Genetics and Refsum disease

Refsum disease is inherited as a recessive trait.

Source: NCBI, Genes and Disease (NCBI/NIH)1

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Back to: « Refsum disease

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In 1997 the gene for Refsum disease was identified and mapped to chromosome 10. The protein product of the gene, PAHX, is an enzyme that is required for the metabolism of phytanic acid. Refsum disease patients have impaired PAHX - phytanic acid hydrolase.

It is thought that Refsum disease is a peroxisomal disorder, since human PAHX contains PTS2 localization sequences, which target it to the peroxisome.

Source: NCBI, Genes and Disease (NCBI/NIH)2

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Genetic Changes

More than 90 percent of all cases of Refsum disease result from mutations in the PHYH gene. The remaining cases are caused by mutations in a gene called PEX7 .

The signs and symptoms of Refsum disease result from the abnormal buildup of a type of fatty acid called phytanic acid. This substance is obtained from the diet, particularly from beef and dairy products. It is normally broken down through a process called alpha-oxidation, which occurs in cell structures called peroxisomes . These sac-like compartments contain enzymes that process many different substances, such as fatty acids and certain toxic compounds.

Mutations in either the PHYH or PEX7 gene disrupt the usual functions of peroxisomes, including the breakdown of phytanic acid. As a result, this substance builds up in the body's tissues. The accumulation of phytanic acid is toxic to cells, although it is unclear how an excess of this substance affects vision and smell and causes the other specific features of Refsum disease .

Source: GHR (NLM/NIH)3

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Inheritance Pattern

This condition is inherited in an autosomal recessive pattern , which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Source: GHR (NLM/NIH)4

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Learn more about the genes associated with Refsum disease

  • PEX7
  • PHYH

Source: GHR (NLM/NIH)5

Inheritance of Refsum disease

Genetic and familial features of the condition may include:6 Genetics of Refsum Disease:

  • Autosomal recessive inheritance

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  1. Source: NCBI, Genes and Disease (NCBI/NIH): books/ NBK22208/ 
  2. ibid.
  3. Source: GHR (NLM/NIH): condition/ refsum-disease
  4. ibid.
  5. ibid.
  6. Source: Human Phenotype Ontology

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