM): REFSUM DISEASE, INFANTILE FORM - 266510
  7. ^ Steinberg, S.; Chen, L.; Wei, L.; Moser, A.; Moser, H.; Cutting, G.; Braverman, N. (2004). "The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum". Molecular Genetics and Metabolism. 83 (3): 252–263. doi:10.1016/j.ymgme.2004.08.008. PMID 15542397.
  8. ^ Yik, W. Y.; Steinberg, S. J.; Moser, A. B.; Moser, H. W.; Hacia, J. G. (2009). "Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders". Human Mutation. 30 (3): E467–E480. doi:10.1002/humu.20932. PMC 2649967. PMID 19105186.
  9. ^ Cite error: The named reference pmid17055079 was invoked but never defined (see the help page).
  10. ^ Cite error: The named reference doi10.1007/978-0-387-30378-9_26 was invoked but never defined (see the help page).
  11. ^ http://www.ela-asso.com/?q=node/&lang=en&force=1
  12. ^ http://www.marchofdimes.org/
  13. ^ http://www.thegfpd.org/
  14. ^ http://www.ulf.org/
  15. ^ https://www.facebook.com/home.php?sk=group_125397297528689
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