Adult Forms of Metachromatic Leukodystrophy: Clinical and Biochemical Approach

Abstract

The clinical and biochemical characteristics of metachromatic leukodystrophy (MLD), true adult forms and late juvenile forms which are still living at adulthood, are reviewed as they both are observed in adult Neurology and Psychiatry departments. Mental deterioration is often the first symptom, evolving progressively; and dementia finally occurs. The latency before the appearance of neurological objective symptoms may be long and extend for several years. In many cases, the behavioral abnormalities are the first symptoms. Some of these forms have been diagnosed as schizophrenia. Very seldom, neurological symptoms, especially ataxia, occur without cognitive or psychiatric disturbances. Most of these cases have pyramidal and cerebellar symptoms, at diverse degrees. Seizures can also occur which in some cases can be early symptoms associated to mental deterioration. The association of central and peripheral neurological symptoms is very characteristic of MLD. The peripheral neuropathy is not generally clinically evidenced, but is rarely-missing electrophysiologically. Arylsulfatase A determination should be performed for diagnosis as a first step, and confirmed by the accumulation of sulfatide, either by quantitative determinations in urine or by the sulfatide loading test. It is as yet not clear why certain forms have a rather rapid evolution in 5 years, and others have a very protracted course during decades.

Leukoencephalopathies associated with inborn errors of metabolism in adults

“…Clinical onset can be as late as the seventh decade of life (Bosch and Hart 1978;Von Figura et al 2001). In adults, first symptoms are usually psychiatric, mimicking schizophrenia with delusion, hallucinations, disorganized behaviour and social dysfunction (Baumann et al 1991). The clinical picture is completed after several years or decades by cognitive deficits as well as motor signs (spastic paraparesis, cerebellar ataxia, mild demyelinating polyneuropathy).…”

Clinical Symptoms of Adult Metachromatic Leukodystrophy and Arylsulfatase A Pseudodeficiency

“…In 1991, the clinical signs and symptoms of 23 patients with MLD described in the literature were reviewed by Baumann et nl. 4 One patient from their review was not included in our analysis be cause he was already included as patient 2 in the pres ent study. Recently, two other patients with confirmed MLD have been described.…”

Adult-onset leukodystrophies

“…It gives rise to demyelination of CNS and of PNS. In the adult the circumstances of diagnosis are variable [2]. It is often a progressive mental deterioration.…”

“…Many of the sphingolipids are common to the CNS and to the peripheral nervous system (PNS). The metabolic abnormalities may involve the lysosome such as Krabbe disease and metachromatic leukodystrophy (MLD) or the peroxisome such as adrenoleukodystrophy (ALD) [2,32,44]. Many protein components of the oligodendrocyte and myelin have been identified in recent years, but not as yet linked to any leukodystrophy, except for Pelizaeus-Merzbacher disease (PMD).…”