M S U D Newsletter
Articles selected from
Vol. 10, No. 2, Dec. 1992
This
issue includes a brief review in words and pictures of Symposium â92.Ê Dr. Elsas shares some exciting news on his
latest research project and Dr. Morton describes the medical implications of
brain surgery on a young boy with MSUD.
SUMMARY
OF SYMPOSIUM 1992÷TORONTO
This was our 6th biennial
family-sponsored Symposium.Ê Forty-five
families attended, many bringing their children with MSUD and their siblings
for a total of fifty-five children.Ê
Other family members and professionals brought the total to 189.Ê The Symposium was well organized.Ê The atmosphere was comfortable and the food
ample.Ê The baby-sitting service kept
the children supervised and entertained.Ê
Comments were positive.
The Agenda
Friday a.m.- June 5
Welcome & Update on
Ontario Association for MSUD Research from the Toth and Sullivan families
The host families
extended a warm welcome.Ê They explained
the association they established to help fund the Symposium and MSUD
research.Ê Each person had been given a
green cap with the Ontario Association logo during registration and were
encouraged to wear them.Ê Mike Sullivan
faithfully wore his cap while moderating the conference in a lively manner.
Opening Comments and Thoughts
on MSUD: The Disease
by Dr. Roderick McInnes, M.D., Ph.D., F.R.C.P.Ê
Associate Professor of Pediatrics and Medical Genetics, Hospital for
Sick Children, Toronto, ON
Dr. McInnes, in
discussing genetics, told us everyone carries 8 to 10 genes that could cause
severe diseases.ÊÊ He described the
treatment and home management of MSUD.Ê
There are many variations of MSUD in patients, Dr. McInnes explained,
and severalÊ unknown factors, such as
which blood levels of BCAA are safe and what factors cause brain
intoxication.Ê He summed up three things
he learned from his experience with MSUD÷listen to the parents, small details
are critical (like weighing food), and advances will be in small steps (with
the possible exception of gene therapy).Ê
Our goals should be to develop our group, support genetic research, stay
sophisticated÷donât go for the quick fixes, and make your physician
listen.Ê
Two-Year Correlation
Study of 2,4-DNPH, Keto-stix, and Blood Amino Acid Levels by Doreen Anderson,
Nurse Coordinator, Hospital for Sick Children, Toronto, and Alice T. Mazur,
R.N., P.N.P., Division of Metabolism,Ê
Childrenâs Hospital of Philadelphia, PA
Alice Mazur stated that
intellectual outcome for persons with MSUD depends on the age of diagnosis and
levels of chronic control.Ê A pilot
program for newborn screening in PA began in several counties in the spring of
1991 and is to be extended statewide later.Ê
Chronic control involves a monthly analysis of leucine blood levels plus
a dietary leucine analysis and early intervention in illness using DNPH urine
testing.Ê Doreen Anderson gave data on
39 DNPH urine testings. There were puzzling variations in the test
results.Ê The small sampling made it
hard to draw any conclusions.
Teen Perspective on MSUD by Elio Cannella
Elio, a teenager with
MSUD from Ontario, told his story.Ê He
was born March 12, 1974 and diagnosed at 13 days of age.Ê He spent 2 weeks in intensive care and 3
months in the hospital.Ê He has cerebral
palsy and did not walk until he was 3 yrs. old.Ê He planned to enter thirteenth grade this fall, studying computer
graphics.Ê He plays piano, likes
wrestling, and has twin brothers who protect him.Ê It does not bother him to have MSUD; he has accepted it and
learned to cope with it.Ê His friends
accept him as he is.Ê He always follows
his diet, counting equivalents, but is angry at the formula.Ê Watching other people eat doesnât bother
him.Ê Since he has not tasted many of
the foods, he doesnât miss them.Ê At
eighteen he is doing quite well.
Reflection of MSUD with
Case Histories
by Dr. John Menkes, M.D., Professor Emeritus of Neurology and Pediatrics,
University of California School of Medicine
It all started in Boston
in 1952.Ê Doctors had just learned about
the effects of a restrictive diet in preventing retardation in PKU.Ê Dr. Menkes had just finished medical school
when he became interested in a mother who had the 4th baby with a peculiar
smell in the urine.Ê The other three had
died and at 14 days of age, this one did too.Ê
Dr. Menkes described his long, arduous task of trying to learn the cause
of the odor.Ê It was a fascinating story
of determination and perseverance.Ê The
first child with MSUD was treated in 1957 by Selma Snyderman.Ê Dr. Menkes concluded by mentioning there are
twelve different forms of MSUD known to date, and there is a possibility of
gene replacement within 5 to 10 years.
Low Protein Products by
Specialty Food Shops and Kingsmill Foods, Ltd.
This was a description
of two non-profit food shops in the Toronto area.Ê Kingsmill special food items were introduced and displayed.Ê Samples of a number of low protein foods
were available.
MSUD: Current and Future
Prediction and Therapy by Louis J. Elsas II, M.D., Professor of Pediatrics,
Director of the Division of Medical Genetics, Emory University School of
Medicine, Atlanta, GA
Dr. Elsas stressed the
importance of early intervention in MSUD involving four components: screening,
retrieval, diagnosis and treatment.Ê
Screening began in 1978 in Georgia.Ê
Eleven cases were found by Dec. 1991÷37% are African American.Ê He explained his special research project
which would involve some of the children at the Symposium.Ê (See Field Trial at Symposium.)
Maternal Dietary Issues
in MSUDÊ by Sandy Van Calcar, R.D., Metabolic
Nutritionist, Weisman Center, University of Wisconsin
Sandy gave an account of
Sue Ann McKnightâs medical care during her pregnancy.Ê Although Sue Ann is considered to have classic MSUD, she
ordinarily tolerates more protein than most other classics.Ê She was the first woman with MSUD to give
birth to a child.Ê She delivered a
normal, healthy baby after a very closely monitored pregnancy.Ê Her protein and carnitine needs were much
greater during pregnancy but returned to her normal level of tolerance after
delivery.
Panel Discussion and/or
Question Period
Parents kept four
professionals busy answering questions. The panelists were: Dr. Elsas, Sandy
Van Calcar R.D., Alice Mazur R.N., P.N.P., and Doreen Anderson R.N.
Saturday a.m.- June 6
MSUD Family Newsletter
Update
by Joyce Brubacher & Peter Shaffer
Peter explained some
statistics about the organization.Ê
Joyce encouraged sales of our MSUD cookbooks and forgot all the other
things she meant to talk about!
Low Protein Bread &
Rolls Baking Demonstration by Shayla Brubacher
Shayla explained how to
use an Hitachi bread making machine.Ê
With the help of a friend, she demonstrated the machine by putting in
the ingredients and serving fresh warm bread 4 hrs. later.Ê She had some previously made low protein
pretzels and bread sticks to sample.
Teen Workshop held by Doreen Anderson
and Helen Phillips in an area adjoining the conference room
This was an opportunity
for the older children with MSUD to discuss and compare diets and
experiences.Ê They learned that all
persons with MSUD share a love for potatoes, their number one diet staple.
Psychological Testing:
What Does It Mean?
by Jo-Ann Finegan, Ph.D., Clinical Psychologist, Department of Psychology,
Hospital for Sick Children, Toronto
Little has been written
about psychological testing of persons with MSUD, possibly because individual
medical centers have so few patients.Ê
Tests are yardsticks and psychological assessment is more than just test
results.Ê Dr. Finegan explained testing
in general.
Dietary Workshop:
Feeding the MSUD Child--Parents and Professionals Together by Anna Marie Schaefer,
R.D., MPH.,Ê Pediatric Outpatient
Service, University Hospitals, Ann Arbor, MI
Anna Marie covered these
areas in this workshop: Model (diagram), Goals, Pediatric Neurology Clinic
Experience, Parent Experiences, and Creating Variety in the MSUD Diet for
School Age Children.
Language Disabilities
and Speech Pathology
by Sue Scott, Speech Pathologist, Richmond Hill, ON
ãSpeech-Language
Pathologists work with all age groups to improve clientsâ speech, language, and
swallowing skills.Ê Some Speech-Language
Pathologists also work to improve feeding skills.äÊ So begins a paper passed out by Sue which covers much of her
talk.Ê This handout provides definitions
of terms, gives risk factors for those with MSUD, explains speech, language and
swallowing/feeding intervention, and what parents can do to encourage language
development.
Humor in Chronic Illness
Workshop
by Arlette Lefebre, M.D., Child Psychiatrist, Associate Professor for
University of Toronto, Hospital for Sick Children, Toronto
Dr. Lefebre gave a
humorous talk with a serious message.Ê
Her handout covers how to build your own humor resources, organize and
start using your resources, use humor for a variety of reasons, and develop
humor resources at work.Ê She also
includes material on using computers with modems to access public forums.
FIELD
TRIAL AT SYMPOSIUM
Louis J. Elsas, M.D.
Dr. Louis J. Elsas and Dr. Klein
brought equipment for a study project for which they were looking for volunteers.
It was a painless test but not totally tasteless according to the look on some
of the childrenâs faces as they drank their ãtastelessä drink.Ê Dr. Elsas wrote the following summary of
this project for our Newsletter.Ê He
will share with us the final results when the study is finished.Ê This was a simple way for the families to
aid in research.Ê Thanks for the
opportunity, Dr. Elsas.
The Toronto field trial
testing childrenâs ability to oxidize leucine-1-13C to 13CO2
Êwas a great success.Ê Basically this study was designed to answer
the following questions:
1.ÊÊ Can we measure
whole body leucine oxidation with a single oral drink of leucine and analyze
how much is expired as CO2?
2.ÊÊ Can we
differentiate degrees of impaired branched-chain αketo acid dehydrogenase among children with
MSUD?
3.ÊÊ Can we identify
carriers of MSUD among siblings of patients with MSUD?
4.ÊÊ Can we determine
which patients with MSUD will respond to pharmacological doses of thiamine by
sequential analysis of whole body leucine oxidation to expired CO2 ãonä
and ãoffä thiamine?
Background
Dr. Klein and I had
worked on a stable isotope method (13C) to study whole body leucine
oxidation using intravenous infusions, multiple blood sampling, as well as
sampling breath.Ê Although this clearly
identified the whole bodyâs oxidation potential for leucine, it was too
invasive (too many blood sticks) to make it clinically useful.Ê Only 20% of branched-chain αketo acid dehydrogenase
is activated in cultured dermal fibroblasts and since most of the bodyâs
branched-chain amino acids are catabolized by liver, muscle, heart, and kidney,
we need a better method to assess whole body leucine oxidation.Ê Hopefully such a method could be used to
answer questions 2, 3, and 4 and predict the degree of dietary restriction of
branched-chain amino acids in babies with MSUD.
Results
Twenty-eight families
and forty-six children volunteered for the non-invasive (no sticks) breath test
before the Toronto meeting.Ê Affected
children with MSUD had reduced amounts of 13CO2 recovered
in their breath tests compared to their unaffected siblings.Ê We have incomplete data as yet, but it
appears that the more severe the requirement for dietary restriction, the lower
the 13CO2 recovery in the childâs breath.Ê Therefore, this test has the makings of a
method to predetermine how much dietary restriction of branched-chain amino
acids will be required.Ê Among eight
children whom we tested ãonä and ãoffä thiamine here at Emory, three clearly
had increased whole body leucine oxidation ãonä thiamine while five did
not.Ê The three ãthiamine-respondersä
also had a clinical response and required less dietary leucine restriction ãonä
thiamine.
We are still evaluating
whether the carrier state can be determined in unaffected siblings by this
breath test.Ê The preliminary data says,
ãyes.äÊ It is clear that obligate
heterozygous parents have reduced whole body leucine oxidation compared to
adult controls.Ê We do not yet have
enough age matched normal childhood controls.
So, in summary, the
preliminary answers to our four questions are, ãyesä.Ê We need more clinical information on those of you who have not
completed the clinical survey form and to develop more childhood-aged control
data.
Thank you very much for
your hospitality and enthusiasm.Ê I look
forward to working further with all of you to best care for our kids challenged
by MSUD.
COMMENTS
FROM A PARENT
Sandy Bulcher
Regarding the 1992
Symposium, our family had a wonderful time!Ê
The Sullivans and Toths obviously worked very hard in preparation for
the Symposium and it showed.Ê It is
really special to watch the fellowship that takes place between the
children.Ê It is also great to be able
to communicate about MSUD where people know what you are talking about (instead
of the usual confused response that we are all used to).Ê It struck me that talking about MSUD there
is like talking about the common cold to the general public.Ê I was able to get several specific dietary
questions answered, which proved to be very helpful.
Dr. Menkes:Ê It was fascinating to hear the process that
he and his associate went through to determine the source of the maple syrup
smell of the urine.Ê Everyone felt a
sense of gratitude toward him for all that he has done for MSUD.
Dr. McInnes:Ê He mentioned that some doctors believe that
the level of keto acids is what causes brain intoxication instead of the
leucine level.Ê Also, it was interesting
to learn how much the leucine level can vary from patient to patient and even
with the same illness and the same patient.Ê
(We are starting to find this is true with our son, Jordon).
Dr. Elsas:Ê He suggested that if we are traveling, we
can contact his office to find out where other metabolic centers are
located.Ê I hadnât realized that
children with MSUD could lead a fairly normal life with 5-10% enzyme
functioning.Ê The leucine oxidation test
was interesting and hopefully will be helpful to all of us.
POST
CONFERENCE FOLLOW-UP
Anna Toth wrote a letter to the
Newsletter families on Oct. 15, telling about the birth of the baby she was
expecting in June, and she included other information from the Toths and
Sullivans who hosted the Symposium.
Time does fly. My new
baby is now four months old and I canât believe the conference has come and
gone.Ê Daniel Robin Nicholas Toth was
born on Fatherâs Day, June 21, 1992; a week late, but better than having been a
week early at the conference.Ê He is a
beautiful, healthy boy and has given all of us great joy.Ê Thank you for all of your good wishes at the
Symposium.Ê It meant a great deal to our
whole family.Ê I remember when I had
Michael, our MSUD child, I thought my chance of having a full large family was
so limited; only to look around now and, at times, with sheer disbelief realize
all my dreams have come true.Ê
We, the Toths, as well
as Mike and Karen Sullivan, feel that the conference was a real success. The
guest speakers were wonderful.Ê Our
sincere thanks to those who attended and shared with us.Ê We felt the professionals were informal,
warm and very approachable.Ê Many of you
expressed the feeling that meeting Dr. Menkes was a real bonus.Ê Wasnât he just fascinating!Ê It really impressed me that if it werenât
for the curiosity of these dedicated doctors, this disease would not be as
treatable as it is today.Ê Dr. Elsas was
pleased to have a gathering of children with MSUD and their siblings to further
his study.Ê Iâm sure all who
participated are eagerly awaiting the results. ÊHe andÊ Dr. Klein were
interesting and informative.
We were glad the
meeting, meals and lodging were all in the same building.Ê It made it much more convenient for all of
us. We were so encouraged by the feedback that we received on your little
yellow sheets of paper.Ê It would appear
that you all felt the speakers were very fun and interesting, and the food
excellent with a very good variety for the MSUD children. We realize that
without the daycare facility we provided, it would have been impossible for
some of you to attend.Ê With positive
feedback like this, we feel all the effort and the fund raising was well worth
it.Ê It all came together with only a
few difficulties.
To any of the families
who had problems with reservations, etc., again our most sincere
apologies.Ê We tried our best to rectify
any situations that came up.Ê We realize
the facility was small for our meals, but eventually we all ate and ran pretty
much on schedule.Ê You were all very
patient and kind.
As for the helpful
comments for future conferences, we have reviewed them and passed the
information along to those hosting the next conference in Missouri in
1994.Ê Several concerns were
expressed.Ê Some thought the conference
should be held later in the summer÷perhaps mid to late June.Ê Our seating was a little more cramped and
not as convenient as at Montreal.Ê We
realize this, but initially expected a group of about 70 to 100 persons and had
far more.
There was a desire
expressed for some parent panels on personal experiences and ideas to use with
MSUD children of various ages, including how older children dealt with the
disease.Ê (I think we all agree Elio
Canella did a wonderful job expressing his perspective on being a teenager with
MSUD.)Ê Many parents of older children
expressed surprise at advances in research and the new ideas that were
presented.
Thank you for
participating.Ê We truly enjoyed meeting
the families and sharing information.Ê
It was a joy to see all of you, and we hope to see you in 1994.
÷Best wishes from the Toths and
Sullivans
MSUD NEWS
FROM
THE CLINIC
FOR SPECIAL CHILDREN
Amos Fox helped chore as usual on
the family farm this summer.Ê It could
have been quite different for him and his family if it hadnât been for Dr.
Holmes Morton.Ê This article is an
unedited account of Amosâ successful brain surgery as written by Dr. Morton for
this Newsletter.Ê Hopefully what was
learned from this experience will be of value in treating other children with
MSUD.Ê Thank you Dr. Morton for taking
time to share this important information with us.
Last Spring I was asked
by Joyce, Alma and Weaver Fox, and others interested in the case to write about
the hospital management of a 13 year old boy with classical MSUD who underwent
surgery to remove a brain tumor.Ê I have
found it difficult to write a summary of the case because details of his
treatment were complex and my conclusions preliminary.Ê Nevertheless, I think the case raises
important questions about treatment of MSUD which parents, patients, and
physicians who read the MSUD Newsletter should be aware.
DAILY MONITORING OF MSUD
AND RECOGNITION OF UNDERLYING ILLNESSES:Ê
The earliest sign of Amosâ tumor was difficulty with control of his
MSUD.Ê Alma found that the urine DNPH
test was positive regardless of changes in diet which previously brought his
MSUD under control.Ê If Alma had not
used DNPH tests to monitor Amos, and had she not made repeated efforts to
improve his metabolic control, then the diagnosis of the tumor would certainly
have been delayed.Ê As discussed below,
the pressure of the tumor upon the brain stem caused vomiting and such severe
metabolic derangements that without Almaâs careful monitoring I think Amos might
have died from metabolic intoxication before the underlying cause was
discovered.
Although Amosâ tumor was
an unusual cause of loss of metabolic control, his case is an example of the
importance of daily monitoring with DNPH and careful dietary records for the
general health care of these patients.Ê
When a patient who has been under good control with a fixed leucine
intake of 20 mg/kg-day becomes leucine intolerant as shown by repeatedly
positive DNPH tests then their management must immediately be changed and a
reason sought for the loss of metabolic control.Ê More common causes of sudden changes in the leucine tolerance are
painful injuries, viral infections such as influenza, childhood hepatitis,
immunization reactions, hidden dental abscesses, chronic inner ear, sinus or
urinary tract infections.Ê Uncommon but
by no means rare problems such as hyperthyroidism and insulin dependent
diabetes would also cause loss of metabolic control in MSUD patients long
before other signs of these disorders would lead to diagnosis.Ê Monthly or twice yearly blood leucine
measurements are not adequate for early detection of such problems.Ê I have no doubt that careful control (and
records) of daily leucine and caloric intake and routine monitoring of urine
DNPH will decrease the frequency of life-threatening metabolic illness in
children with MSUD and will help early recognition of important underlying
conditions.
LIFE-THREATENING
METABOLIC ILLNESSES PROVOKED BY SURGERY OR INJURY:Ê Surgery or injuries that involve prolonged, stressful, or
painful recoveries are especially dangerous to children who have MSUD.Ê Plans to monitor and manage MSUD must be
made carefully.Ê Throughout Amosâ
hospitalization urine DNPH tests and serum amino acid analysis were done 1-4
times daily as needed to monitor the frequent changes in therapy.Ê Serum branched chain keto-acids were also
measured to study the relationship between the urine DNPH reaction, blood amino
acids, and keto-acids.Ê MSUD
hyperalimentation was started through a secure central venous line before
surgery.Ê His surgery was delayed
until the serum leucine was 5 mg/dl.Ê
Even before his operation Amosâ leucine level was difficult to control
because of the tumor and because of the effects of a steroid called Dexamethasone
which was given to reduce the brain swelling caused by the tumor.Ê Although this steroid is known to stimulate
the breakdown of protein, Amosâ neurosurgeon, Dr. Edward Garitto, felt the
medication was necessary, and I agreed that with careful management of MSUD the
likely benefit of the medication outweighed its risk.
The brain surgery and
the first 12 hours after surgery passed without difficulty.Ê The earliest sign of worsening metabolic
control was increased blood glucose and resistance to the insulin which was
added to keep the blood glucose in the normal range.Ê Over the period 12-24 hours after surgery the DNPH test changed
from clear to cloudy and leucine increased from 6 mg/dl to 10 mg/dl regardless
of MSUD hyperalimentation and high doses of insulin.Ê Although it was possible to prevent further increases in leucine,
I was aware that the nutritional support necessary to control his MSUD was far
greater than expected.Ê In other MSUD
patients, in and out of hospital, I have found that caloric intakes of 1.5-2
times the calculated basal metabolic rate of the patient will stop protein
breakdown and usually steadily lower serum leucine.Ê Amosâ basal metabolic rate when he is well is approximately 28
Cal/kg per day (1000 Cal/day). My initial goals were 60 Cal/kg-day as glucose
and 1 gram/kg-day protein in the form of a MSUD amino acid mixture for
intravenous use.Ê By day #3 after
surgery serum leucine level could just be kept below 12 mg/dl with
hyperalimentation rates of 110 Cal/kg-day and 1.8 g/kg-day of MSUD amino acids
combined with high insulin infusion rates (0.5 units/kg-hour).Ê Dexamethasone was stopped 3 days
after surgery because of my concern about the difficulty of lowering
leucine.Ê Insulin requirements decreased
rapidly over the 24 hours after Dexamethasone was stopped, but the
leucine remained very resistant to change.Ê
In 24 hours leucine could only be lowered from 10 to 8 mg/dl regardless
of a MSUD hyperalimentation rate of 122 Cal/kg-24 hours and MSUD amino acid
mixtures of 1.8 g/kg-24 hrs.
Although it was
increasingly apparent that Amos was in an unusual high catabolic state, I
questioned if the amino acid mixture in the hyperalimentation was for some
reason ineffective÷in retrospect this was not true.Ê To test this idea, on the 6th post-operative day I asked Amos
(who was surprisingly cooperative) to drink 60 oz of MSUD formula (40
Cal/kg-day) and I provided another 35 Cal/kg-day as intravenous glucose.Ê Despite this Caloric intake of 2700 Calories
(2.5 times his normal basal metabolic rate) and the amino acid mixture in MSUD
formula, his leucine increased from 8 mg/dl at 10 AM to 18 mg/dl at 4 AM the
next morning and to 31 mg/dl 14 hours later.Ê
The DNPH test became strongly positive, and he became disoriented and
showed other signs of intoxication.Ê
This was an extremely rapid and dangerous increase in leucine.Ê Hyperalimentation was restarted with glucose
infusion rate of 150 Cal/kg-24 hours, 4 gm/kg-24 hours of the MSUD amino acid
mixture, insulin was used as needed to keep the blood sugar normal, and
infusion of intravenous fat was started.Ê
The total daily caloric was more than 180 Cal/kg-day, nonetheless, his
leucine level was again very difficult to control.Ê Serum leucine decreased only from 31 mg/dl to 28 mg/dl between
day 7 and 8 and Amos continued to show signs of intoxication.
It was apparent that
Amos was in an extreme protein catabolic state which could not be controlled by
the calories, glucose, amino acids in the hyperalimentation solution
alone.Ê The cause and the means to
control the abnormal state had to be found.Ê
I knew that the effects of Dexamethsone upon glucose and insulin
had been gone for several days, blood cultures were negative, there were no
signs of infection in the surgical wound, and even his thyroid function tests
had been checked and were normal.Ê I
reasoned that the abnormal hypermetabolic state must be related to the effects
of surgery upon the brain-stem itself and most likely were caused by
adrenalin-like chemicals released as a result of brain stem irritation or
swelling. Hyperalimentation, intralipid, and insulin were continued and a
medication called Propranolol was given at the same dose used to control
the severe catabolic effects caused by extreme hyperthyroidism. ÊPropranolol at this high dose blocks the
effects of the catacholamines which are adrenalin-like compounds released by
nerves that originate in the brain stem and by the adrenal gland.
Within six hours after
intravenous propranolol was given the leucine level had fallen from 28
mg/dl to 21 mg/dl and continued to fall rapidly÷serum leucine decreased from 28
to 12 mg/dl in the first 24 hours and 12 to 3 mg/dl in the next 24 hours.Ê The urine DNPH test became negative when
serum leucine was 15-12 mg/dl and isoleucine was 3.5-2.5 mg/dl. ÊPropranolol was initially given
intravenously and then was continued as an oral medication.Ê Intralipid was stopped and hyperalimentation
was slowly weaned over three days while MSUD formula and food were
started.Ê His DNPH remained clear and
leucine levels ranged from 1-3 mg/dl until discharge with a daily calorie
intake of 60-80 Cal/kg-24 hours, total protein 0.6 g/kg-24 hours and leucine at
10-20 mg/kg-24 hours.Ê Amos remained on
a well controlled diet and propranolol by mouth throughout his subse- quent
radiation therapy.Ê His DNPH remained
clear and his average serum leucine level over this 3 month period was less
than 4 mg/dl.Ê Now 10 months later he is
well, active, and there are no signs of recurrence of the tumor.
FINAL COMMENTS:Ê Physicians who work in neurological
intensive care units are aware that patients often have severe protein wastage
after brain surgery or injury.Ê I think
Amosâ severe metabolic illness after surgery was similar.Ê I would also speculate that a similar high
catabolic state develops in the final stages of fatal illnesses of MSUD.Ê As brain intoxication worsens and brain
swelling develops, that catacholamines are released from the brain which
stimulate extremely high rates of protein breakdown and rapidly fatal intoxica-
tion.Ê I expect that beyond a certain
stage of illness the metabolic effects of these signals cannot be easily
reversed by MSUD hyperalimentation alone as was seen in Amosâ case.Ê Control of such hypercatabolic states will
require a combination of careful nutritional management and use of
medications that block catabolic signals and stimulate protein synthesis.Ê Insulin and propranolol were used in Amosâ
management and are inexpensive, relatively safe, widely available.Ê Other medications such as growth hormone or
more selective catecholamine or cortisol antagonists may ultimately prove even
more effective.
The rate at which Amosâ
leucine fell between days 9 and 11 was extremely fast÷on day 9 the rate was 16
mg/24 hours, over a 48 hour period the leucine fell from 28 to 3 mg/dl or 12.5
mg/dl per 24 hours.Ê The paper by Dr.
Berry about MSUD hyperalimentation reported a rate of decrease of leucine of
only 4.5 and 6.5 mg/dl per day.Ê In my
opinion this combination of MSUD hyperalimentation and medication to block
catabolic signals will also prove to be more effective and safer than
peritoneal dialysis.Ê The rate of fall
of leucine in Dr. Scriverâs 8 cases treated with combined intravenous and
nutritional therapy and peritoneal dialysis averaged only 4.5 mg/dl - 24 hours
with a range of 1 to 10 mg/dl.Ê I do not
think that Amosâ case could have been managed with peritoneal dialysis.Ê As MSUD hyperalimentation becomes more
widely available, I believe peritoneal dialysis will be considered an obsolete
method of treatment for MSUD.
I have recently treated
another severely intoxicated 6 year old MSUD patient with methods similar to
those used in Amosâ case with similar metabolic results and full recovery.Ê Although encouraged by the results, I must
emphasize that my observations discussed here are preliminary and
unpublished.Ê Other clinical studies
will have to be completed before the approach is accepted as standard therapy.
FAMILY
HISTORY
The following history was written
by Glenda Groff from Pennsylvania, mother of Jordan.Ê She enclosed a photograph of Jordan sitting on the floor with a
box of spilled cereal.Ê He has a very
mischievous look.
On June 29, 1991, our
son Jordan was born.Ê He seemed to be a
healthy child.Ê We returned home from
the hospital the next day.Ê Jordan received
the newborn screening test at 24 hours just before we left.
He never nursed as well
as our daughter had.Ê On July 4th I
first noticed his breathing seemed really irregular.Ê The following day the health care nurse came to our home.Ê She stated that she thought everything
seemed fine.Ê Being reassured, I decided
I must just have a fussy baby.
Saturday morning we
received a call from our family physician, asking a few questions.Ê Little did I know the answers I gave told
him what he needed to know.
Jordan was the first
child picked up through the Pennsylvania state screening program.Ê He was admitted to the Childrenâs Hospital
of Philadelphia.Ê There we began to
learn about these new problems we had to cope with.Ê His highest level was 34 mg/dl Saturday evening.Ê We brought him home 10 days later with a
level below one.
We now had a very
content baby who could hardly get enough to drink.Ê All went well except for a few bouts of flu.
In March he got an ear
infection.Ê This was one of many, we
were soon to find out.Ê We were constantly
going to the doctor and changing medicine, with good results for a short time,
then back again.Ê Doctor Morton gave him
several antibiotic shots, and they would carry him over a few days.Ê We were thankful his levels did not elevate
during this time.
On September 8th we went
to see an ear specialist. We returned the following day and had tubes put in
his ears.Ê He came through the surgery
really well. I gave him the same amount of formula he had been taking.Ê His level remained at 1 mg\dl.Ê Since that he is doing very well and has not
been sick
Developmentally he is
doing great.Ê He began walking at 11
months and itâs been a real chase ever since.Ê
His favorite thing is climbing, the higher the better.
Jordan is doing very
well at this time with his diet. We have graduated him to a sipper cup.Ê But it seems to be just Mom who he will take
it from.Ê French fries, squash, and
applesauce seem to be his favorite foods.
We have learned a great
deal about this disease.Ê Jordan has the
classic MSUD.Ê It really is amazing to
me how little people know about MSUD.Ê
In the Surgical Center, where the tubes were put in his ears, I had to
describe this disease to everyone.Ê
Sometimes the reaction you get is very interesting.Ê This remark came to me from someone, ãOh,
you mean he canât have maple syrup?äÊ So
we are continuing to learn more about MSUD.
We are thankful he is
doing so well and for the insight he gives us into what other families go
through with their special children.Ê We
also are thankful for our 3-year-old daughter, Andrea, who doesnât have this
disease.Ê A special thanks to Dr. Morton
and his staff and all the support we get from the families.
÷May God bless each one of you,
Ernie, Glenda, Andrea, and Jordan Groff
RECIPES
Submitted by Kelly Green,
R.D., Metabolic Nutritionist, Philadelphia, PA
The holidays are
here!Ê This is a time of gatherings with
family and friends.Ê Many times the
gatherings are centered around a meal.Ê
If the celebration is at your family home, you can plan low protein items
into the menu.Ê If you are attending a
gathering at a distant relativeâs or friendâs home, the host or hostess may not
fully understand your childâs special diet.Ê
Here are some suggestions for how to ease into these gatherings:
1.ÊÊ Call ahead to the
host or hostess.Ê You may be able to
closely duplicate menu items with low protein items brought from home.
2.ÊÊ Offer to bring a
low protein item that everyone can sample.
3.ÊÊ Try to keep your
childâs leucine intake to a minimum prior to the event.Ê This will allow for any higher protein item
your child may sample.
Spicy Candied Yams
|
16 oz. can yams or
sweet potatoes, drained |
1/2 tsp. cinnamon |
|
3 T. packed brown sugar |
1/4 tsp. ginger |
|
2 T. margarine or
butter, cut into pieces |
1/4 tsp. cloves |
|
1/2 c. Richâs Coffee
Rich |
2/3 c. (26 gm) mini
marshmallows |
Mash sweet potatoes or
yams in a 1 qt. casserole dish.Ê Stir in
brown sugar, margarine, Richâs Coffee Rich and spices.Ê Top with marshmallows.Ê Bake at 350¡, uncovered for 15 minutes or microwave on 70% power for 5
minutes.Ê Yield: 2 2/3 cups (670
gm)Ê 1 serving is 31 gm (2 tablespoons)
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Basic Pie Crust
|
3/4 c. (83 gm)
Wel-Plan Baking Mix |
1/2 tsp. salt |
|
3/4 c. (83 gm) wheat
starch |
1/4 c .cold water |
|
1/3 c. plus 1 T.
butter flavored Crisco |
|
Combine baking mix,
wheat starch, and salt in a mixing bowl.Ê
Cut in shortening with a pastry blender, or fork, until the mixture
resembles coarse bread crumbs.Ê Dribble
water over dry ingredients, blending in with fork until all of dough clings
together.Ê Form dough into a smooth
ball.Ê Roll dough out to 1/8 inch
thickness in a size circle needed for specific recipe.
Yield: 12 pot pies (25
gm each) or 10 small turnoversÊ (30 gm
each), or five 4 inch diameter pies (60 gm each)
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Pumpkin Pie
1/4 c. (50 gm) canned
pumpkin
1 1/2 tsp. cornstarch
2 T. packed brown sugar
1/3 c. Richâs Coffee
Rich
2 T. (18 gm) cook type
vanilla Jell-O Pudding & Pie Filling Mix
1/2 tsp. pumpkin pie
spice (or combination of cinnamon, nutmeg, & ginger)
4 inch unbaked pie
shell, using low protein pie crust of your choice
Preheat oven to 425¡.Ê Mix
all ingredients in a bowl.Ê Pour into
unbaked pie shell.Ê Bake for 30 minutes.Ê
Yield: 2/3 cups (180 gm) filling
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