Navigation Links
NIH scientists discover link among spectrum of childhood diseases
Date:10/31/2011

An international collaboration of scientists, including researchers at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the National Institutes of Health, has identified a genetic mutation that causes a rare childhood disease characterized predominantly by inflammation and fat loss. The research suggests that the disorder, named chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE), actually represents a spectrum of diseases that have been described in the literature under a variety of names. More importantly, since no effective treatment for this disease currently exists, the findings may have uncovered a possible target for future treatments.

The collaboration began when NIAMS rheumatologist Raphaela Goldbach-Mansky, M.D., started seeking the cause of inflammatory skin lesions, fat loss and fevers in two of her young patients. At a scientific meeting, she learned about recent publications by two other research groups one led by dermatologists Antonio Torrelo, M.D., from the Boy Jesus Hospital, Madrid, and Amy Paller, M.D., from Northwestern University, Chicago, and the other led by Abraham Zlotogorski, M.D., from the Hadassah-Hebrew University Medical Center, Jerusalem describing similar conditions. She immediately located the publications' authors and emailed them that same night.

"It turned out they had found each other and were looking for a genetic cause and additional cases," said Dr. Goldbach-Mansky. "I contacted them with a case report with pictures and they sent me theirs."

Based on the clinical presentation and, particularly, the unusual skin lesions seen in the children, the researchers suspected that the children must have the same disease. Subsequent analyses involving biopsies, blood tests and genetic testing confirmed their suspicions. All but one child had at least one mutation in a gene called PSMB8, which had been recently identified in three adult patients with a disease called joint contractures, muscle atrophy and panniculitis-associated lipodystrophy (JMP).

PSMB8 is one of more than 20 components involved in making a cellular structure called a proteasome, which recycles proteins from cells that are stressed or dying.

"When the proteasome doesn't function, there is a buildup of protein waste products in the cells much like if your trash wasn't picked up each week, it would accumulate in your driveway," said Dr. Goldbach-Mansky.

The one patient without the mutation had a blood profile that was identical to the ones who did, and showed the same accumulation of waste products in the cells seen in children with the genetic mutation. Blood tests also showed high levels of an inflammatory chemical called interferon gamma-induced protein 10 (IP-10) that is stimulated by interferons. The chemical is produced in response to some infections, and the group suspects that it also may be produced in the cellular stress response.

The discovery, which is described in Arthritis & Rheumatism, unifies several different diseases into one spectrum of proteasome-associated autoinflammatory syndromes, said Dr. Goldbach-Mansky. She hopes that these findings will enable doctors to identify more children who fit into this spectrum of difficult-to-treat disorders so that they can develop a better understanding of the disorders and their treatment.

Despite the best treatments currently available which, in most cases, consist of high doses of steroids children with these disorders continue to lose fat and suffer metabolic changes that lead to a range of problems, including loss of muscle mass, dilated heart muscles and cardiac arrhythmias. Treatments for other inflammatory diseases have little, if any, effect on the prognoses of these diseases. The group's findings, however, suggest new therapeutic targets.


'/>"/>

Contact: Trish Reynolds
reynoldsp2@mail.nih.gov
301-496-8190
NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases
Source:Eurekalert

Related medicine news :

1. Scientists Pinpoint Area of Brain That Fears Losing Money
2. Scientists Discover How HIV Is Transmitted Between Men
3. Prevention Is Key Research Goal for Premature Babies, Scientists Say
4. Scientists Discover Molecular Pathway for Organ Tissue Regeneration and Repair
5. Scientists find donut-shaped structure of enzyme involved in energy metabolism
6. Neuroscientists reveal new links that regulate brain electrical activity
7. Two UCSF Scientists to Receive Prestigious Dementia Research Honor
8. Johns Hopkins scientists develop personalized blood tests for cancer using whole genome sequencing
9. Scientists Spot Genetic Fingerprints of Individual Cancers
10. Scientists Unravel Mysteries of Intelligence
11. MSU scientists develop more effective method of predicting lead-poisoning risk
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/21/2017)... CA (PRWEB) , ... February 21, 2017 , ... Doctors ... , CA, directed by Dr. Kendell Mendonca , to its growing network of ... compensation injuries including injuries stemming from car accidents such as whiplash, back pain, neck ...
(Date:2/21/2017)... ... , ... Ray Insurance Agencies, a Dallas area firm providing asset protection services ... a six month charity event aimed at raising local support and donations that will ... the deadliest diseases in America; more than 7.5 million people die from cancer related ...
(Date:2/21/2017)... ... February 21, 2017 , ... ... the further expansion of its eHealth App xChange™, providing clinical researchers more ... Bioclinica’s extensive and growing eHealth platform. Applications that enable patient-centered clinical trials ...
(Date:2/21/2017)... ... February 21, 2017 , ... HIMSS is the ... care demonstration spanned multiple health information systems including OpenEMR, EMRDirect, and Epic. ... have no Health Information Exchange outside of faxing. Medal’s innovative technology “meets providers ...
(Date:2/21/2017)... (PRWEB) , ... February 21, 2017 , ... ... coffee house-caliber protein espresso drinks, announced its products are now available for purchase ... Coffee Protein Drink Mix has become popular among health-conscious consumers who love coffee ...
Breaking Medicine News(10 mins):
(Date:2/21/2017)... 2017 Sangamo Therapeutics, Inc. (Nasdaq: SGMO), the ... company will release its fourth quarter and full year ... February 28, 2017. The press release will be followed ... will be open to the public via telephone and ... its financial results and provide a business update. ...
(Date:2/21/2017)... , Feb. 21, 2017 ... announced a new imaging solution that connects Lexmark multifunction ... one of the world,s leading scanning and indexing software ... Connector enables hospitals to use a Lexmark MFP at ... the Solarity workflow, helping facilities reach HIMSS Stage ...
(Date:2/21/2017)... 2017 EMS Find, Inc. (OTCQB: EMSF), ... platforms with focus on e-commerce, health care and ... a worldwide, on-revocable and renewable Software Licensing and ... company serving healthcare organizations and facilities throughout ... EpicMD,s platform eliminates the need for health ...
Breaking Medicine Technology: