Variant rhizomelic chondrodysplasia punctata (RCDP) with normal plasma phytanic acid: Clinico-biochemical delineation of a subtype and complementation studies

Barth, P. G.; Wanders, Ronald J. A.; Schutgens, R. B. H.; Staalman, C. R.

doi:10.1002/(sici)1096-8628(19960315)62:2<164::aid-ajmg9>3.0.co;2-w

Cited by 24 publications

(14 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patient 9, diagnosed at age 9, had only slightly distinctive features, bilateral cataracts, mild shortening of the femora, and a decreased range of motion of the hips. 4 She was able to express telegram-style sentences and walked independently at home. At a chronologic age of 10, her mental age was between 1 and 2 years.…”

Section: Resultsmentioning

confidence: 64%

“…1 The finding of decreased erythrocyte plasmalogen levels 2,3 and increased plasma phytanic acid levels 3 established RCDP as a genetic peroxisomal disorder and enabled the identification of milder phenotypes. 4,5 It also allowed differentiation between the milder forms of the peroxisomal RCDP and the nonrhizomelic forms of chondrodysplasia punctata, including Conradi-Hü nermann syndrome.…”

mentioning

confidence: 99%

See 1 more Smart Citation

MRI of the brain and cervical spinal cord in rhizomelic chondrodysplasia punctata

Bams-Mengerink

Majoie²,

Durán³

et al. 2006

Neurology

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 64%

mentioning

confidence: 99%

MRI of the brain and cervical spinal cord in rhizomelic chondrodysplasia punctata

Bams-Mengerink

Majoie²,

Durán³

et al. 2006

Neurology

View full text Add to dashboard Cite

show abstract

“…Decay in neurologic skills is not typical, although interaction with the surrounding is less in periods of illness and frequent seizures [15]. Less is known about the disease course of patients with the milder phenotype of the disorder [4,6,16,17]. In this cohort, 4 patients with the milder clinical and biochemical phenotype are represented.…”

Section: Discussionmentioning

confidence: 99%

“…RCDP type 2 (OMIM 222765) and 3 (OMIM 600121) are single enzyme deficiencies in the plasmalogen biosynthesis pathway [3]. Clinically the 3 genetic subtypes are indistinguishable; within each subtype there is a wide variety in severity of the disease [4]. 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 (Figure 1) [5].…”

Section: Introductionmentioning

confidence: 99%

The neurology of rhizomelic chondrodysplasia punctata

Bams-Mengerink

Koelman

Waterham

et al. 2013

Orphanet J Rare Dis

View full text Add to dashboard Cite

BackgroundTo describe the neurologic profiles of Rhizomelic chondrodysplasia punctata (RCDP); a peroxisomal disorder clinically characterized by skeletal abnormalities, congenital cataracts, severe growth and developmental impairments and immobility of joints. Defective plasmalogen biosynthesis is the main biochemical feature.MethodsObservational study including review of clinical and biochemical abnormalities, genotype, presence of seizures and neurophysiological studies of a cohort of 16 patients with RCDP.ResultsPatients with the severe phenotype nearly failed to achieve any motor or cognitive skills, whereas patients with the milder phenotype had profound intellectual disability but were able to walk and had verbal communication skills. Eighty-eight percent of patients developed epileptic seizures. The age of onset paralleled the severity of the clinical and biochemical phenotype. Myoclonic jerks, followed by atypical absences were most frequently observed. All patients with clinical seizures had interictal encephalographic evidence of epilepsy. Visual evoked (VEP) and brain auditory potential (BAEP) studies showed initial normal latency times in 93% of patients. Deterioration of VEP occurred in a minority in both the severe and the milder phenotype. BAEP and somatosensory evoked potentials (SSEP) were more likely to become abnormal in the severe phenotype. Plasmalogens were deficient in all patients. In the milder phenotype levels of plasmalogens were significantly higher in erythrocytes than in the severe phenotype. Phytanic acid levels ranged from normal to severely increased, but had no relation with the neurological phenotype.ConclusionNeurodevelopmental deficits and age-related occurrence of seizures are characteristic of RCDP and are related to the rest-activity in plasmalogen biosynthesis. Evoked potential studies are more likely to become abnormal in the severe phenotype, but are of no predictive value in single cases of RCDP.

show abstract

“…In addition, a number of patients with a milder phenotypic variant of RCDP type 1 have been described, but all followed a classical presentation, with differences in degree of cognitive impairment, longer life expectancy, and lack of rhizomelia or chondrodysplasia (Poll-The et al 1991;Smeitink et al 1992;Barth et al 1996). These patients all have been diagnosed with RCDP type 1 early in life, whereas the patients we describe here were diagnosed with classical RD in adulthood.…”

Section: Figurementioning

confidence: 99%

Identification of PEX7 as the Second Gene Involved in Refsum Disease

Brink

Brites

Haasjes

et al. 2003

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Patients affected with Refsum disease (RD) have elevated levels of phytanic acid due to a deficiency of the peroxisomal enzyme phytanoyl-CoA hydroxylase (PhyH). In most patients with RD, disease-causing mutations in the PHYH gene have been identified, but, in a subset, no mutations could be found, indicating that the condition is genetically heterogeneous. Linkage analysis of a few patients diagnosed with RD, but without mutations in PHYH, suggested a second locus on chromosome 6q22-24. This region includes the PEX7 gene, which codes for the peroxin 7 receptor protein required for peroxisomal import of proteins containing a peroxisomal targeting signal type 2. Mutations in PEX7 normally cause rhizomelic chondrodysplasia punctata type 1, a severe peroxisomal disorder. Biochemical analyses of the patients with RD revealed defects not only in phytanic acid a-oxidation but also in plasmalogen synthesis and peroxisomal thiolase. Furthermore, we identified mutations in the PEX7 gene. Our data show that mutations in the PEX7 gene may result in a broad clinical spectrum ranging from severe rhizomelic chondrodysplasia punctata to relatively mild RD and that clinical diagnosis of conditions involving retinitis pigmentosa, ataxia, and polyneuropathy may require a full screen of peroxisomal functions.

show abstract

Variant rhizomelic chondrodysplasia punctata (RCDP) with normal plasma phytanic acid: Clinico-biochemical delineation of a subtype and complementation studies

Cited by 24 publications

References 23 publications

MRI of the brain and cervical spinal cord in rhizomelic chondrodysplasia punctata

MRI of the brain and cervical spinal cord in rhizomelic chondrodysplasia punctata

The neurology of rhizomelic chondrodysplasia punctata

Identification of PEX7 as the Second Gene Involved in Refsum Disease

Contact Info

Product

Resources

About