Early infantile form of Krabbe disease with optic hypertrophy: serial MR examinations and autopsy correlation.

Summary: The development of white matter lesions in a case of autopsy-proved early infantile form of Krabbe disease was mon­ itored by serial MR examinations. Hypertrophy of the optic nerves was present late in the course of the patient's disease and is a remarkable feature in this case. Krabbe disease (globoid cell leukodystrophy or galctosylceramide lipoidosis) is an auto­ somal recessively inherited metabolic disease involving a deficiency of galactocerebroside J3-galactosidase, an enzyme that degrades ce­ rebroside to galactose and ceramide. Cerebro­ side then accumulates in the brain and elicits the typical "globoid cell response" (1). Be­ cause cerebroside is practically absent in im­ mature brains, the lack of galactocerebroside J3-galactosidase is of little consequence in very early infancy. As soon as myelination begins and myelin undergoes its normal turn­ over, cerebroside from catabolized myelin cannot be degraded and produces its fatal ef­ fect (2). At autopsy, the brain is reduced in size, with marked loss of white matter, whereas the cortex is relatively normal. There is diffuse demyelination of the cerebral and cerebellar white matter; U fibers are usually normal. Peripheral nerves are also affected and feature markedly reduced conduction ve­ locity. The cerebrospinal fluid contains abnor­ mally high protein levels; the electroencepha­ logram reveals slow activity and high voltage (2). The clinical course of the disease can be divided into three clinical stages according to Hagberg (3), beginning with a period of hy­ perirritability and finally resulting in a vegeta­ tive or burnt-out stage. Received May 17, 1993; accepted after revision September 14. Magnetic resonance (MR) provides an unique opportunity to see abnormal myelination ( 4), but reports on MR findings in early infantile form of Krabbe disease are rare (5). This case dem­ onstrates the MR appearance of early brain ab­ normalities and their temporal development, which might be helpful for diagnosing the dis­ ease early. We also describe our observation of optic hypertrophy as opposed to atrophy else­ where in the brain.