Early cardiomyopathy without severe metabolic dysregulation in a patient with cblB‐type methylmalonic acidemia

Abstract

Background Cardiomyopathy is a known complication of organic acidemias but generally thought to be secondary to poor metabolic control. Methods Our patient was found through biochemical testing and Sanger sequencing to harbor an Icelandic founder mutation: NM_052845.4(MMAB):c.571C > T(p.Arg191Trp), leading to an early presentation (4 h after birth) of cblB‐type methylmalonic acidemia (MMA). Biochemical testing of this patient suggested B‐12‐responsiveness and thus the patient was treated with cyanocobalamin throughout life. Informed parental consent was obtained for this report. Results Our patient had three metabolic decompensations in her life (at birth, at 1 month, and at 5 months). The first decompensation was probably linked to stress of delivery, second to rhinovirus infection, and third by co‐infection of norovirus and enterovirus. At 3 months, the patient was noted to be tachypneic, although this was attributed to her underlying metabolic acidosis. At 5 months and 10 days, the patient was admitted with minor flu‐like symptoms but developed severe diarrhea in hospital and upon rehydration had cardiac decompensation and was found to have undiagnosed dilated cardiomyopathy. Although, patient was treated aggressively with dextrose, hemodialysis, levocarnitine, and vasoactive agents, there was limited response to medications to treat cardiac failure, and eventually the patient passed away before turning 6 months old. Conclusions Other than these three mild decompensations, patient had very good metabolic control, thus demonstrating that even without frequent metabolic decompensation, cardiomyopathy can be an observed phenotype in cblB‐type MMA even very early in life, suggesting that this phenotype may be independent of metabolic control.

How guideline development has informed clinical research for organic acidurias (et vice versa)

“…Not only are there novel therapeutic approaches that will directly influence the next revision of the MMA/PA guidelines, there is also evolving knowledge on potential complications of existing therapies, including the use of metronidazole that was linked to the development of peripheral neuropathy 98,99 . Moreover, unanticipated long‐term complications may occur, including the development of liver neoplasms 100 or the occurrence of cardiomyopathy not only in PA but also MMA 76,101 . These novel developments warrant continuous evaluation of available evidence to revise guidelines but also to motivate detailed long‐term studies to precisely delineate the effects of current and novel treatment modalities.…”

“…98,99 Moreover, unanticipated long-term complications may occur, including the development of liver neoplasms 100 or the occurrence of cardiomyopathy not only in PA but also MMA. 76,101 These novel developments warrant continuous evaluation of available evidence to revise guidelines but also to motivate detailed long-term studies to precisely delineate the effects of current and novel treatment modalities.…”