Clinical utility of brain MRS imaging of patients with adult-onset non-cirrhotic hyperammonemia

Andrew B Stergachis; Joel B Krier; Sai K Merugumala; Gerard T Berry; Alexander P Lin

doi:10.1016/j.ymgmr.2021.100742

Clinical utility of brain MRS imaging of patients with adult-onset non-cirrhotic hyperammonemia

Mol Genet Metab Rep. 2021 Mar 13:27:100742. doi: 10.1016/j.ymgmr.2021.100742. eCollection 2021 Jun.

Authors

Andrew B Stergachis^{1

2}, Joel B Krier³, Sai K Merugumala⁴, Gerard T Berry⁵, Alexander P Lin⁴

Affiliations

¹ Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.
² Brotman Baty Institute for Precision Medicine, Seattle, WA, USA.
³ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁴ Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

Adult-onset non-cirrhotic hyperammonemia (NCH) is a rare, but often fatal condition that can result in both reversible and irreversible neurological defects. Here we present five cases of adult-onset non-cirrhotic hyperammonemia wherein brain magnetic resonance spectroscopy (MRS) scans for cerebral glutamine (Gln) and myo-inositol (mI) levels helped guide clinical management. Specifically, we demonstrate that when combined with traditional brain magnetic resonance imaging (MRI) scans, cerebral Gln and mI MRS can help disentangle the reversible from irreversible neurological defects associated with hyperammonemic crisis. Specifically, we demonstrate that whereas an elevated brain MRS Gln level is associated with reversible neurological defects, markedly low mI levels are associated with a risk for irreversible neurological defects such as central pontine myelinolysis. Overall, our findings indicate the utility of brain MRS in guiding clinical care and prognosis in patients with adult-onset non-cirrhotic hyperammonemia.

Keywords: BG, Basal ganglia; Cerebral glutamine; Cerebral myo-inositol; Gln, Glutamine; Magnetic resonance spectroscopy; NAA, N-acetylaspartate; NAAG, N-acetylaspartylglutamate; NCH, Non-cirrhotic hyperammonemia; Non-cirrhotic hyperammonemia; PCG, Posterior cingulate gyrus; PWM, Parietal white matter; Urea cycle disorder; mI, Myo-inositol.

Abstract

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