Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Raimann, A; Haberler, C; Patsch, J; Ertl, DA; Sadeghi, K; Freilinger, M; Lang, S; Schmook, M; Plecko, B; Haeusler, G.
Lethal Encephalopathy in an Infant with Hypophosphatasia despite Enzyme Replacement Therapy.
Horm Res Paediatr. 2021; 94(9-10): 390-398.
Doi: 10.1159/000520341
(- Case Report)
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Plecko Barbara
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- Abstract:
- Hypophosphatasia (HPP) is an inborn error of metabolism caused by loss-of-function mutations in the biomineralization-associated alkaline phosphatase gene, encoding tissue-nonspecific alkaline phosphatase (TNSALP). Symptoms include skeletal hypomineralization and extra-skeletal manifestations such as pyridoxine (B6)-responsive seizures due to impaired cerebral B6 passage. Since the introduction of enzyme replacement therapy (ERT), skeletal manifestations and B6-responsive seizures were reported to improve significantly. Nevertheless, there is an increasing evidence of B6-independent neurological manifestation of HPP including HPP-associated encephalopathy. Here, we present for the first time the brain alterations of an infant with neonatal HPP who died of neurological complications at the age of 5 months despite early initiation of ERT. CSF analysis showed normal concentrations of biogenic amines reflecting sufficient intracellular B6 availability. Postmortem histopathology revealed severe, localized affection of the cerebral cortex including cortical lesions in layers 2 and 3 in direct proximity to TNSALP-expressing neurons and hippocampal sclerosis. Our findings confirm that TNSALP deficiency may lead to a severe encephalopathy. We hypothesize that HPP-associated encephalopathy resistant to currently available ERT may develop in addition and probably independently of typical B6-responsive seizures in some patients. Prospective, controlled studies with close neurological follow-up including brain imaging are needed to identify patients at risk for severe neurological symptoms despite ERT.
- Find related publications in this database (Keywords)
- Rare diseases
- Vitamin B6
- Alkaline phosphatase
- Asfotase alfa
- Bone
- Encephalopathy
- Enzyme replacement therapy
- Hypophosphatasia
- Pyridoxine