Rhizomelic chondrodysplasia punctata ( RCDP ) is a rare disorder of peroxisomal metabolism, with an estimated incidence of 1:100.000. There are 3 genetic subtypes. RCDP type 1, caused by mutations in the PEX7 gene, is the most common type. RCDP type 2 and 3 are single enzyme deficiencies in the plasmalogen biosynthesis pathway.
Clinically the three genetic subtypes are indistinguishable; within each subtype there is a wide variety in severity of the disease.
At the severe end of the spectrum, the disease is characterized by a typical facial appearance, congenital cataracts, rhizomelia, transient periarticular calcifications, arthrogenic contractures, somatic growth impairment and near absence of developmental milestones.
Magnetic Resonance Imaging ( MRI ) of the brain shows both developmental and regressive abnormalities, including delayed meylination, increased ventricular size and subarachnoidal spaces, supratentorial myelin abnormalities, progressive cerebellar atrophy and cervical stenosis.
Life expectancy is dramatically shortened. In patients with the milder variant, skeletal problems are mild.
Mild rhizomelic chondrodysplasia punctata may be suspected when a combination of congenital cataracts and developmental delay is found.
The biochemical hallmarks of RCDP are: 1) decreased concentration of plasmalogens in erythrocytes in all three subtypes and 2) high levels of phytanic acid, which accumulates in an age and diet dependent way in RCDP type 1.
The severity of decreased erythrocyte plasmalogens corresponds with the severity of the disease and abnormalities seen on MRI of the brain.
Since plasmalogens are important constituents of neuronal membranes, it is assumed that the lack of plasmalogens results in abnormal excitatory activity of neurons in the central nervous system ( CNS ) and in abnormal nerve conduction in both the central and peripheral nervous tissue. ( Xagena )
Bams-Mengerink AM et al, Orphanet Journal of Rare Diseases 2013, 8:174