Elsevier

Brain and Development

Volume 19, Issue 7, November 1997, Pages 488-491
Brain and Development

Case report
Early infantile Krabbe disease: deceptively normal magnetic resonance imaging and serial neurophysiological studies

https://doi.org/10.1016/S0387-7604(97)00049-1Get rights and content

Abstract

Early infantile Krabbe disease is a progressive neurodegenerative disease caused by deficiency of lysosomal enzyme galactocerebroside β-galactosidase, with onset before the age of 6 months. We present serial clinical, radiological and neurophysiological findings of a patient with early infantile Krabbe disease, presenting at the third day of life with hypotonia, macrocephaly and neonatal seizures. The patient had a deceptively normal initial magnetic resonance imaging examination at the age of 3 months, with progression of the white matter disease over the following 9 months, showing a clinical picture of profound hypotonia with pyramidal and pseudobulbar signs, as well as mild optic atrophy. Assay of galactocerebroside β-galactosidase activity in leukocyte culture disclosed a marked deficiency of the enzyme (0.00 nmol/mg protein per h with normal values >0.7 nmol/mg protein per h), thus confirming the diagnosis of Krabbe disease. Nerve conduction velocity and evoked potential studies, as well as the electroencephalogram, were abnormal at the age of 6 months, while serial neurophysiological studies at the age of 12 and 18 months demonstrated the progressive nature of the disease.

Introduction

Globoid cell leukodystrophy (GLD; Krabbe disease), is a progressive neurodegenerative disease caused by deficient activity of galactosylceramidase (galactocerebroside β-galactosidase) and transmitted by autosomal recessive inheritance [1]. Neuroimaging studies, delay in nerve conduction velocities and elevated cerebrospinal fluid protein are suggestive of extensive myelin breakdown. An infantile form with onset before 6 months, a late infantile form with onset between 6 and 36 months, a juvenile form with onset between 3 and 7 years, and an adult one with onset after 7 years have been recognized according to differences in the age of onset and in the clinical manifestations 1, 2. Usually, patients with GLD manifest stagnation in psychomotor development and irritability between 4 and 6 months of age, while spasticity and peripheral neuropathy develop subsequently [1]. However, early infantile cases with onset immediately after birth are on record [1].

We report serial clinical, magnetic resonance imaging (MRI) and neurophysiological findings of a Greek patient with early onset GLD, who had a deceptively normal initial MRI examination.

Section snippets

Case report

The patient was a female born to healthy, non-consanguineous parents without a familial history of neurodegenerative disorders, delivered at term after cesarean section. At the third day of life, she was admitted to the hospital because of pronounced irritability and myoclonic jerks of the right arm (and occasionally of the right leg). Head circumference was above the 97th percentile, while the neurological examination demonstrated decreased muscle tone, brisk deep tendon reflexes and

Neuroradiological and neurophysiological studies

Cranial computed tomography (CT) at the third day disclosed no abnormality, while an electroencephalogram (EEG) showed generalised slow wave activity, predominately over the left parieto-occipital region.

A repeated EEG performed at 3 months of age, prior to antiepileptic drugs withdrawal, revealed mild generalised slowing with no paroxysmal or focal abnormalities, while magnetic resonance imaging (MRI) of the brain at the same age demonstrated normal findings, showing normal myelination of the

Discussion

Although there are numerous case descriptions of MRI findings in infantile GLD [1], only occasionally are serial MRI findings documented in early infantile 4, 5, 6or late infantile forms [7]. Finelli et al. [6], reported a patient with early infantile Krabbe disease who had a deceptively normal initial MRI examination. However, their patient had already an abnormal CT appearance prior to the MRI, with hyperdensities of the thalami, thus suggesting the disorder, since early CT changes in early

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