What Is Multiple Acyl-CoA Dehydrogenase Deficiency?
Multiple Acyl-CoA dehydrogenase deficiency is a rare inherited metabolic disease with gene defect causing disorder of fatty acid oxidative metabolism in mitochondria and further generating a series of clinical symptoms, which belongs to autosomal recessive genetic disease.
What Is The Cause Of Multiple Acyl-CoA Dehydrogenase Deficiency?
Mitochondrial fatty acid β oxidation is an important energy source in the human body, and electron transport flavoprotein (ETF) or flavoprotein dehydrogenase (ETFDH) is the key transporter for electron transport in the mitochondrial respiratory chain. ETFs are made up of two subunits, ETFs and ETFs.
Mutations in the genes encoding ETFA, ETFB, and ETFDH lead to blocked oxidative phosphorylation in the mitochondria, leading to disorders in the metabolism of fatty acids, branched-chain amino acids, vitamin B, and energy, and the deposition of metabolites, causing a host of symptoms.
Multiple acyl-coa DEHYDROGENASE DEFECIENCY is common in neonates.
What Is The Symptoms Of Multiple Acyl-CoA Dehydrogenase Deficiency?
There are three main types of MADD, and their respective clinical manifestations are described below.
Type Ⅰ of MADD: Neonatal onset with congenital malformations
Neonatal onset type is often fatal, can be manifested as metabolic crisis (including metabolic acidosis, hypoglycemia, hyperammonemia), multisystem involvement (hypotonia, cardiomyopathy, hepatomegaly), the excretion of a large number of fatty acids and amino acids intermediate metabolites, sweaty feet like body odor, coma, sudden death.
Some with congenital malformations, including enlarged polycystic kidney, bassinet foot, lower abdominal muscle loss, hypospadias and penile recurvation, hypotonia, cerebral cortex dysplasia, colloid hyperplasia and head and face deformity.
Type Ⅱ of MADD: Neonatal onset without congenital malformations
Late-onset MADD differs greatly in onset age and symptoms, and is not accompanied by congenital malformations. However, it has a lifelong risk of acute decompensated attack, which can be manifested as intermittent vomiting, dehydration, hypoglycemia, acidosis, and consciousness disorders. Infection, fever, surgery, weight loss, alcohol consumption, pregnancy, etc. can induce acute decompensated attack.
Type Ⅲ of Late-Onset MADD
The late onset was mostly accompanied by symptoms of chronic myopathy, and some of them were of vitamin B2-dependent type. The older may have hepatomegaly or lipid-depositing myopathy.
How To Check Multiple Acyl-CoA Dehydrogenase Deficiency?
The clinical diagnosis of MADD is difficult due to the high heterogeneity of its clinical manifestations.
The possibility of this disease should be considered in the clinical cases of anion gap-elevation metabolic acidosis combined with lactic acidosis, hypoketotic hypoglycemia, and hyperammonemia with the odor of sweaty feet.
We will further improve biochemical tests and imaging tests to identify metabolism and organ function, and improve plasma acyl carnitine tests and urine organic acid tests to identify abnormal fatty acid and amino acid metabolism.
Diagnosis depends on the detection of the causative gene.
How To Prevent Multiple Acyl-CoA Dehydrogenase Deficiency?
MADD is a genetic disorder that warrants prenatal genetic testing and neonatal screening for those with a clear family history. At the same time, patients should avoid infection, fever, surgery, weight loss, drinking and other stress factors in life, to avoid increasing the risk of acute attack of the disease, and should be closely monitored during pregnancy.
How To Treat Multiple Acyl-CoA Dehydrogenase Deficiency?
MADD is currently incurable but can be controlled as follows:
Acute decompensation should limit protein and fat intake, with intravenous glucose, and levocarnitine to promote the excretion of toxic metabolites, while closely monitoring heart, liver, and kidney function.
Patients with late onset muscle involvement are advised to take vitamin B2 orally for life.
Other combination therapies include avoidance of prolonged starvation, supplementation of L-carnitine when combined with carnitine deficiency, and coenzyme Q10 for patients with MADD who have an ETFDH mutation and are combined with coenzyme Q10 deficiency.
MADD prognosis varies significantly according to the different clinical types and timeliness of treatment. Most of the neonatal types have poor prognosis, high mortality, late onset and active treatment, and the prognosis is relatively good.