1Serviço de Genética Médica, Área da Mulher, Criança e Adolescente, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
2Serviço de Neuropediatria, Área da Mulher, Criança e Adolescente, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
3Centro de Referência de Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
4Unidade de Rastreio Neonatal, Metabolismo e Genética, Instituto Nacional de Saúde Dr. Ricardo Jorge, Porto, Portugal
- Poster -15th International Symposium of Sociedade Portuguea de Doenças Metabólicas
- Coimbra, 14 a 16 março de 2019
Background: GM1 gangliosidosis (GM1) and mucopolysaccharidosis type IVB (MPS IVB) are caused by beta-galactosidase deficiency due to GLB1 mutations. GM1 is a neurodegenerative disorder characterized by the accumulation of GM1 ganglioside that can present with hepatosplenomegaly, cardiomyopathy, facial dysmorphism, and minor skeletal dysplasia. In contrast, patients with MPS IVB retain neurological functions, but develop evident generalized skeletal dysplasia, keratan sulfaturia and corneal clouding.
Case report: A 9-year-old girl was referred to our genetic clinic for developmental regression suggested by speech and gait disturbances. At our observation, she had slightly coarse face, short neck with low posterior hairline, hyperlordosis, short trunk, genu valgum and no hepatosplenomegaly. She had signs of moderated platyspondyly and epiphyseal dysplasia, normal cardiac and ophthalmologic examination, and normal cerebral MRI. A hypothesis of lysossomal storage disorder was presumed and collection of dried blood spots for FIND PROJECT were made. Enzymatic studies revealed a beta-galactosidase deficiency, compatible with both MPS IVB or GM1. Sanger sequencing of GLB1 gene revealed compound heterozygosity for two mutations: c.602G>A and c.1572_1577insG, previously reported in patients with both GM1 and MPS IVB. Further investigation showed normal urinary glycosaminoglycans and slight excretion of urinary gangliosides, concluding for GM1 diagnosis.
Conclusion: FIND PROJECT is a simple and useful tool available to the physicians to diagnose symptomatic MPS patients at pediatric age. The approach to differentiate beta-galactosidase deficiency from GM1 or MPS IVB must take into account genetic analysis, urinary glycosaminoglycans and oligossacharydes as well as a close discussion with clinical physicians.