Dermatologic Manifestations of Sjogren-Larsson Syndrome Workup

Updated: Apr 16, 2021
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD  more...
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Workup

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. [30]  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. [31] 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. [32, 33, 34]

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). [35]

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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. [36]

Next-generation sequencing may be used for diagnosis. [37]

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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). [38]

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