Oxidative stress & Wilson disease

• May 17th, 2012

A recent study by Bruha et al. suggests that increased oxidative stress may contribute significantly to the clinical manifestation of Wilson disease, an inherited disorder of copper disposition caused by an ATP7B transporter gene mutations.

Decreased serum antioxidant capacity in patients with Wilson disease is associated with neurological symptoms. Bruha et al. J Inherit Metab Dis. 2012 May;35(3):541-8. Epub 2011 Dec 3. PMID: 22139496

posted by Yannis Trakadis MD, MSc

Disorders of selenium metabolism

• June 16th, 2011

A review of  disorders of selenium metabolism and selenoproteins was recently publised in Current Opinion in Pediatrics. It includes up to date descriptions of SECISBP2 syndrome, causing thyroid dysfunction and growth retardation, and SEPSECS mutations causing progressive cerebellar and cerebral atrophy. Other abnormalities seen in impaired selenium metabolism include impaired muscle function, and immune deficits.

(Schweizer et al, Current Opinion in Pediatrics, 2011, 23:June 8, epub.)

Posted by Hilary Vernon MD PhD

Treatment of Wilson disease with NaPB

• January 5th, 2010

Chaperones such as phenylbutyrate and curcumin can be used to treat conditions with misfolded proteins such as ATP7 in Wilson Disease.

Hepatology. 2009 Dec;50(6):1783-95.
Reduced expression of ATP7B affected by Wilson disease-causing mutations is rescued by pharmacological folding chaperones 4-phenylbutyrate and curcumin.
van den Berghe PV, Stapelbroek JM, Krieger E, de Bie P, van de Graaf SF, de Groot RE, van Beurden E, Spijker E, Houwen RH, Berger R, Klomp LW.

Phenylbutyrate also has other pharmacological effects, such as HDAC inhibition,  ↓ stability of HSC70 mRNA leading to ↓ degradation of ΔF508 CFTR, ↑ PPARG activation, isoprenylation inhibition, and ↓ methylation. These properties render it an attractive compound for the treatment of other genetic conditions such as cystic fibrosis and thalassemias.

Philippe Campeau

Epilepsy in Menkes disease

• May 24th, 2006

Epilepsy in Menkes disease: analysis of clinical stages.
Epilepsia. 2006 Feb;47(2):380-6.
Bahi-Buisson N et al.
12 patients with Menkes disease are studied. Their epilepsy is characterized by three successive periods:
early focal status
infantile spasms
myoclonic and multifocal epilepsy

For more information on Menkes disease, please see chapter 126

Thank you very much in advance for your contributions to this blog.
Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator