HADHA-related disorders, including long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) and mitochondrial trifunctional protein deficiency (MTPD), are inherited conditions in which the body lacks sufficient amounts of the enzyme(s) needed to turn certain fatty acids from food and body fat into energy. This process, called fatty acid oxidation, normally breaks down fatty acids stepwise until they can be turned into usable energy. Enzyme deficiencies interrupt this process, allowing fatty acids to build up in the body and damage various organs and body tissues.
HADHA is responsible for three enzyme functions in the final steps of fatty acid oxidation. HADHA-related disorders can be divided into two main categories: LCHAD which results from deficiency in just one enzyme and MTPD which includes deficiencies of all three enzymes.
The symptoms of LCHAD and MTPD are overlapping and variable with some individuals severely affected and some more mild forms. Most often, the symptoms begin in infancy or early childhood when affected children may begin to display changes in behavior, poor appetite or feeding difficulties, lack of energy, muscle weakness and developmental delays.
Children with these disorders may experience acute episodes characterized by low blood sugar and increased amounts of harmful substances in the blood. If untreated, they are at high risk for life-threatening heart and breathing problems, comas, seizures, and sudden death. These episodes can be triggered by stresses on the body such as going a long time without eating, illness and infections, or strenuous exercise. Some children may not have symptoms between these episodes, however, repeated crisis events can lead to brain damage and intellectual and developmental disabilities.
Older children and adults may develop muscle pain, a breakdown in muscle tissue, and problems with the nerves in their arms and legs. Some people with LCHAD and MTPD do not have the classic symptoms and may only have the muscle pain and weakness.
Both LCHAD and MTPD have been shown to cause damage to the retina of the eye leading to progressive visual impairment over many years, though this is more commonly associated with LCHAD.
Women carrying a pregnancies that are affected with a HADHA-related disorder are at risk for certain pregnancy complications and should speak with their physician for recommendations.
HADHA-related disorders are rare. Studies in Finland and the United States have shown that the E474Q mutation—which causes the majority of LCHAD deficiency cases—has a carrier rate of approximately 1 in 150 to 200. Based on a carrier rate estimation of 1 in 150, 1 in 90,000 people would be affected by the disease. A study in Estonia found a similar carrier frequency and inferred an incidence of 1 in 91,700.
A study of the results of newborn screening in Germany found 11 cases of LCHAD/MTPD in 1.2 million births. Another newborn screening study in Germany found just 1 case of LCHAD/MTPD in 250,000 babies screened.
The overall incidence in Poland is estimated to be 1 in 118,336, but in specific regions it is more common, up to 1 in 16,900.
The main method of management for LCHAD and MTPD is a special diet and avoidance of fasting. A physician or nutritionist will recommend a diet low in fats and high in carbohydrates, which are easier for an affected person to break down, and a feeding schedule with frequent meals. Often it is necessary to have an additional dietary protocol in place for illness or other stressful times. A physician may also prescribe medium chain triglyceride oil, L-carnitine, or other supplements for additional energy.
Often when symptoms appear in infancy, treatment is not effective because the disease causes irreparable damage to the heart. Untreated, both infant or early childhood onset disease is often fatal or leads to cognitive impairments.
For childhood onset forms, early detection and early treatment can prevent many of the severe complications and allow affected individuals to have typical growth and development. Even with careful treatment, there may still be some episodes of low blood sugar and the possibility of heart, liver, and muscle problems. Recurrent acute episodes of low blood sugar can lead to cognitive impairments over time.
Individuals with later onset disease and symptoms limited to muscle weakness and pain are typically healthy and do not have problems with the heart, liver, or changes in cognitive ability or intellect.
An all volunteer 501c3 non-profit dedicated to providing support, information and international networking for families affected by a Fatty Oxidation Disorder, as well as for professionals working with FOD families.
Director, Deb Lee Gould, MEd
PO Box 54
Okemos, MI 48805-0054
Phone: (517) 381-1940 (8am-8pm EST)
Explanations of an extensive number of genetic diseases written for everyday people by the U.S. government's National Institutes of Health.
A fact sheet produced by a collaborative effort among state agencies in Alaska, California, Hawaii, Idaho, Oregon, and Washington to investigate the financial, legal, ethical, and social implications of programs that screen newborns for certain diseases.
Project coordinator: Lianne Hasegawa CSHN
Department of Health
741 Sunset Avenue
Honolulu, HI 96816
Phone: (808) 733-9039
Counsyl has renamed its products effective July 19, 2017. The Family Prep Screen is now the Foresight Carrier Screen.
The new names now appear on all communications from Counsyl. If you have any questions, please contact Counsyl directly.