Abstract
Adult Refsum disease is an autosomal recessive peroxisomal disorder characterized by phytanic acid storage. Clinical symptoms usually begin in late childhood before the age of 20. Typical clinical presentation includes nyctalopia caused by retinitis pigmentosa, and anosmia. After 10–15 years, deafness, cerebellar ataxia, polyneuropathy, ichthyosis, and cardiac arrhythmia can occur.
We report the case of a very late-onset adult Refsum disease presenting with marked cognitive decline and severe leukoencephalopathy, without peripheral nervous system involvement. Brain MRI showed a leukoencephalopathy involving the periventricular white matter, subcortical area, and the brainstem with relative sparing of juxtacortical U fibers. This was associated with severe cortical and subcortical atrophy with ventricle dilatation. MR spectroscopy showed a marked increase in the choline/NAA ratio. Elevated plasma phytanic acid level was found, whereas plasma levels of pristanic and very long chain fatty acids were normal. The patient is homozygous for a previously undescribed PHYH frameshift mutation. Whether the very unusual phenotype is related to this peculiar mutation remains unclear.
Competing interests: None declared
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Communicated by: Ertan Mayatepek, MD
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A 69-year-old female patient, homozygous for a novel PHYH mutation, presented with an unusual Refsum disease phenotype including progressive dementia, gait apraxia, and memory loss, associated with diffuse leukoencephalopathy.
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Dr. Flavie Bompaire, Dr. Véronique Marcaud, Mrs. Emmanuelle Le Trionnaire, Dr. Frédéric Sedel, and Prof. Thierry Levade declare that they have no conflict of interest.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from the patient for being included in the study.
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This article does not contain any studies with animal subjects performed by any of the authors.
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Drs. Bompaire, Marcaud, and Sedel took care of the patient and diagnosed adult Refsum disease. Mrs. Le Trionnaire and Prof. Levade performed the genetic analysis and its interpretation. Dr. Bompaire wrote the text under the supervision of Dr. Sedel and Prof. Levade, with the help of Dr. Marcaud.
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Bompaire, F., Marcaud, V., Trionnaire, E.L., Sedel, F., Levade, T. (2014). Refsum Disease Presenting with a Late-Onset Leukodystrophy. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 19. JIMD Reports, vol 19. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_355
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DOI: https://doi.org/10.1007/8904_2014_355
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