Juvenile metachromatic leukodystrophy in a boy with epilepsy.

M leukodystrophy (MLD) is an autosomal recessive disorder, caused by deficiency of arylsulfatase A (cerebroside sulfatase A, ASA), which results in accumulation of sulfatides, mainly in the brain and peripheral nerves. The estimated frequency of MLD from previous reports is 1 in 40,000 cases. The deficiency in ASA activity is caused by mutations in the ASA gene. The deficiency is systemic and affects other organs, in addition to the nervous system.1 Metachromatic leukodystrophy presents with progressive mental retardation, behavioral abnormalities, and recurrent seizures. We report a case of juvenile MLD, in a young boy, presenting with epilepsy, and mental subnormality. It is one of the rare metabolic disorders, occurring with epilepsy in this patient, diagnosed in the late stage of the illness. We present a 14-year-old Pakistani boy, of nonconsanguineous parents, of full term normal delivery, with normal early developmental milestones, studied up to the first preliminary class. At the age of 7, he developed declined higher mental function, with slowness in school performance. He developed recurrent abdominal pain, with loss of appetite. He lost weight and had generalized muscle wasting. At the age of 12, he developed recurrent generalized tonic clonic convulsions. Later, he developed generalized tiredness and weakness, with difficulty in walking and developed unsteadiness of gait. Clinical examination showed a generalized thin body mass, with skin and bony appearance, with gross muscles wasting. He had microcephaly with a head circumference of 51 cm, and jerky horizontal nystagmus. He had bilateral pyramidal signs with mild to moderate motor weakness of all 4 limbs. No organomegaly was seen. Laboratory results revealed pancytopenia and megaloblastic anemia, with normal serum vitamin B12, folate levels, and serum arylsulfatase A level of 39 units (normal range: 55-80). Serum very long chain fatty acid level, CSF study, and abdominal ultrasound were normal. Bone marrow biopsy revealed megaloblastic anemia, with no evidence of leukemia or infiltration. The EEG showed abnormal record due to slow and irregular basic activity, with sharp and slow epileptiform discharges, in the fronto-central areas bilaterally. Nerve conduction study showed predominantly demyelinating sensory motor polyneuropathy. Sural nerve biopsy: light microscopy showed focal myelin degeneration of the peripheral nerves and occasional cells, containing metachromatic granules. The electron microscopic study showed focal myelin degeneration of large myelinated fibers, with occasional cells containing intracytoplasmic lipid globules, as well as lamellar inclusions, and endoneurial fibrosis. These features are of lipid storage disorder, consistent with MLD. An MRI brain showed microcephaly and severe parenchymal loss, with diffuse confluent high signal, white matter changes in the frontal, occipital, and periventricular areas, suggestive of demyelination, consistent with MLD (Figure 1). The clinical picture, physical findings, laboratory results, and radiological appearances were consistent with the diagnosis of MLD. He was treated with anticonvulsants, general supportive care, and other symptomatic treatment. However, his neurological deficits and neuromuscular condition, slowly progressed to severe muscle wasting and he was unable to walk, and confined to a wheelchair in due course. The more specific therapy for MLD, bone marrow transplantation was considered, but due to advanced staging of the illness and his very poor general condition, we could not carryout the special treatment. Due to recurrent intercurrent infections, progressive liver failure and systemic infection, leading to septicemia, unfortunately, he succumbed to death 2 years after the diagnosis. In the presented case, the onset of symptoms was at the age of 7, therefore making it possible to classify this as the Juvenile type of MLD. We have described the clinical picture, characteristic radiological appearances, enzymatic deficiency, and the various clinical presentations of juvenile MLD. Mental deterioration is often the first symptom. It appears in boys or girls, around 16 years of age. Poor school performances and recurrent school failures are common. Neurological symptoms, ataxia, cognitive, or psychiatric features are misdiagnosed as multiple sclerosis or spinocerebellar heredo-ataxia. Pyramidal and cerebellar symptoms with altered speech will occur. Central and Clinical Notes