MCAD Deficiency and SIDS

Wed, 28 Jul 1999

If a medical examiner sent out tissues to be tested, how long would it take to get them back? Is there a time frame that this testing needs to be done (for instance, if they parents had a second opinion on the autopsy, would it still be identifiable?)

There is no strong link between SIDS and metabolic diseases. Fatty acid disorders have been linked with sudden death, but these occur primarily in children older than 1-2 years of age, and should be associated with fatty changes in the liver at autopsy. These disorders can be identified from tissue samples (liver) or with urine, and would likely take several weeks for results.

Hope this is helpful.
Dr. Carl Hunt
chunt@MCO.EDU 

August 1997

Metabolic Causes of Sudden and Unexpected Death in Early Life

By: Piero Rinaldo, MD
Associate Professor of Genetics and Pediatrics
Director, Biochemical Disease Detection Laboratory
Yale University School of Medicine, Dept of Genetics
333 Cedar Street New Haven, CT 06520
Phone: (203) 785-7659 Fax: (203) 785-3535
E-mail: Piero.Rinaldo@Yale.edu 

13 May 1997

In reply to the question about whether or not
babies should routinely be screened for MCADD: This is a
complicated issue. Obviously, there are rare disorders for which
mandatory newborn screening takes place, phenyketonuria (PKU) for
example. Why was it decided to screen for this, and not other
disorders which may occur as frequently in the population? I do
not know. Probably one reason is that there is a good test for
PKU, which is simple and inexpensive, and has a high degree of
sensitivity and selectivity. For MCADD, we do not have such a
test. The DNA diagnostic test detects only one of several
specific gene mutations which can result in this disorder. Thus,
the test would, at best, pick up only about 90% of MCADD in the
Caucasian population, perhaps less in other populations. Second,
the test is not one that can currently be run on a mass scale.
Therefore, I do not think we will see MCADD newborn screening in
the near future. It is possible that it may be included on the
list in the future.

Currently, we recommend MCADD testing whenever an infant has a
family history of at least 2 SIDS; 1 SIDS and 1 apnea; or 2
apnea. For those parents who do not fit one of the above
categories, but who are concerned about this, you can discuss it
with your pediatrician, and the test can be ordered. In all
likelihood, not many will be positive.

For interest, I should add that we also did a study of metabolic
errors in infants with severe apneas. We did find an increased
incidence of metabolic disorders dealing with the conversion of
fats to energy (of which MCADD is one example). However, in our
study, none of the specific metabolic disorders turned out to be
MCADD, though they would have similar potential risks. Thus,
screening these babies only for MCADD would not have picked up
any of those with the disorder. I guess this is another way of
saying that the diagnosis of metabolic disorders, which might
conceivably cause sudden death in infants, remains a complex
process requiring mutliples tests and expertise to guide which
tests to perform.

I hope this helps. Thanks.

Thomas G. Keens, M.D.
Children's Hospital Los Angeles

13 May 1997

I would agree that if a child died
at 22-months of age (not characteristic for SIDS, more
characteristic for metabolic disorders, especially MCADD), and if
he/she had a fatty liver on autopsy, then subsequent babies
should be screened for MCADD and other metabolic disorders. In
our study of MCADD in SIDS in Los Angeles County, we were able to
extract DNA from the preserved liver tissue which was obtained
from the SIDS victims. We could extract the DNA from babies who
died as much as 6-years earlier. So, if there is reason to test
a baby who died from "SIDS" for MCADD, this would be a good place
to try and get a tissue sample. It only takes a few grams of
tissue (1 gram = 1/30th of an ounce). However, to keep this all
in perspective, the vast majority of babies who die from SIDS do
not have MCADD. Remember, we found zero MCADD in 1200 SIDS
victims in Los Angeles County.

I hope this helps. Thank you.

Thomas G. Keens, M.D.
Children's Hospital Los Angeles

Date: Wed, 30 Apr 1997

MCAD deficiency is a rare "inborn error of metabolism". In this
case, certain fats can not be broken down and metabolized into
energy. During times of stress (illness, fasting, fever, etc.),
when the metabolic rate is high and/or energy stores from food
are low, the body is not able to convert fats into sugar, and
patients with this disorder can become very ill, and even die.
Usually, it affects children older than the typical SIDS age, and
the 23-month age of death described by Lisa Hunt is typical.

Theoretically, MCAD deficiency could cause sudden death in
infants which might go undetected at autopsy. However, there are
probably signs indicating MCAD deficiency (rather than SIDS) that
would be picked up by pathologists. About 10-years ago, a number
of scientists hypothesized that SIDS might be due to MCAD
deficiency. A number of studies were performed, including one
by us in Los Angeles. We performed genetic (DNA) testing on
pieces of liver tissue from all SIDS babies in Los Angeles County
for the previous 6-years (about 1200 deaths). We did not find
one case of MCAD deficiency. Thus, MCAD deficiency is rarely a
cause of "SIDS".

MCAD deficiency is rare, occurring in about 1 in every 17,000
births, compared to SIDS which occurs in 1 in every 1000 births.
It should be considered in families where more than one baby has
had a problem, like SIDS, apnea, shock, etc. However, it would
be very unlikely to show up in families where one SIDS death is
the only problem.

Thomas G. Keens, M.D.
Children's Hospital Los Angeles

A number of years ago, the late Professor David Read for Sydney, Australia, a prominent researcher in respiratory control with interests in SIDS, hypothesized that SIDS might be caused by a group of metabolic disorders, of which MCAD Deficiency (MCADD) is the most common. MCAD is a naturally occurring enzyme in cells which breaks down fats so that can be used for energy. The absence of this enzyme is only a problem in relative fasting or starving states, when there is not enough sugar to nourish the cells of the body. Ordinarily, the cells would break down fats to convert them to sugar, but MCADD prevents this from happening. It has been suggested that if an infant has a fever (high metabolism) and is sick (not eating), then MCADD may result in an apneic episode, and possibly even death. MCADD is inherited as an autosomal recessive disorder. This means, IF each parent is a carrier, there is a one-in-four chance of each baby having MCADD. However, the chance of a person being an MCADD carrier is very low. MCADD is uncommon (about 1 in 7500) as opposed to SIDS, which is very common.

There are a few problems with the theory that MCADD explains most SIDS.

1. MCADD is much rare than SIDS.
   
2. MCADD usually causes symptoms beginning at about 6-12 months of age, and they are more likely to be a problem in the second year of life.
   
3. SIDS does not always occur in a "fasting" state.

We were able to perform a study of all the babies who died from SIDS in Los Angeles County over a 6-year period of time, about 1300 babies. We were able to obtain a small piece of liver tissue which was stored from the autopsy of each infant and run DNA testing for MCADD. None of the infants who died from SIDS had MCADD. Therefore, we believe that MCADD is not a common cause of SIDS.

Presumably, pathologists should be able to distinguish these types of metabolic disorders from SIDS at autopsy because they would result in increased fat stored in the liver. However, the distinction may not be obvious, especially if the pathologist doing the autopsy is not thinking of this as a possibility.

Consequently, I do not think that performing MCADD testing will be helpful in the classical SIDS infant, as your child is unlikely to have died from MCADD.

When is MCADD testing indicated? If there is any family history of SIDS besides your own child, MCADD testing may be more likely. Similarly, if there is a family history of apnea, seizures, etc., MCADD testing may be helpful. We did find an increased incidence of metabolic disorders in infants who presented with severe apnea (ALTE) which required full CPR and which did not resolve like the usual clinical course. This would be another indication.

Finally, a note to physicians: In this latter study, we found that the serum ammonia level was an excellent screening test for the presence of metabolic errors of beta oxidation of fatty acids (of which MCADD is the most common). If the serum ammonia is normal, none of the ALTE babies we studied had a metabolic disorder.

Thomas G. Keens, M.D.
Children's Hospital Los Angeles

Reprinted with permission

2/26/96

Has anyone heard about the gene testing done at Washington University in St. Louis? After our son died, my husband and I were approached about taking a genetic test. I don't remember which gene it was. We haven't done anything about it. Supposedly *they* have linked 5% of SIDS deaths to a mutation of this particular gene. We had a copy of a paper done on this research, but have misplaced it. We are interested to have more info. on this research. Please respond if you have any info. that might help.

Not all SIDS infants undergo extensive genetic testing. These researchers have reported the result of extensive genetic testing on 100 or so infants that died of SIDS and found that some of these actually had this genetic abnormality called MCAD deficiency or medium chain acyl diglyceraldehyde deficiency. This is a fatty acid disorder that can result in the sudden unexpected death of an infant. Infants who have been identified as having this disorder and have died from it have not died of SIDS. They died from MCAD deficiency and subsequent pregnancies can be tested. The total number of infants that may have died from MCAD deficiency but mistakenly called SIDS was initially felt to be as high as 5% but I think this number is too high.

J D DeCristofaro, MD
Infant Apnea Program
Stony Brook, NY