Rhizomelic chondrodysplasia punctata with isolated DHAP-AT deficiency.

Abstract

An infant with the characteristic

Defective lipid remodeling of GPI anchors in peroxisomal disorders, Zellweger syndrome, and rhizomelic chondrodysplasia punctata

“…Patients with RCDP types 2 and 3 have craniofacial dysmorphism, cataract, severe psychomotor retardation, as well as rhizomelia and chondrodysplasia punctata ( 3,(10)(11)(12). It is tempting to speculate that the lack of a particular 1-alkyl-2-acyl GPI-AP is responsible for some of these abnormalities.…”

“…RCDP type 1 is caused by mutation in PEX7 that is essential for transferring the minor group of enzymes bearing a PTS2, such as 3-ketoacyl-CoA thiolase of fatty-acid ␤ -oxidation pathway, alkyl-dihydroxyacetone phosphate synthase (alkyl-DHAP synthase), which is required for synthesis of alkyl-phospholipids, and phytanoyl-CoA 2-hydroxylase, which is required for degradation of phytanic acid ( 3 ). Specifi c defects in DHAPacyltransferase (DHAP-AT) and alkyl-DHAP synthase (also called alkylglycerone phosphate synthase), the fi rst two enzymes in the alkyl-phospholipid biosynthetic pathway, cause disorders similar to RCDP type 1, termed RCDP type 2 and type 3, respectively (10)(11)(12), indicating that the major symptoms of RCDP are due to defective biosynthesis of plasmalogens and/or other alkyl-phospholipids, such as platelet activating factor.…”

Abnormal myelin formation in rhizomelic chondrodysplasia punctata type 2 (DHAPAT‐deficiency)

“…Individuals with all the clinical signs and symptoms of RCDP but with an isolated single deficiency of either DHAPAT (RCDP type 2) or alkyl-DHAP synthase (RCDP type 3) have been identified (Wanders et al 1992, Wanders et al 1994, Ofman et al 1998. Clinical heterogeneity has also been observed, even among individuals with isolated DHAPAT deficiency: cases of a milder, variant form of chondrodysplasia punctata have been described in addition to those with the classic clinical manifestations (Wanders et al 1992, Barr et al 1993, Clayton et al 1994, Hebestreit et al 1996.…”

Peroxisome Disorders and Cutaneous Manifestations

“…Refsum's disease [8], as well as rhizomelic chondrodysplasia punctata [5] and CHILD syndrome [6] are associated with skin alterations, an ichthyotic-likc condition [9], In this issue of Dermatology, Papini et al [8] report the dermatological findings in a patient with X-linked ALD and the metabolic disturbances detectable in the skin sur face lipids.…”

“…Peroxisomes arc present in almost all mammalian cells (except erythrocytes) including keratinocytes [2], Several inborn defects of peroxisomal function have been identified: Zellweger syndrome [3], adrcnoleukodystrophy (ALD) [4], rhizomelic chondrodysplasia punctata [5], CHILD syndrome [6], hyperpiperolic acidemia and infantile Rcfsum's disease [7], Of these. Refsum's disease [8], as well as rhizomelic chondrodysplasia punctata [5] and CHILD syndrome [6] are associated with skin alterations, an ichthyotic-likc condition [9], In this issue of Dermatology, Papini et al [8] report the dermatological findings in a patient with X-linked ALD and the metabolic disturbances detectable in the skin sur face lipids.…”