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.
Department of Pathology, University of Utah, Salt Lake City, UT, 84108, USA. irene.de-biase@aruplab.com.|ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT, 84108, USA. irene.de-biase@aruplab.com.|ARUP Institute of Clinical and Experimental Pathology, Salt Lake City, UT, USA. irene.de-biase@aruplab.com.
Irene
I
De Biase
Department of Pediatrics, University of Utah, Salt Lake City, UT, 84108, USA.
Krista S
KS
Viau
ARUP Institute of Clinical and Experimental Pathology, Salt Lake City, UT, USA.
Aiping
A
Liu
Department of Pathology, University of Utah, Salt Lake City, UT, 84108, USA.|ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT, 84108, USA.|ARUP Institute of Clinical and Experimental Pathology, Salt Lake City, UT, USA.
Tatiana
T
Yuzyuk
Department of Pediatrics, University of Utah, Salt Lake City, UT, 84108, USA.
Lorenzo D
LD
Botto
Department of Pathology, University of Utah, Salt Lake City, UT, 84108, USA.|ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT, 84108, USA.|ARUP Institute of Clinical and Experimental Pathology, Salt Lake City, UT, USA.|Department of Pediatrics, University of Utah, Salt Lake City, UT, 84108, USA.
Marzia
M
Pasquali
Department of Pathology, University of Utah, Salt Lake City, UT, 84108, USA.|ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT, 84108, USA.|ARUP Institute of Clinical and Experimental Pathology, Salt Lake City, UT, USA.|Department of Pediatrics, University of Utah, Salt Lake City, UT, 84108, USA.
Nicola
N
Longo
Acylcarnitine; Carnitine; Fatty acid oxidation; Long-chain 3-Hydroxy Acyl-CoA dehydrogenase (LCHAD) deficiency; Newborn screening