In an Ohio Amish isolate, Cross and McKusick (1967) found 20 cases of a recessively inherited form of presenile dementia, which they termed Mast syndrome. Onset in the late teens or twenties and slow progression with development of ... In an Ohio Amish isolate, Cross and McKusick (1967) found 20 cases of a recessively inherited form of presenile dementia, which they termed Mast syndrome. Onset in the late teens or twenties and slow progression with development of spastic paraparesis and basal ganglion manifestations were features. Simpson et al. (2003) investigated 29 family members from the extended Amish pedigree originally studied by Cross and McKusick (1967), of whom 14 were affected with Mast syndrome. The condition was clearly progressive in all cases, leading to akinetic mutism in the most severely affected subjects. Developmental delays, including motor difficulties with mild incoordination and awkward running, were sometimes noted in childhood. The patients were perceived as relatively normal in teenage years and early adulthood, and several were married, had children, obtained driving licenses, and held jobs. In some, decline in walking and mental function was evident by the early twenties, whereas in others there was no clear history of a decline before their late thirties or early forties. Examination revealed pyramidal signs in all subjects, with hypertonicity, brisk reflexes, and extensor plantars; these were more severe in the lower than in the upper limbs. MRI showed thin corpus callosum and white matter abnormalities.
By linkage analysis in the Amish pedigree with Mast syndrome originally described by Cross and McKusick (1967), Simpson et al. (2003) mapped the Mast syndrome locus to a small interval of 15q22.31 encompassing 3 genes. Sequence analysis of ... By linkage analysis in the Amish pedigree with Mast syndrome originally described by Cross and McKusick (1967), Simpson et al. (2003) mapped the Mast syndrome locus to a small interval of 15q22.31 encompassing 3 genes. Sequence analysis of the 3 transcripts revealed that all 14 affected patients were homozygous for a 1-bp insertion in the ACP33 gene (601insA; 608181.0001). The protein, which had been shown to localize to intracellular endosomal/trans-Golgi transportation vesicles and was thought to function in protein transport and sorting, was designated maspardin (Mast syndrome, spastic paraplegia, autosomal recessive, with dementia).