A clinically severe variant of β-mannosidosis, presenting with neonatal onset epilepsy with subsequent evolution of hydrocephalus

Abstract

β-Mannosidosis results from a functional deficiency of the lysosomal enzyme, β-mannosidase. While being a well recognised, naturally occurring disease in both goats and cattle, it is an extremely rare disorder in humans with the first cases only being recorded in 1986. Until now the severity of the human disease has not mirrored that of its bovine or caprine counterparts, whose presentation is typically in the neonatal period with both altered skull morphology and seizures. Human β-mannosidosis has previously appeared to be a more indolent disease, with its only consistent phenotypic feature being developmental delay of varying severity. We report a patient, homozygous for a private mutation, who presented in the immediate perinatal period with seizures and who subsequently developed communicating hydrocephalus at 2 years of age. These are two new phenotypic features for β-mannosidosis. The first being the neonatal onset of the seizures, for while seizures have been seen in 3 out of the previous 20 documented cases, they have never before manifested prior to 6 months of age. However, as in the previous documented cases, the seizures were difficult to control and were associated with severe developmental delay. The second unique feature about this case was the development of communicating hydrocephalus. We discuss the possible mechanisms of its development. In summary, β-mannosidosis must thus now be considered in the differential diagnosis of neonatal onset seizures, and the potential for the development of hydrocephalus should be monitored during subsequent clinical follow-up.