AGC1 Deficiency and Cerebral Hypomyelination

Abstract

Wibom et al. (July 30 issue)¹ suggest that impaired function of mitochondrial aspartate–glutamate carrier isoform 1 (AGC1) leads to hypomyelination. However, the results of magnetic resonance imaging (MRI) suggest differently. In true hypomyelination, the supratentorial white matter is hyperintense on T₂-weighted MRI, and in young children cerebral atrophy is mild or absent ( Figure 1 ).² Early-onset, severe atrophy points to primary cortical degeneration.¹ The clinical features of the patient, including epilepsy and severe retardation, also suggest a cortical disease rather than a leukoencephalopathy. The reduced peak of N-acetyl aspartate found on spectroscopy indicates neuronal degeneration; this peak is considered to be normal or high in hypomyelination.³ Given the severe cerebral atrophy and less homogeneous hyperintensity of the white matter seen on T₂-weighted imaging, the MRI in this patient resembles that of patients with other early-onset neurodegenerative disorders, such as infantile neuronal ceroid lipofuscinosis ( Figure 1 ), in which impaired formation of myelin results from neuronal dysfunction and is not related to a defect in myelin or myelin metabolism. AGC1 deficiency should be considered a disorder of the gray matter, not a primary hypomyelinating disease.