The interplay of psychosis and non-compliance with fatal outcome in an adult with MSUD

Nadia Falah; Surekha Pendyal; Cina Sasannejad; Allison Gibson; Yu Lin Lee; Marie McDonald; Dwight Koeberl

doi:10.1002/ajmg.a.63637

The interplay of psychosis and non-compliance with fatal outcome in an adult with MSUD

Am J Med Genet A. 2024 Apr 29:e63637. doi: 10.1002/ajmg.a.63637. Online ahead of print.

Authors

Nadia Falah^{1

2}, Surekha Pendyal¹, Cina Sasannejad³, Allison Gibson⁴, Yu Lin Lee⁵, Marie McDonald¹, Dwight Koeberl^{1

6}

Affiliations

¹ Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
² Department of Medicine, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, USA.
³ Duke Department of Neurology, Duke University Medical Center, Durham, North Carolina, USA.
⁴ Division of Critical Care, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
⁵ Department of Medicine and Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
⁶ Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.

PMID: 38682838
DOI: 10.1002/ajmg.a.63637

Abstract

Significant progress has been achieved in enhancing early outcomes for individuals with maple syrup urine disease (MSUD), a rare metabolic disorder that leads to the accumulation of branched-chain amino acids leucine, isoleucine, and valine, where leucine is known as the primary neurotoxic metabolite. Newborn screening is helpful in early diagnosis and implementation of dietary treatment, thus reducing neurological deterioration and complications in young children. However, patients face the life-long challenge of maintaining metabolic control through adherence to a strict low-leucine diet to avoid long-term consequences of chronic hyperleucinemia, which include cognitive deficits, mood disorders, and movement disorders. This case report exemplifies the complex involvement of MSUD in adult survivors. Despite presenting early in life, the patient thrived until the onset of psychiatric symptoms. The subject of this case is a 25-year-old woman with MSUD, who remained in her usual state of health until presentation to the emergency department (ED) with psychosis and altered mental status. However, due to a lack of medical records and poor communication, there was a delay in considering MSUD as a primary cause of her psychiatric symptoms. Although a genetics consultation was later arranged and efforts were made to decrease plasma leucine to the therapeutic range, these interventions proved inadequate in halting her deterioration in health. Her condition worsened within 72 h, culminating in her untimely death. This case emphasizes the comorbidity of psychiatric involvement in MSUD, which contributes to metabolic decompensation that can lead to cerebral edema and death. This case also highlights the pressing need for enhanced strategies for the acute management and long-term care of MSUD patients with psychiatric involvement, particularly in scenarios where mental disturbance could lead to noncompliance.

Keywords: cerebral edema; maple syrup urine disease; metabolic decompensation; noncompliance; psychosis.

Publication types

Case Reports