Overall, acute metabolic decompensation is the most frequent form of presentation in VLCAD-deficient patients, and most patients suffer from the severe cardiomyopathic form with early onset and poor outcome. Myalgia is more severe and episodes more numerous than in CPT2 deficiency 75 (2) a severe childhood form, with early onset of dilated or hypertrophic cardiomyopathy, recurrent episodes of hypoketotic hypoglycemia and high mortality rate (50%–75%) and (3) a milder childhood form, with later onset of hypoketotic hypoglycemia and dicarboxylic aciduria, low mortality, and rare cardiomyopathy. 74 The defect is clinically heterogeneous and can cause three major phenotypes: (1) an acute presentation with exercise-induced rhabdomyolysis and myoglobinuria. 73 It appears to be the most common long-chain FA oxidation defect, with a disease prevalence of up to 1:30,000. VLCAD deficiency 72 has been reported in more than 400 cases. 28 Because of their systemic manifestations, LCHAD and TFP deficiencies are unlikely to be confused with the inflammatory myopathies.įranco Taroni, Cinzia Gellera, in Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease (Sixth Edition), 2020 Clinical features Clinical features include hypoglycemia, hypotonia, dilated cardiomyopathy in the setting of hydroxydicarboxylic aciduria, and a normal blood acylcarnitine profile. 29 It seems to be the only fatty acid oxidation disorder in which blood lactate levels are consistently elevated even when the patient is asymptomatic. TFP deficiency is more severe, with a high risk for early mortality. 28 Enzyme and mutation testing will differentiate isolated LCHAD deficiency from TFP deficiency. 29 The diagnosis is made by finding elevated hydroxyl long-chain acylcarnitines (OH-C16, OH-C18:1, and OH-C18:2) in the acylcarnitine profile. Isolated LCHAD deficiency is a common fatty acid oxidation disorder characterized by long-term complications caused by cardiomyopathy, neuropathy, and retinopathy, with a high risk for rhabdomyolysis associated with stress or exercise. LCHAD resides in a TFP bound to the inner mitochondrial membrane, along with 2-enoyl-CoA hydratase and 3-ketoacyl-CoA thiolase. George Stojan, Lisa Christopher-Stine, in Rheumatology (Sixth Edition), 2015 Long-chain acyl-CoA dehydrogenase deficiency and trifunctional protein deficiency
0 kommentar(er)
