Elevated n-alkanes in congenital ichthyosiform erythroderma. Phenotypic differentiation of two types of autosomal recessive ichthyosis.

Abstract

Abstract. Previously considered to represent a single genetic disorder, autosomal recessive ichthyosis was examined in clinical and lipid biochemical studies of 18 patients with this condition and instead disclosed to be two distinct diseases. Six patients displayed clinical features of classical lamellar ichthyosis (LI), which is characterized by monomorphous features, including large, dark, platelike scales, severe ectropion, and a uniformly severe, unremitting course. 11 patients displayed clinical features of nonbullous congenital ichthyosiform erythroderma (CIE) characterized by fine white scales, prominent erythroderma, a milder course, and a variable prognosis. CIE could be separated biochemically from LI by the invariable presence ofelevated quantities of n-alkanes in scale (CIE, 24.8±1.9% vs. LI, 7.2+1.6%, and normal, 6.5±0.9%), which suggested a primary disorder in neutral lipid metabolism. In light ofthe distinctive clinical features of each, these biochemical studies indicate that autosomal recessive ichthyosis comprises two distinct disorders.

Sjögren-Larsson syndrome. Impaired fatty alcohol oxidation in cultured fibroblasts due to deficient fatty alcohol:nicotinamide adenine dinucleotide oxidoreductase activity.

“…Patients with ichthyosis due to neutral lipid storage disease accumulate triglyceride in skin and other tissues, including cultured fibroblasts (26,27). Some other inherited forms of ichthyosis have been associated with epidermal or scale lipid abnormalities (28,29), although no enzymatic defects have been identified; it (30) (Fig. 3).…”

Exogenous Origin of n-Alkanes in Pathologic Scale

“…Hence, it has been assumed generally that alkanes in skin lipids are environmental contaminants.47 In nor¬ mal human stratum corneum (SC), hydrocarbons can account for up to 5% to 10% of lipid,8 but lower quantities are found in both adult and neonatal murine SC.910 Al¬ though alkanes have been noted in large quantities (up to 40%) in some scale samples from patients with a va¬ riety of inherited disorders of cornification (DOC),11 alkane accumulation was a constant feature of one DOC, congenital ichthyosiform erythroderma (CIE), where they served as a marker to distinguish clinical sub¬ groups of autosomal recessive ichthyosis. 12,13 Because of their constant presence in normal SC and seemingly distinctive accumulation in some DOC, we have questioned whether these substances could be of endogenous origin.1113 Despite precau¬ tions to minimize environmental contamination prior to scale collection, elevated scale n-alkanes remained a constant feature in the initial group of patients with CIE.12,13 Moreover, the apparent inverse rela¬ tionship between the w-alkane and fatty acid/ triglycéride content of CIE scale suggested a possi¬ ble product/precursor relationship.11'13 However, attempts to demonstrate synthesis of alkanes from a variety of metabolic precursors have provided evi¬ dence for de novo synthesis in neural tissues,14,15 but not in epidermis.16…”

Autosomal dominant lamellar ichthyosis exhibits an abnormal scale lipid pattern

“…The concept that ARLI may be heterogeneous arose from clinical (Hazel1 & Marks 1985, Bernhardt & Baden 1986) and lipid biochemical studies. Williams & Elias (1984 found that some of their patients exhibited elevated scale n-alkanes and correlated these findings with clinical features of their patients with lamellar ichthyosis. They suggested that elevated scale nalkanes represent a biochemical factor which is capable of differentiating the erythrodermic (ELI) from the non-erythematous (NELI) variant of lamellar ichthyosis .…”

“…Several scaling skin disorders have been attributed to abnormalities of the intercellular lipid domains of the stratum corneum and it has been shown that several inherited scaling skin disorders could be differentiated by lipid biochemical analysis of scales (Williams & Elias 1986). Scales of autoso-ma1 recessive lamellar ichthyosis (ARLI) exhibit increased levels of free cholesterol (Williams 1983), whereas scale lipid analysis of patients with congenital ichthyosiform erythroderma (ELI) reveals increased amounts of n-alkanes (Williams & Elias 1984).…”