3-Methylglutaconyl-Coenzyme-A Hydratase Deficiency and the Development of Dilated Cardiomyopathy

Abstract

A 25-year-old Canadian male with a history of 3-methylglutaconyl-coenzyme-A hydratase deficiency, also known as 3-methylglutaconic aciduria type I, a very rare inborn error of metabolism, presented with respiratory distress, nausea, vomiting and signs of multisystem organ failure due to a suspected underlying infectious process. An electrocardiogram revealed bilateral atrial enlargement and an elevated brain natriuretic peptide on the initial laboratory studies, which prompted a more thorough cardiac workup. The transthoracic echocardiogram revealed a dilated cardiomyopathy with severe systolic dysfunction. The deficient enzyme present in this patient is involved in the pathway of leucine catabolism and is particularly important in various tissues for energy production and sterol synthesis. The dilated cardiomyopathy in this patient possibly had a variety of potential mechanisms including: a mitochondrial myopathy due to the deficiency of this enzyme leading to a defect in energy production inside cardiac myocytes; or a direct toxicity from 3-methylglutaconic acid (3-MGA) and its toxic metabolites; or a cardiac dysfunction due to a variety of other potential mechanisms. In conclusion, this patient’s clinical presentation suggested that 3-methylglutaconyl-CoA hydratase deficiency could cause a severe dilated cardiomyopathy and heart failure.

Closing the gap: an urgent need for newborn screening of organic acid disorders in developing countries

“…32,33 A study on 3-methylglutaconic aciduria (3-MGA) also revealed the progression of cardiomyopathy in OAs. 34 Furthermore, in MMA patients, major secondary complications include intellectual impairment, tubulointerstitial nephritis with progressive renal failure, metabolic stroke, which referes to acute and chronic basal ganglia injury, pancreatitis, growth failure, functional immune impairment, and optic nerve atrophy. 35 Late-onset forms of OAs are less frequent, and these are characterised by recurrent life-threatening episodes of metabolic crises characterised by encephalopathy, vomiting and dehydration.…”

Organic Acidemias: Clinical Presentation in Neonates

“…12 Type I: A rare AR condition caused by 3-methylglutaconyl-CoA hydratase deficiency. 123 This enzyme converts 3-methylglutaconyl-CoA to 3-hydroxy-3-methylglutaryl-CoA, which is essential in leucine degradation. These patients show high levels of 3-methylglutaconic acid, 3-methyl glutaric acid, and 3-hydroxyisovaleric acid in urine.…”

3-Methylglutaconic Aciduria Type I Due to AUH Defect: The Case Report of a Diagnostic Odyssey and a Review of the Literature

“…Patients affected by this disease manifest a wide range of clinical signs, ranging from no or mild symptoms [8,9] to mild neurological impairment [10,11], acute encephalopathy [12][13][14], severe encephalopathy with basal ganglia involvement [15,16], and slowly progressive leukoencephalopathy presenting in adulthood [17][18][19][20]. Dilated cardiomyopathy [21], central precocious puberty, attention deficient hyperactivity disorder, learning disability, and white matter alterations on magnetic resonance imaging [22] have also been described.…”