1/17. A novel nonsense mutation of the PEX7 gene in a patient with rhizomelic chondrodysplasia punctata. Mutations in the PEX7 gene encoding a peroxisome targeting signal 2 (PTS2) were identified in two patients with rhizomelic chondrodysplasia punctata (RCDP). A 7-year-old girl, the first Japanese individual to be diagnosed biochemically as a case of RCDP, had a novel nonsense mutation, R232ter, in the PEX7 gene, which had been inherited from her consanguineous parents. Another patient, a Chilean boy with RCDP, had compound heterozygous mutations of PEX7, L292ter and A218V, both of which have been documented. R232ter, which deletes all of the last two WP40 repeats in the PEX7 gene, is sufficient to inactivate functions of the PEX7 gene. ( info) |
2/17. prenatal diagnosis of rhizomelic chondrodysplasia punctata due to isolated alkyldihydroacetonephosphate acyltransferase synthase deficiency. Current practices in prenatal diagnosis of rhizomelic chondrodysplasia punctata (RCDP) are reviewed. A case is presented with a family having one daughter affected with RCDP due to alkyldihydroacetonephosphate acyltransferase synthase (DHAPAT synthase) deficiency, and three subsequent pregnancies. Biochemical test values are presented for the pregnancies and daughter. Post-mortem tests of one fetus of a terminated pregnancy showed that radiologic examination could not make the diagnosis of RCDP. We conclude that biochemical or molecular testing is necessary to accurately diagnose this type of RCDP prenatally. ( info) |
| Cerebellar atrophy, consequent to the postdevelopmental degeneration and loss of purkinje cells and granular neurons, has been identified in three patients with rhizomelic chondrodysplasia punctata (RCDP). Cerebellar atrophy in our two chronic patients was symmetrical, but the vermis and medial portions of both hemispheres, particularly the dorsal lobules, displayed more severe atrophy than the lateral hemispheres. The distal tips of folia showed the greatest neuronal loss. Residual purkinje cells showed progressive degenerative changes that appeared to be due, in part, to their topography. The precise mode of death of purkinje cells in RCDP has not been established, but it does not appear to be mediated by entrance into the cell cycle or by ubiquitination; however, alterations in intracellular calcium levels and mitochondria may be involved. Elevated serum/CSF phytanic acid, decreased levels of tissue plasmalogens and increased chronological age are believed to play synergistic pathogenetic roles in this lesion. ( info) |
4/17. Abnormal myelin formation in rhizomelic chondrodysplasia punctata type 2 (DHAPAT-deficiency). The case of a Yemeni girl with isolated peroxisomal acyl-CoA:dihydroxyacetonephosphate acyltransferase (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. ( info) |
| We present a male autopsied case of chondrodysplasia punctata with abnormal face, symmetrical proximal limb shortness, severe psychomotor developmental delay, respiratory muscle weakness, and death at the age of 2 years. Although his clinical manifestations were similar to those of rhizomelic chondrodysplasia punctata (RCDP), biochemical studies using skin fibroblasts did not document the peroxisomal dysfunction described in RCDP. In addition, the sterol profile, for which abnormalities have recently been reported in cases of X-linked dominant form chondrodysplasia punctata (CDPX2), was normal both in the liver and in the fibroblasts. This patient may represent a new lethal form of chondrodysplasia punctata. ( info) |
| Rhizomelic chondrodysplasia punctata (RCDP) is a rare peroxisomal disorder leading to multiple developmental malformations, including skeletal deformity. Specifically, involvement of the vertebral bodies has been described. Presented here is a case of a two-year-old female child with RCDP leading to advanced cervical stenosis as detected on magnetic resonance imaging (MRI) studies of the cervical spine. The practicing clinician should be aware of the possibility of cervical stenosis secondary to RCDP and its impact on the management of the patient with this rare disease process. copyright Wiley-Liss. Inc. ( info) |
7/17. MR imaging and MR spectroscopy in rhizomelic chondrodysplasia punctata. A case of rhizomelic chondrodysplasia punctata was investigated with MR imaging of the brain and hydrogen-1 MR spectroscopy of the brain and blood. Areas with abnormal signal hyperintensity on T2-weighted images or hypointensity on T1-weighted images were detected in the subcortical white matter. MR spectroscopy of the brain showed that normal-appearing white matter was characterized by increased levels of mobile lipids and myo-inositol, reduced levels of choline, and the presence of acetate. The importance of these metabolic anomalies is correlated to the deficiency in plasmalogen biosynthesis. ( info) |
8/17. Lethal non-rhizomelic dysplasia epiphysealis punctata. We describe two new cases of a rare form of lethal chondrodysplasia punctata (so-called X-linked dominant, non-rhizomelic form), a condition characterized by widespread multicentric stippled calcifications of the cartilaginous parts of the long bones, spine, ribs and flat bones. The mother of one of the patients had bone dysplasia consistent with the X-linked dominant form of chondrodysplasia punctata. We suggest that a skeletal survey, including lateral view of the spine, together with biochemical studies of peroxisomal status are indicated in all newborns with severe, unusual forms of chondrodysplasia punctata. In this way, accurate categorization of the lethal, non-rhizomelic types of this condition will be facilitated. ( info) |
9/17. Delayed myelination in a rhizomelic chondrodysplasia punctata case: MR spectroscopy findings. Rhizomelic chondrodysplasia punctata is a member of genetic peroxisomal disorders. Delayed myelination, which is probably related to the inadequacy of plasmalogens biosynthesis, is an important feature of this disorder. Direct assessment of neuropathologic aspects of RCDP syndrome such as neuronal degeneration and delayed myelination is possible with MR spectroscopy.In this report, MR spectroscopy findings (decreased Cho/Cr and increased Ins-Gly/Cr ratios and increased levels of mobile lipids) of a rhizomelic chondrodysplasia punctata case supporting delayed myelination are presented. This is the second report of MR spectroscopy examination of the specific brain metabolic changes associated with rhizomelic chondrodysplasia punctata. ( info) |
10/17. Prenatal ultrasonographic diagnosis of rhizomelic chondrodysplasia punctata by detection of rhizomelic shortening and bilateral cataracts. Antenatal sonographic diagnosis of rhizomelic chondrodysplasia punctata depends on recognization of the combination of rhizomelic bone shortening and epiphyseal stippling. This is the only report of prenatal ultrasonographic diagnosis of bilateral cataracts in a fetus with rhizomelic chondrodysplasia punctata (type 1). Also, this is the first report of severe rhizomelic limb shortening, and bilateral cataracts prior to the recognization of epiphyseal stippling. ( info) |