Rhizomelic chondrodysplasia punctata (RCDP) is a genetic disorder which is clinically characterized by rhizomelic shortening of the upper extremities, dysmorphic facial features, congenital contractures and severe growth and mental retardation. Alpha-oxidation of phytanic acid and plasmalogen synthesis that takes place in the peroxisomes are impaired in patients with RCDP. However, a significant biochemical heterogeneity within RCDP has been established recently. Clinical heterogeneity has also been observed among many patients.
Based on the associated mutations, five types of RCDP (RCDP1-5) have been identified. RCDP2 (Rhizomelic chondrodysplasia punctata type 2) is associated with mutations in GNPAT gene. Consequently, patients with RCDP2 have acyl-CoA:dihydroxyacetonephosphate acyltransferase (DHAPAT) deficiency, which in turn disrupts plasmalogen synthesis.
Moammar et al. (2010) reviewed all patients diagnosed with inborn errors of metabolism (IEM) from 1983 to 2008 at Saudi Aramco medical facilities in the Eastern province of Saudi Arabia. During the study period, 165530 Saudi infants were born, of whom a total of 248 newborns were diagnosed with 55 IEM. Affected patients were evaluated based on clinical manifestations or family history of similar illness and/or unexplained neonatal deaths. Almost all patients were born to consanguineous parents. Organelle disorders were found in 18 out of 248 of diagnosed subjects. Among them, a single case from was found to have DHAPAT deficiency with an estimated incidence of 1 per 100,000 live births. The authors concluded that data obtained from this study underestimate the true figures of various IEM in the region. Therefore, there is an urgent need for centralized newborn screening program that utilizes tandem mass spectrometry, and offers genetic counseling for these families.
Sztriha et al. (1997) described the cranial magnetic resonance imaging findings in three siblings with nonrhizomelic chondrodysplasia punctata due to isolated dihydroxyacetonephosphate acyltransferase (DHAPAT) deficiency. Areas of high signal intensity in a patchy distribution on the T2-weighted images were detected in the centrum semiovale in the eldest patient (a 6-year-old girl). The white matter of the second child (a 5-year-old boy) was spared, whereas the youngest sibling (a 2-year-old boy) manifested very severe white matter abnormalities.
[See also: Yemen > Sztriha et al., 2000].
Sztriha et al. (2000) reported a Yemeni girl with isolated peroxisomal acyl-CoA:dihydroxyacetonephosphate acyltransferase (DHAPAT) deficiency. She was born at term after an uneventful pregnancy, labor, and delivery to consanguineous parents. The girl had dysmorphic features, including upslanting palpebral fissures, depressed nasal bridge, long philtrum, thin upper lip, short neck, and disproportionately short proximal segments of the limbs (rhizomelia). The girl's chromosomal analysis was normal and a screen for TORCH (toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex) was negative. Bone X-ray confirmed rhizomelia and revealed punctuate calcification in the femoral and tibial epiphyses. The bone abnormalities were highly suggestive of a peroxisomal disorder. In addition, she had rhizomelic chondrodysplasia punctata, microcephaly, failure to thrive, delayed motor and mental development, and spastic quadriplegia. Magnetic resonance imaging showed abnormal white matter signal in the centrum semiovale involving the arcuate fibers, while the corpus callosum was normal. 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.