Natural history of rhizomelic chondrodysplasia punctata

Abstract

Rhizomelic chondrodysplasia punctata (RCP) is a rare autosomal recessive disorder with many associated medical complications. Prior to this study, natural history information about RCP was limited and based on experiences with small populations of affected individuals. We delineate the natural history of RCP through systematic analysis of 35 previously unreported individuals (as well as review of 62 literature cases with respect to survival and cause of death). Survival, growth, and developmental expectations and medical needs are summarized based upon experience with this population. Survival is greater among this population than previously reported, with 90% surviving up to 1 year and 50% surviving up to 6 years. Cause of death is most often respiratory problem. All infants with RCP have joint contractures, bilateral cataracts, and severe growth and psychomotor delays. Recommendations for health supervision of children with RCP and for parental counseling are presented. ß 2003 Wiley-Liss, Inc.KEY WORDS: bone dysplasia; osteochondrodysplasia; peroxisomal disorders; anticipatory care; guidelines for care INTRODUCTIONRhizomelic chondrodysplasia punctata (RCP) is a rare autosomal recessive disorder of peroxisome metabolism previously said to be inevitably lethal in infancy [Spranger et al., 1971;Heselson et al., 1978, Heymans et al., 1985. It is a panethnic disorder that affects about 1 in 100,000 individuals [Stoll et al., 1989]. As first described by Spranger et al. [1971], the clinical diagnostic characteristics of RCP include severe and symmetrical shortening of the proximal long bones (rhizomelia), bilateral cataracts, and severe growth and psychomotor delays. In addition to rhizomelia, clinical evidence of congenital contractures and typical dysmorphic facial characteristics and radiographic evidence of stippled epiphyses and vertebral coronal clefts can also be diagnostic.Biochemical analyses and complementation studies allow division of individuals with RCP into three types. Those with homozygous or compound heterozygous mutations in the PEX7 gene that encodes peroxin 7 comprise the largest group, classical RCP type 1 [Braverman et al., 1997;Motley et al., 1997;Purdue et al., 1997]. The spectrum of PEX7 mutations has been studied, and functional analysis of mutations demonstrates a direct correlation between PEX7allele activity and the severity of RCP [Motley et al., 2002]. RCP type 2 arises secondary to mutations in the acyl-CoA:dihydroxyacetonephosphate acyltransferase (DHAPAT) gene [Thai et al., 1997;Ofman et al., 1998], and RCP type 3 from mutations in the alkyl-dihydroxyacetonephosphate synthase (ADAPS) gene [Wanders et al., 1994;de Vet et al., 1998].Until Wardinsky et al. [1990] reported five new cases and reviewed 21 literature cases, no one had attempted to delineate the natural history of RCP. Little has subsequently appeared concerning the clinical course in RCP. This study systematically addresses health concerns that arise in infants and children with RCP. Its intent is to present evidence-base...

The neurology of rhizomelic chondrodysplasia punctata

“…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].…”

Lipidomics Analysis of Peroxisomal Disorders: Discovery of Deficits in Phosphatidyglycerol Levels in Rhizomelic Chondrodysplasia Type 1

“…A key factor that negatively impacts the quality of lifestyle and ultimately limits longevity in RCDP1 patients is respiratory compromise with frequent lung infections and reactive airway disease [19,20]. In this regard, our observations of decreased phosphatidyglycerol levels in the plasma and lymphoblasts of RDDP1 patients is of significant notation.…”

Enfermedad peroxisomal, condrodisplasia rizomelica punctata tipo 1: reporte de caso

“…Some other abnormalities may occur in the eustachian tube, otitis media, and even hearing loss 10 . In addition, episodes of apnea and recurrent respiratory infections are common.…”

“…The parents are heterozygous carriers of the disease, thus the probability for each pregnancy of forming a child with the disease is of a 50%, with a 25% of having an affected children and a 25% of having a healthy child 10 . Molecular diagnosis is recommended, if available.…”

“…The mortality rate of this disease is focused on the first year of life 10 . The diagnosis is based on the clinical picture, also on laboratory tests given by biochemical tests such as determination of long fatty acids chains in plasma, plasmalogen levels, among others, and based on molecular diagnostic tests, if they are possible to perfom.…”