Peroxisomal disorders represent a class of medical conditions caused by defects in
peroxisome
A peroxisome () is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen pero ...
functions.
This may be due to defects in single enzymes
important for peroxisome function or in
peroxin
Peroxins (or peroxisomal/peroxisome biogenesis factors) represent several protein families found in peroxisomes. Deficiencies are associated with several peroxisomal disorders. Peroxins serve several functions including the recognition of c ...
s, proteins encoded by ''PEX'' genes that are critical for normal peroxisome assembly and biogenesis.
Peroxisome biogenesis disorders
Peroxisome biogenesis disorders (PBDs) include the
Zellweger syndrome spectrum (PBD-ZSD) and
rhizomelic chondrodysplasia punctata
Rhizomelic chondrodysplasia punctata is a rare developmental brain disorder characterized by systemic shortening of the proximal bones (i.e. rhizomelia), seizures, recurrent respiratory tract infections and congenital cataracts. The affected indivi ...
type 1 (RCDP1).
PBD-ZSD represents a continuum of disorders including
infantile Refsum disease
Infantile Refsum disease (IRD) is a rare autosomal recessive congenital peroxisomal biogenesis disorder within the Zellweger spectrum. These are disorders of the peroxisomes that are clinically similar to Zellweger syndrome and associated with ...
,
neonatal adrenoleukodystrophy
Neonatal adrenoleukodystrophy is an inborn error of peroxisome biogenesis. It is part of the Zellweger spectrum. It has been linked with multiple genes (at least five) associated with peroxisome biogenesis, and has an autosomal recessive
...
, and
Zellweger syndrome. Collectively, PBDs are autosomal recessive developmental brain disorders that also result in skeletal and craniofacial dysmorphism, liver dysfunction, progressive sensorineural hearing loss, and
retinopathy.
PBD-ZSD is most commonly caused by mutations in the ''PEX1'', ''PEX6'', ''PEX10'', ''PEX12'', and ''PEX26'' genes.
This results in the over-accumulation of
very long chain fatty acids A very-long-chain fatty acid (VLCFA) is a fatty acid with 22 or more carbons. Their biosynthesis occurs in the endoplasmic reticulum. VLCFA's can represent up to a few percent of the total fatty acid content of a cell.
Unlike most fatty acids, VL ...
and branched chain fatty acids, such as
phytanic acid
Phytanic acid (or 3,7,11,15-tetramethyl hexadecanoic acid) is a branched chain fatty acid that humans can obtain through the consumption of dairy products, ruminant animal fats, and certain fish. Western diets are estimated to provide 50–100 ...
. In addition, PBD-ZSD patients show deficient levels of
plasmalogens
Glycerophospholipids of biochemical relevance are divided into three subclasses based on the substitution present at the sn-1 position of the glycerol backbone: acyl, alkyl and alkenyl. Of these, the alkyl and alkenyl moiety in each case form an ...
, ether-phospholipids necessary for normal brain and lung function.
RCDP1 is caused by mutations in the ''PEX7'' gene, which encodes the PTS2 receptor.
RCDP1 patients can develop large tissue stores of branched chain fatty acids, such as
phytanic acid
Phytanic acid (or 3,7,11,15-tetramethyl hexadecanoic acid) is a branched chain fatty acid that humans can obtain through the consumption of dairy products, ruminant animal fats, and certain fish. Western diets are estimated to provide 50–100 ...
, and show reduced levels of
plasmalogens
Glycerophospholipids of biochemical relevance are divided into three subclasses based on the substitution present at the sn-1 position of the glycerol backbone: acyl, alkyl and alkenyl. Of these, the alkyl and alkenyl moiety in each case form an ...
.
Enzyme and transporter defects
Peroxisomal disorders also include:
References
External links
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{{Peroxisomal disorders
Peroxisomal disorders
Organelles