Treatment Adrenal replacement therapy prolongs life and occasionally effects a partial neurologic remission. A diet enriched with monounsaturated fatty acids and devoid of long-chain fatty acids has been said to slow the progress of the disease when administered before the age of 6 years. Bone marrow transplantation, to date performed in more than 50 children, has been the only treatment shown to stabilize the disease and reverse some of the MRI changes. However, gene therapy with transduced autologous CD34+ cells (done ex vivo with a lentiviral vector) that contain ABCD1 complementary DNA has prevented the emergence of symptoms if instituted early in the disease, as in a preliminary report by Eichler and colleagues.
This form of leukodystrophy was described in relation to the inherited metabolic disorders of late infancy and early childhood in an earlier section. We mention it here to emphasize that the disease may have its onset at almost any age. Juvenile forms may begin between 4 and 12 years of age and adult forms between the midteens and the seventh decade of life. The mutations of the aryl sulfatase gene giving rise to these various forms are described in the earlier section on metachromatic leukodystrophy (MLD). Some of the sporadic cases reported in the adult probably were examples of cerebral multiple sclerosis, but we have seen, as have others, cases of MLD appearing as late as middle adult life. In almost all cases, the clinical picture, like those described by Turpin and Baumann, was one of slowly evolving intellectual decline or behavioral abnormality, followed by spastic weakness, hyperreflexia, Babinski signs, and stiff, short-stepped gait, with or without a polyneuropathy. Without manifest neurologic signs, misdiagnosis of psychiatric disease is common. As the disease progresses over a period of 3 to 5 years there may be a loss of vision and speech, then of hearing, and finally a state of virtual decerebration.
In some of these cases it is impossible to distinguish the white matter disease from that of Pelizaeus-Merzbacher and of Cockayne, described in the preceding section.
This refers to a heterogeneous group of disorders, also called nonmetachromatic leukodystrophy, in which no enzyme defect or special staining characteristic of degenerated white matter has been identified. Furthermore, most of them have been sporadic, obscuring the nosology of the process. One type is associated with cerebellar ataxia and dementia; other adult cases have been described in which epilepsy was associated with a frontal lobe type of dementia. A surprising feature, such as in the cases of Letournel and colleagues, has been normal MRI, even with the more sensitive FLAIR sequences. With whole exome sequencing, it has been possible to identify mutations in over one-third of such cases as described, for example, by Vanderver and coworkers. Not unexpectedly, these comprise a heterogenous group of disorders, usually isolated to a single family and in which the mechanism of white matter destruction or dysmyelination is for the most part, obscure.