Abnormal myelin formation in rhizomelic chondrodysplasia punctata type 2 (DHAPAT‐deficiency)

Abstract

The case of a Yemeni girl with isolated peroxisomal acyl‐CoA:dihydroxyacetonephosphateacyltransferase (DHAPAT) deficiency is reported. She had rhizomelic chondrodysplasia punctata, microcephaly, failure to thrive, delayed motor and mental development, and spastic quadriplegia. Deficient de novo plasmalogen synthesis in her fibroblasts as a result of low DHAPAT activity was found, while her very‐long‐chain fatty acid profile, phytanic acid concentration, alkyl‐dihydroxyacetonephosphate synthase (alkyl‐DHAP synthase) activity, and peroxisomal 3‐ketoacyl‐CoA thiolase protein were normal. A mutation in her DHAPAT complementary DNA resulted in the substitution of an arginine residue in the protein at position 211 by a histidine (R211H). Magnetic resonance imaging showed abnormal white matter signal in the centrum semiovale involving the arcuate fibers, while the corpus callosum was normal. DHAPAT and alkyl‐DHAP synthase initiate the synthesis of plasmalogens, which are major constituents of myelin phospholipids. The reported girl's abnormal formation of myelin is probably related to the inadequacy of plasmalogen biosynthesis, which is likely to be due to deficient DHAPAT activity.

From peroxisomal disorders to common neurodegenerative diseases – the role of ether phospholipids in the nervous system

“…Main pathologic features commonly described in severe RCDP cases include myelination deficits, enlarged ventricles and subarachnoidal spaces, and cerebellar atrophy. White matter signal abnormalities, indicating myelin deficiency, have been detected by magnetic resonance imaging in different brain regions and often involve the parieto‐occipital region . The exact origin of impaired myelination is largely unclear.…”

Peroxisomal Disorders: A Review on Cerebellar Pathologies

“…The onset of cerebellar deterioration was delayed by 1 year in patients with residual albeit very low plasmalogen levels . Non‐inflammatory myelin abnormalities were frequently observed and dysplastic olives and cerebellar heterotaxias noted in post‐mortem studies may refer to developmental defects . The achievement of motor skills in patients with the severe phenotype is poor .…”

Predicted mouse peroxisome-targeted proteins and their actual subcellular locations

“…Peroxisomes are ubiquitous intracellular organelles that originate from the endoplasmatic reticulum [ 1 ]. Various biosynthesis and metabolic pathways including β-oxidation of very long chain fatty acids, α-oxidation of branched and straight chain fatty acids [ 2 ], plasmalogen synthesis [ 3 ], and hydrogen peroxide detoxification [ 4 ] are located in peroxisomes. Unlike mitochondria, peroxisomes lack the ability to synthesize DNA and proteins.…”