JIMD Reports, Volume 24

João Stein Kannebley, Laura Silveira-Moriyama, Laís Orrico Donnabella Bastos, Carlos Eduardo Steiner

We describe 12 subjects of ten unrelated families from the region of Campinas and the southern state of Minas Gerais, Brazil, who presented with juvenile (n = 4) and adult (n = 8) GM1 gangliosidosis. Data includes clinical history, physical examination, and ancillary exam findings. Six subjects presented initially with skeletal deformities, while the remaining six had neurological manifestations at onset. Over time, all exhibited a combination of osteoarticular and neurologic degeneration with varying degrees of severity. Corneal clouding, angiokeratomas, and inguinal hernia were seen in one individual each. Other features commonly described in lysosomal storage disorders were not found in this series, such as coarse faces, gingival hypertrophy, visceromegaly, and cherry red spot. All subjects presented with short stature, dysostosis multiplex, dysarthria, and impairment of activities of daily living, 10/12 had extrapyramidal signs, 8/12 had pyramidal signs, 8/12 had oculomotor abnormalities, 4/12 had behavioral alterations, and 2/12 had ataxia. None had seizures or Parkinsonism. All female subjects developed severe hip dysplasia and underwent arthroplasty due to chronic pain. A vertebral bone bar and os odontoideum, not previously described in this condition, were found in one patient each. There was no clear genotype-phenotype correlation regarding enzyme residual activity and clinical findings, since all subjects were compound heterozygous, but the p.T500A was the most frequent allele in eight families and was associated to Morquio B phenotype. Two sets of siblings allowed intrafamilial comparison revealing consistent features among the families. Interfamilial correlation among unrelated families presenting the same mutations was less consistent.