Dermatologic Manifestations of Sjogren-Larsson Syndrome Workup

  • Author: Anna Zalewska, MD, PhD; Chief Editor: William D James, MD   more...
 
Updated: Aug 17, 2011
 

Laboratory Studies

  • Sjögren-Larsson syndrome (SLS) is diagnosed by demonstrating the enzyme deficiency or by mutation analysis of the FALDH gene. To date, more than 70 different FALDH gene mutations have been found in patients with Sjögren-Larsson syndrome.
  • FALDH or FAO activity is measured in cultured skin fibroblasts or leukocytes.
    • Median FALDH activity in healthy control subjects is estimated to be 8540 ±1158 pmol/min/mg of protein
    • Normal control values of FAO activity are estimated to be 75 ±13 pmol/min/mg of protein.
    • Patients who are affected usually have less than 10% of the normal mean FALDH activity in cultured skin fibroblasts, and obligate Sjögren-Larsson syndrome heterozygotes demonstrate reduced enzyme activity to about 50% of the normal value.
    • FALDH activity is also deficient in cultured keratinocytes, peripheral blood leukocytes, and other tissues of patients who are affected.
  • An accumulation of fatty alcohols (hexadecanol and octadecanol) occurs in plasma.
  • In contrast, free fatty aldehyde levels are not elevated.
  • Routine laboratory investigations of plasma, urine, and cerebrospinal fluid do not reveal any consistent diagnostic abnormalities.
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Imaging Studies

  • Cranial CT findings are consistent with cortical atrophy (white brain hypodensity that varies from frontal patches to diffuse confluent involvement). The severity of the CT findings is correlated well with the severity of the neurologic symptoms.
  • Brain MRI demonstrates white matter disease characterized by dysmyelination or delayed myelination.[20]
    • Dysmyelination is defined as a breakdown of already formed (also delayed) myelin.
    • Delayed myelination is a delay of myelin deposition, demonstrable by follow-up MRI examinations.[21] In such cases, normal myelin is demonstrable at a later point in development at sites where no mature myelin signal was noticed on earlier MRI. Without follow-up data, the term hypomyelination might be applied in such cases.
  • Protein magnetic resonance (MR) spectroscopy findings include abnormal pick at 1.3 ppm, consistent with long-chain fatty alcohol accumulation, in the periventricular white matter (mostly around the posterior and frontal horns.[22, 23, 24]
  • Optical coherence tomography (OCT) demonstrates morphologic changes in the macula (ie, crystalline macular dystrophy with cystoid foveal atrophy, focal hyperreflectivities within the perifoveal ganglion cell layer and the inner plexiform layer).[25]
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Other Tests

  • Analysis of LTB4 and its metabolites in urine offers a new and noninvasive diagnostic examination for patients with Sjögren-Larsson syndrome.
  • Electroencephalography (EEG) demonstrates multifocal epileptic discharges (eg, spike and wave complexes, polyspikes, sharp waves of high voltage) occurring in the presence of disorganized background activity.
  • Electrospray ionization mass spectrometry (ESI-MS) used to quantify the amounts of the dicarboxylic acid of C22:0 (C22:0 -DCA) allows for reliable and rapid diagnosis of Sjögren-Larsson syndrome.[26]
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Histologic Findings

Skin biopsy samples demonstrate hyperkeratosis, focal parakeratosis, acanthosis, papillomatosis, and a sparse dermal lymphocytic inflammatory infiltrate. Ultrastructural examination reveals abnormal lamellar inclusions in the cytoplasm of spinous, granular, and horny cells; prominent Golgi apparatus; and an increased number of mitochondria. Sometimes, lipid droplets are seen in the horny layer. Postmortem brain histopathologic examination reveals a basic disorder of central myelination, usually a mild loss of gray matter, including basal ganglia, with a tendency toward accumulation of astrocytes and lipoid substances (eg, lipids, lipofuscinlike pigments).[27]

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Contributor Information and Disclosures
Author

Anna Zalewska, MD, PhD  Professor of Dermatology and Venereology, Psychodermatology Department, Chair of Clinical Immunology and Microbiology, Medical University of Lodz, Poland

Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

Jacek C Szepietowski, MD, PhD  Professor, Vice-Head, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University; Director of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland

Disclosure: Stiefel GSK Company Salary Employment; Orfagen Consulting fee Consulting; Maruho Consulting fee Consulting; Astellas Consulting fee Consulting; Abbott Consulting fee Consulting; Leo Pharma Consulting fee Consulting

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD  Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and American College of Rheumatology

Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Electrical Optical Sciences Consulting fee Consulting; Celgene Honoraria Safety Monitoring Committee; GSK - Glaxo Smith Kline Consulting fee Consulting; TenXBioPharma Consulting fee Safety Monitoring Committee

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD  Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System

William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: Elsevier Royalty Other

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