Juvenile progressive dystonia: A new phenotype of G_M2 Gangliosidosis

Abstract

A 10-year-old boy developed progressive dystonia and dementia. His symptoms had begun at age 2 1/2 years, and he had been unable to walk by 8 years. At age 10 he was severely dystonic, unable to use his hands to feed himself, and almost anarthric . He had dysphagia and urinary incontinence, and functioned at a 4-year-old level of mental development. The mean percentages of beta-hexosaminidase A measured in serum, leukocytes, and fibroblasts by the heat denaturation method, each on three separate assays, were 5.9, 9.8, and 13.0%, respectively. These values are higher than in Tay-Sachs disease but are similar to levels seen in late-onset or adult cases of GM2 gangliosidosis. This patient appears to represent a new phenotype of juvenile GM2 gangliosidosis having dystonia as the dominant symptom.

Progressive dystonia symptomatic of juvenile GM2 gangliosidosis

“…No pharmacological treatment is mentioned in the case described by Meek et al (27). The improvement obtained in our patient treated with anticholinergic drug suggests the efficacy, not previously reported, of this therapy in the dystonia symptomatic of metabolic disorders.…”

Miglustat in late-onset Tay-Sachs disease: a 12-month, randomized, controlled clinical study with 24 months of extended treatment

“…Sandhoff disease is caused by a deficiency of ␤-hexosaminidase A and B and occurs once in every 384,000 live births. 1,2 There are three clinical variants of TSD based on age of onset: infantile acute onset (type I), 3 subacute (2-18 years, type II), 4,5 and late-onset (adulthood, type III) (LOTS). 6,7 In the subacute form, an earlier age at onset of the disease is indicative of a more severe disease course.…”

“…These latter subtypes differ primarily in their neurologic features and course of disease. 1,10 The subacute form is characterized by progressive spasticity with seizures and dementia, leading to a vegetative state by late childhood or mid-teens, 5,9 whereas patients with the chronic form tend to suffer mild cognitive decline and psychiatric complaints and may live a normal lifespan. 11,12 Often chronically affected patients become wheelchair bound.…”

A Chronic GM(2) Gangliosidosis Variant with a HEXA Splicing Defect: Quantitation of HEXA mRNAs in Normal and Mutant Fibroblasts

“…We also speculate that the pyrimidine tract in intron 7 may contribute to the inflexibility of lariat formation in this intron, preventing either formation of a lariat structure smaller than that Heteroallelism is often associated with a wide varia tion in phenotype. The GM2 gangliosidoses, many of which are caused by HEXA mutations, include infantile-, juvenile-and adult-onset forms of TSD (with multiple variant phenotypes) [35][36][37][38][39][40][41][42], The biochemical basis for these phenotypic differences is not known, but available evidence supports the hypothesis that the severity of the disorder is inversely related to the amount of residual Hex A activity associated with the patient's genotype. Such correlations are not easily established for the less severe variants, especially when variable phenotypes are ob served in patients with the same genotype.…”