Clinical Findings and Natural History in Ten Unrelated Families with Juvenile and Adult GM1 Gangliosidosis

Abstract

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.

Competing interests: None declared

Synopsis

Juvenile and adult GM1 gangliosidosis

Compliance with Ethics Guidelines

Conflict of Interest Statement

João Stein Kannebley, Laís Orrico Donnabella Bastos, Laura Silveira-Moriyama, and Carlos Eduardo Steiner declare that they have no conflict of interest.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients or their guardians for being included in the study. This study was approved by the Research Ethics Committee FCM/Unicamp under protocol no. 236/2011.

Animal Rights

This study did not include laboratory animals.

Details of Author Contributions

João Stein Kannebley planned the work, revised patient’s records, performed clinical evaluation, and wrote the manuscript.

Laís Orrico Donnabella Bastos performed neurological examination and revised the manuscript.

Laura Silveira-Moriyama performed neurological examination and revised the manuscript.

Carlos Eduardo Steiner planned the work, performed clinical diagnosis, provided clinical care and follow-up of the patients, and revised the manuscript.