Neurocognitive Decline and Motor Regression in a 34-Year-Old Woman

Sumaira Nabi, MBBS; Zakir Jan, MBBS, FCPS Neurology; Muhammad Irshad, MBBS, FCPS Neurology


April 23, 2018


This patient's radiologic data and clinical picture were consistent with metachromatic leukodystrophy (MLD). Because the patient had already progressed to a bedridden, quadriparetic state, she was referred for rehabilitation, and the family was counseled about the guarded prognosis and probable course of the disease. They were also counseled for genetic testing. No curative treatment is available for MLD; therefore, only supportive treatment could be offered. She was given atypical antipsychotics for her agitated and restless behavior.

The leukodystrophies are a set of rare, progressive diseases that affect the growth or maintenance of white matter (ie, myelin).[1] Most leukodystrophies are genetic disorders and are inherited in a recessive, dominant, or X-linked manner, depending on the type of disease. However, some leukodystrophies appear to be sporadic rather than inherited.

Many leukodystrophies have adult-onset variants.[2] These include MLD, adrenoleukodystrophy, and Krabbe disease, in addition to many other rare varieties. MLD is one of the most serious and rare inherited demyelination disorders and eventually progresses to a bed-bound, quadriplegic state, with loss of speech and comprehension.[3] A lysosomal storage disease, it is transmitted as an autosomal recessive trait and is characterized by demyelination of the white matter in the central nervous system and peripheral nerves.[1,4]

MLD results from a mutation in the ARSA gene, which codes for a deficiency of the enzyme arylsulfatase A. More rarely, MLD results from a mutation in the PSAP gene, which codes for the activator protein saposin B. Arylsulfatase A converts sulfatide to cerebroside (a major component of myelin).[5] Thus, the deficiency of arylsulfatase A results in sulfatide accumulation in the lysosomes of the brain and peripheral nerves. Accumulation of sulfatide affects the oligodendrocytes and Schwann cells, causing progressive demyelination. The incidence of MLD is estimated to be 1 case per 40,000 births.[1]

MLD is clinically heterogeneous with respect to the age of onset, effects on the peripheral and central nervous systems, and disease progression. It can manifest in the late infantile period, early juvenile period, late juvenile period, or adulthood.[1,6,7] It usually has its onset between ages 1 and 4 years. It is characterized in this age group by progressive motor regression with gait difficulties, in association with neurocognitive decline and reduced output of speech. However, seizures are rare. A variable degree of neuropathy may be present. One third of the affected children have optic atrophy. The course of the disease is rapid and the outcome fatal, with a mean survival of 3-4 years.


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