PEX7related

PEX7-related refers to a group of disorders caused by biallelic mutations in the PEX7 gene, which encodes the cytosolic receptor for peroxisomal targeting signal type 2 (PTS2). This receptor is essential for the import of a subset of peroxisomal matrix enzymes into the peroxisome. In humans, PTS2 proteins include phytanoyl-CoA hydroxylase and alpha-methylacyl-CoA racemase, among others. Loss of PEX7 function disrupts PTS2 import, leading to mislocalization of these enzymes, impaired peroxisomal beta-oxidation, and disturbed lipid metabolism. Biochemically, PEX7-related disorders often present with elevated very long-chain fatty acids, abnormal levels of phytanic and pristanic acids, and reduced plasmalogen levels in erythrocytes and other tissues.

PEX7-related disorders are most prominently represented by Rhizomelic Chondrodysplasia Punctata type 1 (RCDP1). RCDP1 is a rare autosomal recessive condition characterized by rhizomelic limb shortening, distinctive facial features, cataracts, growth retardation, and hypotonia; severity varies among individuals. Other manifestations may include skeletal anomalies, joint contractures, skin and dental abnormalities, and developmental delay.

Diagnosis typically starts with biochemical screening showing increased phytanic acid and elevated very long-chain fatty acids with decreased plasmalogens, followed by molecular genetic testing to confirm PEX7 mutations. Management is supportive and multidisciplinary, emphasizing physical and orthopedic therapy, vision and hearing monitoring, and nutritional support. There is no cure for PEX7-related disorders, and prognosis depends on the specific mutation and clinical severity. Genetic counseling is recommended due to the autosomal recessive inheritance pattern.