Skip to content

IEMbase 0561: ALPL-related hypophosphatasia

Scope

Field Value
IEMbase ID 561
Nosology 21.6.03.01
Gene ALPL
External IDs OMIM:241500; ORPHA:436
Generated mapping MAPPED; Hypophosphatasia.yaml
Candidate DisMech targets Hypophosphatasia.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents ALPL-related tissue-nonspecific alkaline phosphatase deficiency, with alternate labels congenital hypophosphatasia, phosphoethanolaminuria, and HOPS. The record lists autosomal dominant and autosomal recessive inheritance, idiopathic subtype, unknown treatability, and an asfotase alfa enzyme-replacement treatment row.

Biochemical rows include increased urinary phosphoethanolamine, increased plasma pyridoxal phosphate, very low plasma alkaline phosphatase, normal-high to high plasma calcium, and low-normal to low plasma phosphate. Clinical rows include dentine hypoplasia, premature dentition exfoliation, respiratory failure, taurodontism, and thin dentinal walls. Characteristic rows include seizures and skeletal hypomineralization.

DisMech phenotype coverage

Hypophosphatasia.yaml is the correct local target. The entry models ALPL loss of function, tissue-nonspecific alkaline phosphatase deficiency, reduced alkaline phosphatase and pyrophosphatase activity, accumulation of inorganic pyrophosphate, pyridoxal phosphate, and phosphoethanolamine, impaired hydroxyapatite formation, and decreased bone mineralization. It also covers dominant and recessive inheritance across severity levels and asfotase alfa enzyme replacement.

Concordance and completeness

Judgement: correct high-concordance mapping to Hypophosphatasia.yaml.

IEMbase and DisMech agree on ALPL identity, mixed dominant/recessive inheritance, low alkaline phosphatase, elevated PLP and PEA, mineralization failure, skeletal hypomineralization, dental involvement, seizures, and asfotase alfa treatment. DisMech is stronger for the pyrophosphate-mediated bone-mineralization mechanism and severity-spectrum framing.

IEMbase adds review prompts for calcium and phosphate directionality, respiratory failure, taurodontism, dentine hypoplasia, premature dentition exfoliation, and thin dentinal walls.

Curation actions

  • Keep this record mapped to Hypophosphatasia.yaml.
  • Consider source-checking IEMbase dental subfeatures, respiratory failure, calcium/phosphate rows, and seizure framing for possible local additions.
  • Keep asfotase alfa linked to pediatric-onset or severe disease context where evidence supports that scope.