Adult Chediak-Higashi Parkinsonian syndrome with dystonia

Hauser, Robert A.; Friedlander, Jeffrey; Baker, Matthew J.; Thomas, Jeffrey; Zuckerman, Kenneth S.

doi:10.1002/1531-8257(200007)15:4<705::aid-mds1016>3.0.co;2-b

Cited by 25 publications

(25 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…10,11 Various neurologic symptoms have been described in CHS, mostly in young adults. 8,[12][13][14][15][16] However, no large series of patients with CHS with neurologic expression has been reported because only 10% of patients have a milder form of the disease and survive childhood without BMT. It is unclear whether neurologic manifestations result directly from defective function of lysosome trafficking regulator protein (LYST) in neurons and glial cells, from lymphocyte infiltration into the central nervous system (CNS) in the accelerated phase of the disease, or both.…”

Section: Introductionmentioning

confidence: 99%

Progressive neurologic dysfunctions 20 years after allogeneic bone marrow transplantation for Chediak-Higashi syndrome

Tardieu

Lacroix

Neven

et al. 2005

Blood

114

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Progressive neurologic dysfunctions 20 years after allogeneic bone marrow transplantation for Chediak-Higashi syndrome

Tardieu

Lacroix

Neven

et al. 2005

Blood

114

View full text Add to dashboard Cite

“…Oxidative membrane damage resulting from aberrant LYST function could have particularly important ramifications for the neurodegenerative component of Chediak-Higashi syndrome [1], [27]. Elevated levels of oxidized lipids have been observed in several neurodegenerative diseases [28].…”

Section: Resultsmentioning

confidence: 99%

Elevated Oxidative Membrane Damage Associated with Genetic Modifiers of Lyst-Mutant Phenotypes

et al. 2010

View full text Add to dashboard Cite

LYST is a large cytosolic protein that influences the biogenesis of lysosome-related organelles, and mutation of the encoding gene, LYST, can cause Chediak-Higashi syndrome. Recently, Lyst-mutant mice were recognized to also exhibit an iris disease resembling exfoliation syndrome, a common cause of glaucoma in humans. Here, Lyst-mutant iris phenotypes were used in a search for genes that influence Lyst pathways. In a candidate gene–driven approach, albino Lyst-mutant mice homozygous for a mutation in Tyr, whose product is key to melanin synthesis within melanosomes, exhibited complete rescue of Lyst-mutant iris phenotypes. In a genetic background–driven approach using a DBA/2J strain of congenic mice, an interval containing Tyrp1 enhanced Lyst-dependent iris phenotypes. Thus, both experimental approaches implicated the melanosome, an organelle that is a potential source of oxidative stress, as contributing to the disease phenotype. Confirming an association with oxidative damage, Lyst mutation resulted in genetic context–sensitive changes in iris lipid hydroperoxide levels, being lowest in albino and highest in DBA/2J mice. Surprisingly, the DBA/2J genetic background also exposed a late-onset neurodegenerative phenotype involving cerebellar Purkinje-cell degeneration. These results identify an association between oxidative damage to lipid membranes and the severity of Lyst-mutant phenotypes, revealing a new mechanism that contributes to pathophysiology involving LYST.

show abstract

“…Neuere Beschreibungen eines Parkinson-Syndroms im Rahmen des CHS weisen auf eine L-Dopa-Responsivität hin [12,14,22,26], passend zu einer reduzierten Dopamintransporter-Liganden-Bindung im FP-CIT-SPECT bei einem Patienten [14]. Histologisch konnten Sung et al [27] übergroße, irregulär verklumpte melaninhaltige Granula in Zellen der Substantia nigra eines CHS-Patienten nachweisen.…”

Section: Chs Und Nervensystemunclassified

“…Weitere neurologische Komplikationen umfassen eine Schädigung der PyraAbb 1 9 Blutausstrich mit eosinophilen, peroxidasepositiven Riesengranula in neutrophilen Granulozyten bei einem 22-jährigen Patienten mit Chediak-Higashi-Syndrom midenbahn [24], dystone Störungen [12], eine demenzielle Entwicklung [29], epileptische Anfälle [3,19] und Hirnnervenausfälle, überwiegend in Form einer Fazialisparese [3]. Ferner wurde eine retinale Pigmentdegeneration mit zunehmender Einschränkung des Gesichtsfeldes beschrieben [23].…”

Section: Chs Und Nervensystemunclassified

See 1 more Smart Citation

Das Chediak-Higashi-Syndrom

et al. 2006

View full text Add to dashboard Cite

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive lysosomal disorder characterized by frequent infections, oculocutaneous albinism, high bleeding tendency, and various neurological symptoms. Onset in early childhood mostly leads to lymphohistiocytic infiltration into multiple organs, which is usually lethal without bone marrow transplantation. The adult form of CHS has a milder course, no lymphohistiocytic infiltration, and is characterized by neurological manifestations such as polyneuropathy, parkinsonism, dementia, and ataxia. In young adults, a combination of these defects with oculocutaneous albinism or recurrent infections should bring CHS into consideration. Diagnosis is established by the presence of characteristic eosinophilic peroxidase-positive giant granules in leukocytes. This article summarizes current knowledge about the pathogenesis, clinical course, and therapy of CHS and reports on experience with two adult CHS patients.

show abstract

Adult Chediak-Higashi Parkinsonian syndrome with dystonia

Cited by 25 publications

References 9 publications

Progressive neurologic dysfunctions 20 years after allogeneic bone marrow transplantation for Chediak-Higashi syndrome

Progressive neurologic dysfunctions 20 years after allogeneic bone marrow transplantation for Chediak-Higashi syndrome

Elevated Oxidative Membrane Damage Associated with Genetic Modifiers of Lyst-Mutant Phenotypes

Das Chediak-Higashi-Syndrom

Contact Info

Product

Resources

About