Alpha-mannosidosis (AMS) is an autosomal recessive lysosomal storage disorder which results from a deficiency of lysosomal alpha-mannosidase [corrected] activity and displays a wide range of clinical phenotypes. Patients have traditionally been divided into type I, a more severe form that presents in infancy, and type II, a milder form that typically presents in later childhood. We describe three Hispanic males who presented in infancy with relatively mild forms of AMS. They were aged between 6 and 24 years at their last assessment. Homozygous mutations in the MAN2B1 gene were found in all three patients, one of which is a newly reported mutation. Two of the patients were brothers who were homozygous for the same MAN2B1 mutation. Despite being homozygous for the same mutation, the older brother had more severe developmental delay, hearing loss, and growth retardation. This report illustrates the difficulty in determining a strict genotype-phenotype correlation in AMS, and supports screening for oligosaccharides in children with neurodevelopmental delay with mild phenotypic signs and symptoms.