Peroxisomal Abnormality in Fibroblasts From Involved Skin of CHILD Syndrome

Abstract

The CHILD, C-H, and rhizomelic chondrodysplasia punctata syndromes are all characterized by ichthyosis, chondrodysplasia punctata, and limb defects, as well as peroxisomal deficiency. Thus, these syndromes may be related pathogenically. Because peroxisomes are involved in prostaglandin metabolism, peroxisomal deficiency may directly contribute to the previously reported alterations in prostaglandin metabolism in fibroblasts of involved skin of fibroblasts.

Peroxisomes in Dermatology. Part I

“…[11][12][13][14][15][16][17][18][19][20][21][22] Until recently peroxisomal disorders were listed under three main clinical syndromes: Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD). Polymalformations occur in classic ZS, as well as in rhizomelic (autosomal recessive) chondrodysplasia punctata (RCDP), X-linked dominant or recessive CDP [XCDP2 (Conradi-Hunermann-Happle syndrome], autosomal recessive CDP, and congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome.…”

“…Polymalformations occur in classic ZS, as well as in rhizomelic (autosomal recessive) chondrodysplasia punctata (RCDP), X-linked dominant or recessive CDP [XCDP2 (Conradi-Hunermann-Happle syndrome], autosomal recessive CDP, and congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome. [11][12][13][14][15][16][17][18][19] Neurologic manifestations predominate in NALD, and hepatodigestive manifestations in IRD. 11 However, with expansion in the understanding of the biochemical phenotypes within the spectrum of peroxisomal disorders, it has become obvious that there is little or no relationship between the clinical and biochemical phenotypes.…”

“…24 Twelve single peroxisomal enzyme disorders and a peroxisomal-microsomal disorder that appear secondary to a defect in a microsomal enzyme have also been identified, including a defect in 7-dehydrocholesterol-␦-7-reductase for Smith-LemliOpitz syndrome (SLOS), a defect in phytanoyl-coenzyme A hydroxylase (PAHX gene) for some cases of Refsum disease (RD), a defect in catalase for acatalasemia, a defect in the ATP-binding cassette transporter adrenoleukodystrophy protein for X-linked adrenoleukodystrophy, and a probable defect in microsomal 3␤-hydroysteroid-⌬8,⌬7-isomerase (⌬8,⌬7-sterol-isomerase) [patients with increased levels of 8-dehydrocholesterol and cholest-8(9)-en-3␤-ol] for some cases of XCDP2 and CHILD syndrome. 14,16,22,23 The phenotypic expression of the known PEX disorders and enzymatic defects appear to vary with the nature of the mutation. 22 In general, milder phenotypes are associated with mutations that do not abolish function completely or are associated with mosaicism.…”

Peroxisome Disorders and Cutaneous Manifestations

“…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.…”

“…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.…”