|Home- - -History-- -Bibliography- -Pregnancy Timeline- --Prescription Drugs in Pregnancy- -- Pregnancy Calculator- --Female Reproductive System- News Alerts -Contact|
Click weeks 0 - 40 and follow fetal growth
Identifying Brain Cells That Keep Us Awake
TBL1X Gene Involved In Autism Spectrum Disorder
“Love Hormone” Helps Direct Development of Brain
Steroids in Preemies Impair Brain Growth
Potential Treatment for Sickle Cell Disease
New Drug Shows Promise Against Multiple Sclerosis
Babies Understand Each Other at Ten Months Old
Bacteria Swap Genes Between Species Readily
Pinpointing Cause of Unexplained Miscarriage
Pregnant Mothers At Risk From Air Pollution
Linking A Spectrum of Childhood Diseases
Placenta and Uterus Battle Becomes Preeclampsia
Fetal Heart Rate Not a Good Indicator for Health
Swedish Discover Bisphenol-A Affects Newborn Brain
Not Your Mother's Birth Control
New research suggests that the disorder named chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE), is actually a spectrum of diseases that have been described in the literature under a variety of names.
More importantly, as no effective treatment for this disease exists, the findings may have uncovered a possible target for future treatments.
A collaboration began when National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) rheumatologist Raphaela Goldbach-Mansky, M.D., started looking for 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 still 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. It is produced in response to some infections, and the researchers suspect that it also may be produced in response to cellular stress.
The discovery, which is described in Arthritis & Rheumatism, unifies several different diseases into one - a spectrum of proteasome-associated autoinflammatory syndromes.
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 leading to loss of muscle mass, dilated heart muscles and cardiac arrhythmias. Treatments for other inflammatory diseases have little, if any, effect on its prognoses. The group’s findings, however, suggest new therapy targets.
Researchers are currently setting up a clinical protocol targeting the interferon pathway. Physicians and parents who suspect a child may fit the criteria for CANDLE should contact Dr. Goldbach-Mansky's research group (Nicole Plass: at 301-496-2237 or firstname.lastname@example.org).
The research was funded by the NIAMS Intramural Research Program and the Authority for Research and Development of the Hebrew University of Jerusalem. Additional support was provided by the National Human Genome Research Institute (NHGRI), the National Cancer Institute (NCI), and other institutions. The researchers plan to collaborate with researchers in other institutes within NIH, including the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the NHGRI. They hope to learn more about the role of the gene mutation in CANDLE that leads to the disease symptoms, and to search for the genetic cause in those children who have only one disease gene, or no disease-causing mutation, so far.
About the National Institutes of Health (NIH): NIH includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
Original article: http://www.nih.gov/news/health/oct2011/niams-31.htm