TY - JOUR
T1 - Sjögren-Larsson syndrome
T2 - Inherited defect in the fatty alcohol cycle
AU - Rizzo, William B.
AU - Dammann, Andrea L.
AU - Craft, Debra A.
AU - Black, Susan H.
AU - Tilton, Ann Henderson
AU - Africk, Diane
AU - Chaves-Carballo, Enrique
AU - Holmgren, Gösta
AU - Jagell, Sten
N1 - Funding Information:
Sj~gren-Larsson syndrome is an autosomal recessive disorder characterized by congenital ichthyosis, mental retardation, and spastic diplegia or tetraplegia. 1-3 Along with the typical triad of symptoms, many patients have glistening Supported by Basii O'Connor Starter Reserach Grant No. 5-476, March of Dimes; National Institutes of Health grant No. DK33914, and a grant from the Medical College of Virginia Children's Miracle Network Telethon. Submitted for publication Dec. 30, 1988; accepted March 3, 1989, Reprint requests: William 13. Rizzo, MD, Departments of Pediatrics and Human Genetics, Medical College of Virginia, PO Box 259, MCV Station, Richmond, VA 23298.
PY - 1989/8
Y1 - 1989/8
N2 - We investigated fatty alcohol metabolism in eight patients with Sjögren-Larsson syndrome, and in nine obligate heterozygotes. Fatty alcohol: nicotinamide-adenine dinucleotide oxidoreductase (FAO) activity was deficient in cultured skin fibroblasts (mean 18% of normal, n=8) and peripheral blood leukocytes (mean 22% of normal, n=3) from patients with Sjögren-Larsson syndrome. The palmitoyl coenzyme A-inhibitable component of FAO activity was decreased to 10% and 15% of normal in fibroblasts and leukocytes, respectively, of patients with Sjögren-Larsson syndrome. Most affected patients accumulated long-chain fatty alcohol in plasma, with a greater relative accumulation of octadecanol (mean threefold greater than normal) than hexadecanol (mean twofold greater than normal). Erythrocyte lipid alkyl ether linkages derived from hexadecanol were slightly increased in three of four patients. Fibroblasts and leukocytes from heterozygotes with Sjögren-Larsson syndrome showed mean FAO activities that were intermediate between those seen in homozygotes and in normal control subjects. The heterozygotes had normal fatty alcohol concentrations in plasma. These studies demonstrate FAO deficiency in patients with Sjögren-Larsson syndrome, and suggest that accumulation of fatty alcohol or its metabolic products may be important in the pathogenesis of this disorder.
AB - We investigated fatty alcohol metabolism in eight patients with Sjögren-Larsson syndrome, and in nine obligate heterozygotes. Fatty alcohol: nicotinamide-adenine dinucleotide oxidoreductase (FAO) activity was deficient in cultured skin fibroblasts (mean 18% of normal, n=8) and peripheral blood leukocytes (mean 22% of normal, n=3) from patients with Sjögren-Larsson syndrome. The palmitoyl coenzyme A-inhibitable component of FAO activity was decreased to 10% and 15% of normal in fibroblasts and leukocytes, respectively, of patients with Sjögren-Larsson syndrome. Most affected patients accumulated long-chain fatty alcohol in plasma, with a greater relative accumulation of octadecanol (mean threefold greater than normal) than hexadecanol (mean twofold greater than normal). Erythrocyte lipid alkyl ether linkages derived from hexadecanol were slightly increased in three of four patients. Fibroblasts and leukocytes from heterozygotes with Sjögren-Larsson syndrome showed mean FAO activities that were intermediate between those seen in homozygotes and in normal control subjects. The heterozygotes had normal fatty alcohol concentrations in plasma. These studies demonstrate FAO deficiency in patients with Sjögren-Larsson syndrome, and suggest that accumulation of fatty alcohol or its metabolic products may be important in the pathogenesis of this disorder.
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U2 - 10.1016/S0022-3476(89)80070-8
DO - 10.1016/S0022-3476(89)80070-8
M3 - Article
C2 - 2666627
AN - SCOPUS:0024475117
SN - 0022-3476
VL - 115
SP - 228
EP - 234
JO - The Journal of Pediatrics
JF - The Journal of Pediatrics
IS - 2
ER -