A case of adult onset metachromatic leukodystrophy


METACHROMATIC LEUKODYSTROPHY (MLD) is an autosomal recessive disease caused by a mutation in the arylsulfatase A (ASA) gene. The possibility of MLD in middle-aged patients is seldom entertained because most cases of MLD are of late-infantile onset. We report a 59-year-old man with adult-onset MLD, which suggests that MLD should be considered in the differential diagnosis of presenile dementia.

The patient's developmental milestones were normal. At age 50, he began to have some difficulty at his job. When the patient first visited our hospital at age 52, he was polite and cooperative but deficient in concentration and attention. Wechsler Adult Intelligence Scale–Revised (WAIS–R) full-scale IQ was 61 (Verbal IQ 67, Performance IQ 63). Brain magnetic resonance imaging showed diffuse cerebral white matter involvement, most prominent in the frontal lobes, as well as diffuse cortical atrophy and thinning of the corpus callosum.

At age 53, he developed urinary incontinence, dressing apraxia, and personality changes including hypospontaneity, dysphoria, and bursts of aggression.

At age 54, he exhibited apathy, agraphia and bradykinesia. He had pes cavus and a broad-based gate. Neurological examination revealed snout reflex, palmomental reflex, and frontal ataxia, all of which suggest frontal lobe involvement. In the lower limbs, tendon reflexes were weak, and deep sensation was reduced. Conduction velocity of the median nerve was reduced to 21.1 m/sec. Disorientation to time and place, and severe impairment of attention and working memory were obvious. WAIS-R full-scale IQ was 47 (Verbal IQ 63, Performance IQ < 46). Electroencephalography showed a slow basic rhythm, with focal delta waves over the bilateral frontal and temporal regions. Single photon emission computed tomography with Tc-99m ethyl-cysteinate dimer revealed decreased regional blood flow in the bilateral frontal and temporal lobes. The cerebrospinal fluid had a protein concentration of 172 mg/dl. The level of leukocyte ASA activity was low at 10.7 nmol/mg protein/hr. Urinary sulfatides were not detected. A molecular genetic study showed a compound of two mutations in the ASA gene, the L289S and the T409I mutation.

At the time of writing the patient, aged 59, exhibits akinetic mutism with occasional epileptic seizures.

The bradykinesia, gait disturbance, and personality changes including blunted affect, apathy, and bursts of aggressiveness are consistent with features of subcortical dementia.1 These manifestations differ from those of cortical dementia such as Alzheimer's disease.

The onset of adult MLD generally occurs in the second or third decade of life.2 The case reported herein represents the latest onset of MLD in Japan, suggesting that as long as progressive dementia with white matter abnormality is present, the possibility of MLD should be considered, regardless of the patient's age.

Received 21 July 2008; accepted 27 August 2008.