Clinical trial NCT01971957: Sjogren-Larsson Syndrome: Natural History, Clinical Variation and Evaluation of Biochemical Markers
Official title: Sjogren-Larsson Syndrome: A Longitudinal Study of Natural History, Clinical Variation and Evaluation of Biochemical Markers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sjogren-Larsson Syndrome (SLS)
Keywords: ichthyosis
spasticity
spastic diplegia
intellectual disability
Lead sponsor: University of Nebraska
Sponsor class: OTHER
First posted: 2013-10-30
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will come from cohorts of Sjögren-Larsson syndrome patients currently followed at STAIR sites, from the RDCRN contact registry, and from the pool of new patients who directly contact STAIR sites or are referred to STAIR centers by their physicians.

Brief summary: Sjogren-Larsson syndrome (SLS) is a rare genetic disease in which patients typically exhibit ichthyosis (dry, scaly skin), intellectual disability, spasticity, seizures and a distinctive maculopathy. The purpose of this study is to define the clinical spectrum and natural history of Sjogren-Larsson syndrome, and identify biomarkers that correlate with disease phenotype while establishing a registry for future investigations of biochemical pathogenesis and therapy.

Detailed description: The study will consist of a clinical component and a scientific component consisting of laboratory investigations of potentially useful biochemical (lipid and protein) markers. Up to 50 SLS patients of all ages, gender and ethnic origins will be enrolled. A detailed clinical evaluation will be performed to determine the presence and extent of disease involving the skin, nervous system and eyes. Clinical testing will include brain magnetic resonance imaging (MRI) and spectroscopy (MRS), electroencephalography (EEG), neurocognitive tests, ophthalmologic examination with retinal photographs and optical coherence tomography (OCT), photographs of the skin and tests of cutaneous transepidermal water loss. Laboratory investigations will include lipid analyses (e.g. fatty alcohols, farnesol, fatty acids, ether glycerolipids, etc.) of blood, skin and urine; proteomic analysis of skin (stratum corneum); and measurements of leukocyte fatty alcohol and farnesol oxidation. A skin biopsy (optional) will be obtained for electron microscopy, measurement of lanthanum perfusion (transepidermal water loss), and/or establishing keratinocyte cultures. Correlations between clinical abnormalities and laboratory measurements will be tested to identify the most useful biomarkers for future diagnostic and therapeutic studies. To characterize the progression of phenotypic features over time, patients \<6 years of age will be followed yearly and patients ≥6 years of age will be followed every 3 years. In addition, a SLS patient registry will be established as a resource for future investigations in SLS.

Eligibility criteria: Inclusion Criteria:

* The only eligibility criterion is that subjects have a genetically or biochemically confirmed diagnosis of Sjogren-Larsson syndrome.

Exclusion Criteria:

* The primary exclusion criteria are the patients' failure to consent or inability to travel to a STAIR site.

Primary outcomes:
measure: Characterize the extent and progression of neurocutaneous disease in patients with Sjogren-Larsson syndrome (SLS).
timeFrame: 2017 (up to 5 years)
Secondary outcomes:
measure: Identify biomarkers that correlate with disease severity.
timeFrame: 2017 (up to 5 years)
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Nebraska
name: William B Rizzo, MD
role: STUDY_CHAIR
References:
citation: Rizzo WB. Sjogren-Larsson syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Mol Genet Metab. 2007 Jan;90(1):1-9. doi: 10.1016/j.ymgme.2006.08.006. Epub 2006 Sep 22.
citation: Lossos A, Khoury M, Rizzo WB, Gomori JM, Banin E, Zlotogorski A, Jaber S, Abramsky O, Argov Z, Rosenmann H. Phenotypic variability among adult siblings with Sjogren-Larsson syndrome. Arch Neurol. 2006 Feb;63(2):278-80. doi: 10.1001/archneur.63.2.278.
citation: Rizzo WB, Craft DA, Somer T, Carney G, Trafrova J, Simon M. Abnormal fatty alcohol metabolism in cultured keratinocytes from patients with Sjogren-Larsson syndrome. J Lipid Res. 2008 Feb;49(2):410-9. doi: 10.1194/jlr.M700469-JLR200. Epub 2007 Oct 30.
citation: Fuijkschot J, Theelen T, Seyger MM, van der Graaf M, de Groot IJ, Wevers RA, Wanders RJ, Waterham HR, Willemsen MA. Sjogren-Larsson syndrome in clinical practice. J Inherit Metab Dis. 2012 Nov;35(6):955-62. doi: 10.1007/s10545-012-9518-6. Epub 2012 Jul 26.
citation: Rizzo WB. The role of fatty aldehyde dehydrogenase in epidermal structure and function. Dermatoendocrinol. 2011 Apr;3(2):91-9. doi: 10.4161/derm.3.2.14619. Epub 2011 Apr 1.
citation: Rizzo WB, Carney G. Sjogren-Larsson syndrome: diversity of mutations and polymorphisms in the fatty aldehyde dehydrogenase gene (ALDH3A2). Hum Mutat. 2005 Jul;26(1):1-10. doi: 10.1002/humu.20181.
citation: Willemsen MA, Van Der Graaf M, Van Der Knaap MS, Heerschap A, Van Domburg PH, Gabreels FJ, Rotteveel JJ. MR imaging and proton MR spectroscopic studies in Sjogren-Larsson syndrome: characterization of the leukoencephalopathy. AJNR Am J Neuroradiol. 2004 Apr;25(4):649-57.