Featured Research

from universities, journals, and other organizations

Studies Of A Gene For A Rare Form Of Rickets Shed Light On Vitamin D Deficiencies

Date:
May 4, 1999
Source:
University Of California San Francisco
Summary:
Two years after they cloned the gene for a vital kidney enzyme, vitamin D-1-alpha hydroxylase, researchers at the University of California San Francisco are beginning to understand how the enzyme works. They are learning how it is regulated normally and how it acts abnormally in both a rare inherited form of rickets and in common forms of vitamin D deficiency, for example bone growth problems caused by chronic kidney failure or by aging.

Two years after they cloned the gene for a vital kidneyenzyme, vitamin D-1-alpha hydroxylase, researchers at theUniversity of California San Francisco are beginning tounderstand how the enzyme works. They are learning how it isregulated normally and how it acts abnormally in both a rareinherited form of rickets and in common forms of vitamin Ddeficiency, for example bone growth problems caused bychronic kidney failure or by aging.

Anthony Portale, MD, professor of pediatrics and chief ofpediatric nephrology at UCSF, presented these findings in aninvited symposium at the Pediatric Academic Societies'annual meeting in San Francisco on Sunday, May 2. Portaleand workers in the laboratory of pediatric endocrinologistWalter L. Miller, MD, collaborated in cloning the gene forthe enzyme in 1997.

The 1-alpha hydroxylase enzyme works in the kidney toperform one of the final steps in a long process thatconverts vitamin D -- the vitamin that comes in a morningglass of milk or is made when the skin is exposed tosunlight -- into a hormone called calcitrol. The main workfor calcitrol as a hormone is to regulate the absorption ofcalcium from the intestine into the blood and the depositionof calcium into bone. Without it, adult bones become brittleand children's bones do not grow. The calcitrol-calciumcombination also is necessary to aid nerve growth and musclefunction.

"Work with the gene has provided more evidence for what wealready suspected -- that production of the active form ofvitamin D hormone by the kidneys is essential for normalbone health and bone growth in children," Portale said. Thisis a particular concern for his patients; he leads thepediatric kidney dialysis and nephrology practice for LucilePackard Children's Hospital at UCSF. People with kidneyfailure do not have a genetic deficiency in vitamin Dmetabolism, but without normal kidney function they lose theability to make vitamin D in its active form.

Since cloning the 1-alpha hydroxylase gene, Portale and hiscolleagues have identified mutations in 19 patients.Children with these rare mutations cannot convert vitamin Dto calcitrol, and so suffer from rickets. "We now canidentify carriers of the gene in families," Portale said."We also can help make a diagnosis in a child who might have1-alpha hydroxylase deficiency, and clarify the prognosis.Once the genetic tests have been done, the physician candecide whether the child needs short-term nutritionaltherapy for rickets, or a lifetime of treatment withreplacement amounts of the active hormone."

Replacing the missing vitamin D hormone is a solution formost children, Portale said: "The rickets begin to heal, thebone deformities improve, the blood chemical values returnto normal. And the child begins to grow more normally."

Of the 19 people that Miller and Portale have studied with1-alpha hydroxylase rickets, 14 have different mutations ofthe gene controlling production of the vitamin D enzyme. Ina related disease, X-linked hypophosphatemic rickets, the1-alpha hydroxylase gene is normal but factors regulating itare abnormal; this problem is under active study by thePortale and Miller groups. Regulation of the enzyme also canbe abnormal in aging, and may contribute to osteoporosis.

"The long term goal of this work is to understand how thevitamin D enzyme is regulated, how it does its work, and howthese processes are abnormal in certain diseases," Portalesaid. "The most dramatic effects come with complete loss ofthe enzyme's function. But in other cases the function ispartial or abnormal, and that causes diseases that may needdifferent approaches to treatment."

Principal investigators Anthony Portale, MD, and Walter L.Miller, MD, are professors of pediatrics at the Universityof California, San Francisco. Much of the cloning work wasdone by Glenn K Fu, PhD, and the genetic analysis work byJonathan T. Wang, PhD, who are fellows in pediatricendocrinology at UCSF. This research is supported by grantsfrom the National Institutes of Health, the March of DimesBirth Defects Foundation, and the Carmel David Trust.

For a report on the 1997 cloning of vitamin D-1-alphahydroxylase, see http://www.ucsf.edu/daybreak/1997/11/1103_met.htr


Story Source:

The above story is based on materials provided by University Of California San Francisco. Note: Materials may be edited for content and length.


Cite This Page:

University Of California San Francisco. "Studies Of A Gene For A Rare Form Of Rickets Shed Light On Vitamin D Deficiencies." ScienceDaily. ScienceDaily, 4 May 1999. <www.sciencedaily.com/releases/1999/05/990504070029.htm>.
University Of California San Francisco. (1999, May 4). Studies Of A Gene For A Rare Form Of Rickets Shed Light On Vitamin D Deficiencies. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/1999/05/990504070029.htm
University Of California San Francisco. "Studies Of A Gene For A Rare Form Of Rickets Shed Light On Vitamin D Deficiencies." ScienceDaily. www.sciencedaily.com/releases/1999/05/990504070029.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Can Watching TV Make You Feel Like A Failure?

Can Watching TV Make You Feel Like A Failure?

Newsy (July 24, 2014) A study by German researchers claims watching TV while you're stressed out can make you feel guilty and like a failure. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile: iPhone Android Web
          Follow: Facebook Twitter Google+
          Subscribe: RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins