Leukoencephalopathies associated with inborn errors of metabolism in adults

Abstract

The discovery of a leukoencephalopathy is a frequent situation in neurological practice and the diagnostic approach is often difficult given the numerous possible aetiologies, which include multiple acquired causes and genetic diseases including inborn errors of metabolism (IEMs). It is now clear that IEMs can have their clinical onset from early infancy until late adulthood. These diseases are particularly important to recognize because specific treatments often exist. In this review, illustrated by personal observations, we give an overview of late-onset leukoencephalopathies caused by IEMs.

Imaging of adult leukodystrophies

“…Very rarely, the X-ALD women present adrenal insufficiency or brain involvement. Brain MRI can be normal or be similar to that seen in adrenomyeloneuropathy 3,5,7 .…”

“…ALD mutation may occur in women and they sometimes manifest milder symptoms 5 . Adrenomyeloneuropathy is a slowy progressive disease that presents with adrenal insufficiency, distal axonopathy (predominantly affecting the corticospinal tracts and dorsal columns of spinal cord) and peripheral neuropathy 1,3 . The clinical presentation is usually spastic paraparesis.…”

“…Metachromatic leukodystrophy is an autosomal recessive lysosomal disease caused by a deficiency of the enzyme arylsulfatase A (ARSA) that leads to the accumulation of sulfatides in oligodendrocytes, Schwann cells and some neurons causing demyelination both in the central as well as in the peripheral nervous systems 3 . More than 100 mutations causing metachromatic leukodystrophy have been identified.…”

“…In adulthood the main clinical presentations are psychiatric problems (cognitive, behavioral problems and memory deficits) sometimes mimicking schizophrenia followed by motor signs, such as spastic paraparesis, cerebellar ataxia and mild polyneuropathy. The disease course is self-limiting 3,8 . MRI shows a bilateral periventricular leukoencephalopathy predominantly in the frontal regions, sparing the U-fibers in the initial phase of the disease.…”

“…MRI is a useful tool to evaluate new forms of leukodystrophies and to allow longitudinal studies of disease progression 2,3,4 . The aim of this review is to briefly describe the imaging characteristics of the most common adult leukodystrophies.…”