Redefining the Sjögren-Larsson syndrome: atypical findings in three siblings and implications regarding diagnosis.
BACKGROUND
The Sjögren-Larsson syndrome is a rare condition characterized by ichthyosis, spasticity, and mental retardation. Patients have deficient activity of the aldehyde portion of the fatty alcohol:nicotinamide adenine denucleotide (NAD+) oxidoreductase complex.


OBJECTIVE
Our purpose was to describe atypical findings in three siblings with the Sjögren-Larsson syndrome and implications regarding diagnosis.


METHODS
Medical histories were taken and physical examinations performed on four siblings and their parents. Analysis of fibroblast fatty alcohol:NAD+ oxidoreductase or fatty aldehyde dehydrogenase activity (or of both) was determined in each.


RESULTS
Decreased fibroblast fatty alcohol:NAD+ oxidoreductase or fatty aldehyde dehydrognase levels (or both) were present in three of four siblings. The fourth sibling and the parents had levels similar to obligate heterozygotes. None of the affected siblings fulfilled the classic criteria for the syndrome.


CONCLUSIONS
Although all affected siblings had abnormally low activity of the fatty alcohol:NAD+ dehydrogenase complex, their clinical findings were variable. This divergence of clinical features in siblings has not been previously reported. We propose that deficient activity of the fatty alcohol:NAD+ dehydrogenase complex be considered part of the definition of the Sjögren-Larsson syndrome that would also include the probable, but not absolute, presence of ichthyosis, mental retardation, and spasticity.
Medical College of Wisconsin, Milwaukee, USA.
J F
JF
Nigro
W B
WB
Rizzo
N B
NB
Esterly
D000293:Adolescent; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D002648:Child; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism; D016111:Sjogren-Larsson Syndrome / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics
D009097:Multienzyme Complexes; D000445:Aldehyde Oxidoreductases; C038828:long-chain-aldehyde dehydrogenase