LITTLE ROCK -- Does an elusive vitamin
deficiency cause cleft palates and shortened limbs in some babies?
A biochemist at the University of Arkansas for Medical Sciences (UAMS)
College of Medicine is leading the study of how biotin, a
micronutrient found in liver, egg yolk, milk, and yeast, may
affect fetal development. There appears to be a link between the
pregnant woman’s biotin intake and cleft palates, in which the
roof of the baby’s mouth is split. There also may be a link to
severely shortened arms and legs.
Dr. Donald M. Mock’s work is important enough that the National
Institutes of Health have given him a rare Merit Award – a
commitment to at least another decade of research funding at about
$225,000 per year. Mock has already received NIH funding for his
research for 18 consecutive years; the NIH Merit Award is a signal
that the federal agency expects him to continue making important
discoveries about the relationship of biotin, a member of the B
complex group of vitamins to birth defects. Mock’s Merit Award
is the first at UAMS.
The American Journal of Clinical Nutrition praised Mock and
his colleagues in 2002 for their persistent research. The group at
UAMS (along with Dr. J. Gerald Quirk, an obstetrician formerly at
UAMS and now at State University of New York) has established a
reliable urine test for mild, or marginal, biotin deficiency – a
critical step in the painstaking process of confirming and
explaining why biotin deficiency causes birth defects.
Mock has been studying biotin since 1979, when he stumbled upon
the diagnosis for an eight-month-old girl’s heartbreaking
ailments, including an abnormally short intestine, hair loss, skin
rash, and extreme lethargy. At the time, Mock was a fellow in
pediatric gastroenterology at the University of California-San
Francisco.
"I walked into the pediatric treatment room at Moffitt
Hospital and saw these surgeons doing a dressing change on an
eight-month-old girl. She had an abnormally short intestine, rash,
hair loss, and was very inactive despite the IV nutrition. I
asked, ‘When are you going to properly diagnose that
zinc-deficient kid?’ The surgery team treated her for zinc
deficiency but she didn’t get better, so they came back, asking
‘What else could this be?’ I knew of 1940s studies of biotin
deficiency and I’d seen inborn errors of metabolism that related
to biotin, but no one had diagnosed biotin deficiency in an IV-fed
patient." Nonetheless, Mock speculated that the baby suffered
from biotin deficiency. He gave her biotin supplements and she
improved dramatically.
The New England Journal of Medicine published a report of
the case. Now biotin is a standard part of intravenous feedings
and such cases no longer occur. This clinical observation launched
Mock’s studies of biotin; he is recognized as one of the world’s
leading researchers in the field.
Now a professor of biochemistry, molecular biology and pediatrics
in the UAMS College of Medicine, Mock has confirmed and extended
research findings in Japan that mild biotin deficiency causes
defects in the roof of the mouth and shortened limbs in animals.
The defects seem to occur early in pregnancy in animals with
biotin deficiency.
Mock also has determined that mild biotin deficiency occurs in at
least one third of normal human pregnancies. He and his research
team have perfected a laboratory test for biotin deficiency that
eventually may help obstetricians identify women who need extra
biotin during pregnancy. Thanks to volunteers in related studies,
Mock and his research group have developed the technique for
detecting biotin at the tiny level of two parts per trillion.
Volunteers live in the UAMS General Clinical Research Center for
four weeks, eating a low-biotin diet and providing regular blood
and urine samples.
Mock stresses that the researchers
at UAMS only induce mild biotin deficiency in volunteers in
order to devise a reliable laboratory test for the deficiency. The
deficiency they induce in the volunteers is too mild to cause
symptoms. The researchers also exclude pregnant women from the
project in order to protect their fetuses.
Many unanswered questions about
biotin remain, however. The link between biotin deficiency and
birth defects in animal subjects does not prove a link in humans,
so Mock is collecting blood samples from newborn babies with
defects at UAMS to determine their biotin status at birth.
If the link can be proven in
humans, scientists will also need to determine exactly how severe
the deficiency must be to cause defects, and why it occurs in some
women and not in others. Is there a genetic basis for severe
biotin deficiency in pregnancy? If so, can women with the genetic
predisposition be identified through a simple genetic test – and
can they receive safe levels of supplemental biotin during
pregnancy?
Meanwhile, Mock does not recommend
that pregnant women take biotin supplements on their own, because
neither the link between biotin deficiency and certain birth
defects, nor a safe level of biotin supplement, are clear yet.
In some ways, Mock’s research
descends from studies of folate therapy in pregnancy, which
prevents neural tube defects. After scientists established the
link between folate supplementation and prevention of neural tube
defects in the 1990s, the federal government ordered manufacturers
of bread and other foods with enriched flour to add folic acid to
their products. Scientists, including a group at UAMS and the
National Center for Toxicological Research at Jefferson, Ark.,
continue to analyze the role of folic acid in fetal development.
One avenue of research involves pregnant women who have babies
with neural tube defects despite appearing to consume enough
folate. One possible explanation is that those women belong to a
genetic subgroup that needs more than the normal amount of folic
acid to have healthy babies.
Donald M. Mock, Ph.D. (UAMS) Click
on image for print-quality resolution.
|
Donald M. Mock, Ph.D., and research associate Nell Mock (UAMS) Click
on image for print-quality resolution. |
This baby developed severe biotin
deficiency during intravenous feeding without biotin. (UAMS) Click
on image for print-quality resolution. |
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