Diagnosis, Treatment, and Clinical Outcome of Patients with Mitochondrial Trifunctional Protein/Long-Chain 3-Hydroxy Acyl-CoA Dehydrogenase Deficiency
Deficiency of the mitochondrial trifunctional protein (TFP) and long-chain 3-Hydroxy Acyl-CoA dehydrogenase (LCHAD) impairs long-chain fatty acid oxidation and presents with hypoglycemia, cardiac, liver, eye, and muscle involvement. Without treatment, both conditions can be life-threatening. These diseases are identified by newborn screening (NBS), but the impact of early treatment on long-term clinical outcome is unknown. Moreover, there is lack of consensus on treatment, particularly on the use of carnitine supplementation. Here, we report clinical and biochemical data in five patients with TFP/LCHAD deficiency, three of whom were diagnosed by newborn screening. All patients had signs and symptoms related to their metabolic disorder, including hypoglycemia, elevated creatine kinase (CK), and rhabdomyolysis, and experienced episodes of metabolic decompensation triggered by illness. Treatment was started shortly after diagnosis in all patients and consisted of a diet low in long-chain fats supplemented with medium chain triglycerides (MCT), essential fatty acids, and low-dose carnitine (25 mg/kg/day). Patients had growth restriction early in life that resolved after 2 years of age. All patients but the youngest (2 years old) developed pigmentary retinopathy. Long-chain hydroxylated acylcarnitines did not change significantly with age, but increased during acute illnesses. Free carnitine levels were maintained within the normal range and did not correlate with long-chain hydroxylated acylcarnitines. These results show that patients with LCHAD deficiency can have normal growth and development with appropriate treatment. Low-dose carnitine supplements prevented carnitine deficiency and did not result in increased long-chain hydroxylated acylcarnitines or any specific toxicity.
KeywordsAcylcarnitine Carnitine Fatty acid oxidation Long-chain 3-Hydroxy Acyl-CoA dehydrogenase (LCHAD) deficiency Newborn screening
This work was supported by the ARUP Institute for Clinical and Experimental Pathology®.
- IJlst L, Wanders RJ, Ushikubo S, Kamijo T, Hashimoto T (1994) Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of the major disease-causing mutation in the alpha-subunit of the mitochondrial trifunctional protein. Biochim Biophys Acta 1215:347–350CrossRefPubMedGoogle Scholar
- IJlst L, Ruiter JP, Vreijling J, Wanders RJ (1996) Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a new method to identify the G1528C mutation in genomic DNA showing its high frequency (approximately 90%) and identification of a new mutation (T2198C). J Inherit Metab Dis 19:165–168CrossRefPubMedGoogle Scholar
- Kuczmarski RJ, Ogden CL, Grummer-Strawn LM et al (2000) CDC growth charts: United States. Adv Data 314:1–27Google Scholar