Metabolic cardiomyopathy associated with a compound heterozygous variant in NAD(P)HX dehydratase: a case report and literature review.

Background: Metabolic cardiomyopathy is characterized by structural and functional changes to the heart and interstitial fibrosis without coronary artery disease or hypertension. Inborn metabolic defects are a common cause of cardiomyopathy in children. There are more than 40 kinds of inborn metabolic defects that cause cardiomyopathy. The heart is one of the most metabolically active organs in the human body. Metabolic disorders may lead to insufficient myocardial energy production, and unwanted metabolites may be produced, which may cause spontaneous chemical damage in the body. Specific metabolic repair enzymes are required to remove accumulated metabolites. The metabolite repair enzyme NAD(P)HX dehydratase (NAXD) is a key enzyme that combats the accumulation of damaged metabolites. It specifically acts on the S exome of NAD(P)HX, restoring NADHX and NADPHX to the functional cofactors NADH and NADPH, respectively. NAD(P)H plays a central role in many biochemical processes, including key oxidation-reduction reactions related to energy production. Patients with NAXD mutations develop severe systemic multisystem impairment after febrile illness that is mainly characterized by severe psychomotor regression with recurrent skin lesions and death. However, cardiomyopathy caused by this gene mutation has rarely been reported.

Case description: This paper reported a patient with a novel NAXD gene compound mutation whose condition deteriorated sharply after febrile illness, causing heart failure, cardiogenic, and ultimately death.

Conclusions: This is one of the few cases of metabolic cardiomyopathy caused by a compound heterozygous NAXD mutation in China.