Early initiation of ambroxol treatment diminishes neurological manifestations of type 3 Gaucher disease: A long-term outcome of two siblings
Autor: | David Ozretić, Katarina Bošnjak-Nađ, Tamara Žigman, Ivo Barić, Kousaku Ohno, Marija Zekušić, Ksenija Fumić, Danijela Petković Ramadža, Ana Škaričić, Ana Bogdanić, Gordana Mustać |
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Rok vydání: | 2021 |
Předmět: |
Male
Pediatrics medicine.medical_specialty Ambroxol Signs and symptoms Disease Early initiation 03 medical and health sciences 0302 clinical medicine 030225 pediatrics Secondary Prevention Medicine Humans Enzyme Replacement Therapy Younger sibling Sibling Child gaucher disease type 3 neuronopathic form ambroxol pharmacological chaperone Gaucher Disease business.industry Siblings Neurodegeneration Infant General Medicine Enzyme replacement therapy medicine.disease Child Preschool Pediatrics Perinatology and Child Health Glucosylceramidase Female Neurology (clinical) business 030217 neurology & neurosurgery medicine.drug |
Zdroj: | European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 32 |
ISSN: | 1532-2130 |
Popis: | Gaucher disease type 3 (GD3) is a severely debilitating disorder characterized by multisystemic manifestations and neurodegeneration. Enzyme replacement therapy alleviates visceral signs and symptoms but has no effect on neurological features. Ambroxol has been suggested as an enzyme enhancement agent. Some studies have confirmed its effectiveness in preventing the progression of neurological manifestations of neuronopathic Gaucher disease. In this study, we report two GD3 siblings in whom ambroxol combined with enzyme replacement therapy was initiated at different stages of the disease. We demonstrate the enzyme enhancement effect of ambroxol on L444P/H225Q ; D409H glucocerebrosidase activity through results of fibroblast studies and long-term clinical outcomes of the two patients. The sibling diagnosed at the age of four-and-a- half years with significant neurological involvement manifested relatively rapid improvement on ambroxol treatment, followed by stabilization of further course. The younger sibling, in whom the treatment was started at seven weeks, displayed attention deficit and low average cognitive functioning at the age of seven years, but did not manifest other neurological symptoms. The difference in neurological outcomes indicates that ambroxol delayed or even halted the evolution of neurological manifestations in the younger sibling. This observation suggests that early initiation of ambroxol treatment may arrest neurological involvement in some GD3 patients. |
Databáze: | OpenAIRE |
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