The genetic, biochemical, and clinical features of patients with mitochondrial trifunctional protein (TFP) deficiency, a type of long-chain fatty acid oxidation disorder (LCFAOD), following the introduction of newborn screening in the Netherlands in 2007 were presented at the 2023 lecture series of the International Network for Fatty Acid Oxidation Research and Management (INFORM).
According to this, a total of 13 patients with TFP deficiency were identified. Of these, 7 had isolated long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiency, 5 had generalized TFP deficiency, and 1 had isolated long-chain 3-ketothiolase (LCKAT) deficiency.
Read more about the symptoms of LCFAOD
Of the 13 patients, 2 were missed by newborn screening. All patients with LCHAD deficiency, 1 of whom was missed by newborn screening but diagnosed clinically, and 1 with generalized TFP deficiency who was also diagnosed clinically, were alive.
The remaining 4 patients with generalized TFP deficiency and the patients with LCKAT deficiency developed cardiomyopathy and died within 1 month and 13 months of life, respectively.
The patients who survived did not develop symptomatic hypoglycemia. However, they had reversible cardiomyopathy and rhabdomyolysis.
Of the patients with LCHAD deficiency, 5 developed subclinical neuropathy and/or retinopathy.
All patients with TFP deficiency were homozygous or compound heterozygous for HADHB gene variants. All patients with LCHAD deficiency had HADHA variants, with at least 1 allele carrying the common c.1528G>C (p.Glu510Gln) variant. The patient with LCKAT deficiency was compound heterozygous for the HADHB gene variants c.182G>A (p.Arg61His) and c.1289T>C (p.Phe430Ser).
The researchers concluded that patient outcomes were highly variable, ranging from severe neonatal cardiomyopathy to muscle symptoms induced by febrile illness. This suggests that there is a need for accurate classification of different types of TFP deficiency.
They said that newborn screening allows the prevention of symptomatic hypoglycemia, but the treatment options that are currently available are not able to treat cardiomyopathy and prevent long-term complications. Newborn screening also failed to identify patients with milder disease due to normal acylcarnitine profiles.
Schwantje M, Fuchs S, de Boer L. Genetic, biochemical and clinical spectrum of patients with mitochondrial trifunctional protein deficiency identified after introduction of newborn screening in the Netherlands. Poster presented at the International Network for Fatty Acid Oxidation Research and Management (INFORM) 2023 lecture series: April 17, 2023; Virtual.