Metachromatic Leukodystrophy and Nonverbal Learning Disability: Neuropsychological and Neuroradiological Findings in Heterozygous Carriers

Abstract

Metachromatic leukodystrophy (MLD) is an autosomal recessive neurodegenerative disorder due to deficiency of the enzyme arylsulfatase A that leads to progressive, diffuse demyelination. The syndrome of nonverbal learning disability has been attributed to white matter abnormality and has been reported in children with this disorder and in some healthy family member carriers of gene. We examined the neuropsychologic profiles and MRIs of eight members of the family of a 7-year-old girl with this disease, all of whom were heterozygous carriers of the mutation and five of whom were also carriers of the MLD pseudodeficiency gene. All had low normal levels of arylsulfatase A, and seven of the eight had average or better profiles across all assessed neuropsychological domains. The patient's younger sister had a profile with features of the syndrome of nonverbal learning disability despite a normal MRI, whereas two members with minor white matter findings did not. This family does not provide evidence for the syndrome of nonverbal learning disability in heterozygous carriers of the gene for MLD, even when associated with the MLD pseudodeficiency gene.

Can psychiatric childhood disorders be due to inborn errors of metabolism?

“…Taking learning disorders into consideration, some reports are found showing a link between learning disorders and adrenoleukodystrophy [ 31 , 32 ] and MLD [ 33 ], which is associated with nonverbal learning disability. Gordon [ 34 ] reported about glucose transporter type 1 deficiency as a preventable cause of severe learning difficulties.…”