LCHAD (Long-chain 3 hyroxyacyl CoA Dehydrogense) deficiency is a genetic syndrome with many similarities to MCAD deficiency. Like MCAD, it is caused by an enzyme defect in the beta-oxidation cycle. This results in an inability of the body to break down fatty acids into a usable energy source. LCHAD deficiency can present in many ways, such as hypoglycemia, lethargy, SIDS, or Reye-like syndrome. LCHAD deficiency can also cause a child to have poor muscle tone (hypotonia) and problems with the functioning of the heart (cardiomyopathy). As with many inborn errors of metabolism, LCHAD deficiency is inherited as a recessive genetic condition, so there is a 25% chance of recurrence with each pregnancy. Unlike MCAD deficiency, LCHAD deficiency can cause medical complications during pregnancy for the mother of a child who will have LCHAD deficiency.
People who are carriers for MCAD deficiency have no medical complications from being a carrier, since they have one copy of the gene which produces an enzyme which works correctly [Note from Deb: Several of our carrier MCAD and LCHAD parents HAVE experienced symptoms so this statement is not a blanket statement for all carriers.]. Usually a carrier of LCHAD deficiency will not have medical problems either. However, women who are carriers of LCHAD deficiency may have problems during a pregnancy, if the unborn child has LCHAD. These problems may include: anorexia, vomiting, abdominal pain, and jaundice during the third trimester of pregnancy. If untreated, it can cause liver failure in the mother. This may result in the need for liver transplant or death. These complications are called maternal acute fatty liver of pregnancy or AFLP syndrome. It is not known why women have these complications during pregnancy, or why the problems occur only when the fetus has LCHAD deficiency.
The treatment for LCHAD deficiency is similar to the treatment for MCAD. Like MCAD, an infant or child should avoid fasting. Illness in the child, such as the flu, may necessitate medical treatment or hospitalization for the child. Carnitine, often prescribed for MCAD, is usually not given to a child with LCHAD deficiency. (Note from Deb on carnitine use: For many of our LCHAD families in this Group, however, Carnitor IS prescribed—each situation must be evaluated individually). LCHAD children are also usually given an MCT (medium chain triglycerides) oil supplement to be used within their diet.
LCHAD deficiency was discovered in 1989. The gene for LCHAD has recently been found and the different alterations (mutations) in the gene are being characterized. One laboratory which is looking for mutations in the gene is Dr. Arnold Strauss' lab at Washington University School of Medicine in St. Louis (Note: Dr. Strauss is presently at Cincinnati Children's Hospital, 2008). Investigators in the lab have also found mutations in the gene which causes MCAD deficiency.
Recently, the genes of 3 children with LCHAD, all of which whose mothers had AFLP, were analyzed. In the 6 copies of the gene (2 copies in each of the 3 children), 5 copies were found to have the same change (mutation) of the DNA. This is called the G1528C mutation, named for the location of the mutation. The last gene had a different mutation, called C1132T. The G1528C has been found in other children with LCHAD, so it appears to be a common mutation. Other mutations have also been found by the researchers in the Strauss lab. It is not yet known how many different mutations may occur in the gene, or how common any of already identified mutations will be.
Identification of the mutation allows for accurate diagnosis of the LCHAD deficiency, either as a newborn or prenatally. This may be important so the treatment of the newborn can begin in the newborn period, before the child has a potentially life-threatening episode. It may also help to recognize which pregnancies are at risk for maternal complications of AFLP. Early treatment during the pregnancy may reduce the severity of maternal complications.
At this time, the work in Dr. Strauss' lab is being done at a research level. He hopes that in the near future, some of this testing will be available as a clinical test. Further studies will continue to identify mutations so that information will become available about frequency of the different mutations. This will allow for increased accuracy in diagnostic and carrier testing. Dr. Strauss is committed to helping families where there is a question about the diagnosis of MCAD or LCHAD deficiency and would be glad to evaluate DNA samples if there is a reasonable suspicion of one of these conditions.
Summary: LCHAD deficiency is a newly identified genetic syndrome caused by a deficiency of an enzyme in the beta-oxidation cycle. Since both MCAD and LCHAD are caused by enzyme deficiencies in the same metabolic cycle, they have many of the same medical symptoms, such as hypoglycemia, lethargy, and in severe cases, may first present as SIDS.
Treatment for each is both similar and different. Fasting should be avoided and illnesses may precipitate complications. Individual treatment plans should be coordinated by a physician with expertise with these syndromes. The gene for LCHAD deficiency was recently identified and research is currently looking for mutations in the gene. This will allow for earlier diagnosis and, therefore, better and earlier treatment.
Source: Provided by Rachel Slaugh, a genetic counselor from Washington University School of Medicine in St. Louis, Missouri
Reprinted from the MCAD Communication Network newsletter, June, 1995