Case Report: Dilated cardiomyopathy as the initial presentation in an adult with late-onset CblC defect

TL;DR

A 27-year-old woman with a late-onset CblC defect initially showed dilated cardiomyopathy and kidney issues, highlighting the disorder's varied symptoms and difficult management.

Contribution

This case expands the known phenotypic spectrum of late-onset CblC disorder and highlights its complex clinical course.

Findings

The patient had compound heterozygous pathogenic variants in the MMACHC gene, confirming a cblC-type disorder.

Despite treatment with vitamin B12 and betaine, heart function did not improve.

The patient died from severe complications of COVID-19, including metabolic acidosis and multi-organ failure.

Abstract

Combined methylmalonic aciduria and homocystinuria, cobalamin C (cblC) type, represents the most common inborn error of cobalamin metabolism, caused by pathogenic variants in the MMACHC gene. We report the case of a 27-year-old Chinese woman who presented with dilated cardiomyopathy and renal insufficiency. Blood amino acid and acylcarnitine profiling revealed elevated ratios of propionylcarnitine (C3) to acetylcarnitine (C2) and C3 to free carnitine (C0). Genetic testing identified compound heterozygous pathogenic variants in MMACHC—c.80A > G, p. (Gln27Arg) and c.609G > A, p. (Trp203Ter)—confirming the diagnosis of cblC-type methylmalonic aciduria with homocystinuria. Despite administration of vitamin B12 and betaine, her heart function did not improve. The patient eventually succumbed to severe COVID-19 infection, which led to metabolic acidosis, renal failure, and multi-organ failure. This case underscores the challenging clinical course of late-onset cblC disorder and contributes to its expanding phenotypic spectrum.

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