{"id":"3a4aaa64-2e72-530b-ab85-488498f6439e","stable_key":"1b599eb7-b22a-5fda-bcf0-9d92b5ae1311:gb-losing-the-phosphatase-costs-the-cofactor","predicate":"enables","statement":"Hypophosphatasia is a rare inherited disorder of bone and mineral metabolism caused by loss-of-function mutations in the ALPL gene, characterized by defective bone and tooth mineralisation associated with low serum and bone alkaline phosphatase activity, severe forms may present with neurological problems such as seizures, hypotonia and irritability, and here an infantile hypophosphatasia patient presented with pyridoxine-responsive seizures and a novel homozygous mutation in the ALPL gene was detected, with a limited number of such patients in the literature.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"15b54731-0759-509d-8953-d2d81fd6fe5d","mechanism_event_label":"A child whose alkaline phosphatase does not work had seizures that only pyridoxine controlled.","subject":{"id":"3148c377-9b4c-56ca-bc36-081bf1905d57","slug":"alpl","display_name":"Tissue-nonspecific alkaline phosphatase ALPL / TNAP","entity_type_key":"protein"},"object":{"id":"ce25d23b-4ea3-5f9a-bc4e-cece359c777c","slug":"pyridoxine-responsive-seizures","display_name":"Pyridoxine-responsive seizures in infantile hypophosphatasia","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"15b54731-0759-509d-8953-d2d81fd6fe5d","stable_key":"1b599eb7-b22a-5fda-bcf0-9d92b5ae1311:gb-losing-the-phosphatase-costs-the-cofactor-event","event_type":"observed_intervention","label":"A child whose alkaline phosphatase does not work had seizures that only pyridoxine controlled.","description":"Hypophosphatasia is a rare inherited disorder of bone and mineral metabolism caused by loss-of-function mutations in the ALPL gene, characterized by defective bone and tooth mineralisation associated with low serum and bone alkaline phosphatase activity, severe forms may present with neurological problems such as seizures, hypotonia and irritability, and here an infantile hypophosphatasia patient presented with pyridoxine-responsive seizures and a novel homozygous mutation in the ALPL gene was detected, with a limited number of such patients in the literature.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6b656ff5-9532-5da4-8eea-8ca163a48649","slug":"pyridoxal-phosphate","display_name":"PLP","entity_type_key":"small_molecule"},"role":"undeliverable_cofactor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e68a88e0-23f1-516c-831c-9df49c7ed504","slug":"pyridoxine-dependent-seizures","display_name":"Pyridoxine-dependent seizures","entity_type_key":"cellular_process"},"role":"related_condition","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"3148c377-9b4c-56ca-bc36-081bf1905d57","slug":"alpl","display_name":"Tissue-nonspecific alkaline phosphatase ALPL / TNAP","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"ce25d23b-4ea3-5f9a-bc4e-cece359c777c","slug":"pyridoxine-responsive-seizures","display_name":"Pyridoxine-responsive seizures in infantile hypophosphatasia","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/gaba-research/27086862.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"cb18a717a009e567b4480c6826b39f15109745dbb646c752ad66376b6b107854\", \"start_char\": 0, \"end_char\": 1299, \"text_sha256\": \"cb18a717a009e567b4480c6826b39f15109745dbb646c752ad66376b6b107854\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Case report of an infant with a novel homozygous ALPL mutation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Loss-of-function ALPL mutation with pyridoxine-responsive seizures","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A single case report. 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It shows the association in one patient and cannot establish how often it occurs or the mechanism by which the cofactor becomes unavailable.\nexposure: Loss-of-function ALPL mutation with pyridoxine-responsive seizures\nevidence_span: {\"source_cache\": \"artifacts/gaba-research/27086862.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"cb18a717a009e567b4480c6826b39f15109745dbb646c752ad66376b6b107854\", \"start_char\": 0, \"end_char\": 1299, \"text_sha256\": \"cb18a717a009e567b4480c6826b39f15109745dbb646c752ad66376b6b107854\"}\n[gb-p27086862] Pyridoxine-Responsive Seizures in Infantile Hypophosphatasia and a Novel Homozygous Mutation in ALPL Gene. 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