Hypophosphatasia

Summary

Hypophosphatasia (MONDO:0018570) is a disease (an umbrella term covering 8 Mondo subtypes) caused by ALPL (GenCC Definitive), with 2 cohort genes and 43 clinical trials. Top therapeutic interventions include asfotase alfa, bortezomib, and folic acid.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: ALPL (GenCC Definitive)
• Umbrella term: 8 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 691
• Phenotypes (HPO): 20
• Clinical trials: 43

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000	0.0208	China	Validated

Signs & symptoms

Clinical features (HPO)

20 HPO clinical features (Orphanet curated; top 20 by frequency):

HPO ID	Term	Frequency
HP:0000164	Abnormality of the dentition	Very frequent (80-99%)
HP:0000239	Large fontanelles	Very frequent (80-99%)
HP:0000772	Abnormal rib morphology	Very frequent (80-99%)
HP:0000774	Narrow chest	Very frequent (80-99%)
HP:0000944	Abnormal metaphysis morphology	Very frequent (80-99%)
HP:0001024	Skin dimple over apex of long bone angulation	Very frequent (80-99%)
HP:0001363	Craniosynostosis	Very frequent (80-99%)
HP:0001531	Failure to thrive in infancy	Very frequent (80-99%)
HP:0002097	Emphysema	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0006487	Bowing of the long bones	Very frequent (80-99%)
HP:0008872	Feeding difficulties in infancy	Very frequent (80-99%)
HP:0010781	Skin dimple	Very frequent (80-99%)
HP:0000737	Irritability	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0002093	Respiratory insufficiency	Frequent (30-79%)
HP:0002757	Recurrent fractures	Frequent (30-79%)
HP:0003072	Hypercalcemia	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hypophosphatasia
Mondo ID	MONDO:0018570
MeSH	D007014
Orphanet	436
DOID	DOID:14213
ICD-11	422012968
NCIT	C26798
SNOMED CT	360792001
UMLS	C0020630
MedGen	43799
GARD	0006734
MedDRA	10049933
Is cancer (heuristic)	no

Also known as: childhood hypophosphatasia · deficiency of alkaline phosphatase (disorder) [ambiguous] · HPP · hypophospatasia, childhood · hypophosphatasia mild · phosphoethanol-aminuria · phosphoethanolaminuria · Rathburn disease

Data availability: 691 ClinVar variants · 3 GenCC gene-disease records · 32 cell lines.

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › hypophosphatasia

Related subtypes (56): Neu-Laxova syndrome, inborn mitochondrial metabolism disorder, Ehlers-Danlos syndrome, spondylodysplastic type, MGAT2-congenital disorder of glycosylation, ALDH18A1-related de Barsy syndrome, classic homocystinuria, Larsen-like syndrome, B3GAT3 type, Nijmegen breakage syndrome, Peters plus syndrome, Wiedemann-Rautenstrauch syndrome, 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency, SHORT syndrome, mucosulfatidosis, CHIME syndrome, creatine transporter deficiency, multiple congenital anomalies-hypotonia-seizures syndrome 2, SLC35A2-congenital disorder of glycosylation, SSR4-congenital disorder of glycosylation, Fabry disease, occipital horn syndrome, Ehlers-Danlos syndrome, musculocontractural type, temtamy preaxial brachydactyly syndrome, B4GALT1-congenital disorder of glycosylation, AICA-ribosiduria, COG7-congenital disorder of glycosylation, permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome, Al-Gazali syndrome, COG1-congenital disorder of glycosylation, RFT1-congenital disorder of glycosylation, Nijmegen breakage syndrome-like disorder, multiple congenital anomalies-hypotonia-seizures syndrome 1, multiple congenital anomalies-hypotonia-seizures syndrome 3, autism spectrum disorder - epilepsy - arthrogryposis syndrome, cutis laxa, autosomal dominant 3, SLC39A8-CDG, transketolase deficiency, mucopolysaccharidosis-plus syndrome, Cockayne syndrome, pontocerebellar hypoplasia type 1, mandibuloacral dysplasia, hyperphosphatasia-intellectual disability syndrome, arthrogryposis-renal dysfunction-cholestasis syndrome, CADDS, XYLT1-congenital disorder of glycosylation, sterol biosynthesis disorder, mucolipidosis, mucopolysaccharidosis, oligosaccharidosis, encephalopathy due to sulfite oxidase deficiency, Fanconi anemia, autosomal recessive cutis laxa type 2, Zellweger spectrum disorders, pseudohypoparathyroidism, developmental and epileptic encephalopathy, 77, glycosylphosphatidylinositol biosynthesis defect 15, progressive hypotonia-intellectual disability-facial dysmorphism syndrome due to FYVE-defective RBSN

Subtypes (8): odontohypophosphatasia, ALPL-related autosomal dominant hypophosphatasia, ALPL-related autosomal recessive hypophosphatasia, moderate hypophosphatasia, prenatal benign hypophosphatasia, adult hypophosphatasia, childhood hypophosphatasia, infantile hypophosphatasia

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

131 pathogenic/likely pathogenic, 121 likely pathogenic, 101 uncertain significance, 98 pathogenic, 94 conflicting classifications of pathogenicity, 25 benign, 21 likely benign, 9 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1003680	NM_000478.6(ALPL):c.1022A>G (p.His341Arg)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1020192	NM_000478.6(ALPL):c.1228T>C (p.Phe410Leu)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1030812	NM_000478.6(ALPL):c.1328C>T (p.Ala443Val)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1047062	NM_000478.6(ALPL):c.655A>G (p.Met219Val)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067343	NM_000478.6(ALPL):c.508A>G (p.Asn170Asp)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070177	NM_000478.6(ALPL):c.212G>A (p.Arg71His)	ALPL	Pathogenic	criteria provided, multiple submitters, no conflicts
1070178	NM_000478.6(ALPL):c.223G>A (p.Gly75Ser)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072423	NM_000478.6(ALPL):c.1240C>A (p.Leu414Met)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073912	NM_000478.6(ALPL):c.558G>A (p.Trp186Ter)	ALPL	Pathogenic	criteria provided, multiple submitters, no conflicts
1074126	NM_000478.6(ALPL):c.976G>C (p.Gly326Arg)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075198	NM_000478.6(ALPL):c.412del (p.Arg138fs)	ALPL	Pathogenic	criteria provided, multiple submitters, no conflicts
1076060	NM_000478.6(ALPL):c.203C>T (p.Thr68Met)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076087	NM_000478.6(ALPL):c.303C>A (p.Tyr101Ter)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076159	NM_000478.6(ALPL):c.484G>A (p.Gly162Ser)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076160	NM_000478.6(ALPL):c.532T>C (p.Tyr178His)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076161	NM_000478.6(ALPL):c.659G>C (p.Gly220Ala)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076697	NM_000478.6(ALPL):c.182-2A>G	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1224321	NM_000478.6(ALPL):c.1166C>A (p.Thr389Asn)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1224381	NM_000478.6(ALPL):c.657G>T (p.Met219Ile)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1300140	NM_000478.6(ALPL):c.1427A>C (p.Glu476Ala)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323883	NM_000478.6(ALPL):c.874C>A (p.Pro292Thr)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1327508	NM_000478.6(ALPL):c.1479C>A (p.Asn493Lys)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1334790	NM_000478.6(ALPL):c.69_74del	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1334794	NM_000478.6(ALPL):c.361G>A (p.Val121Met)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1334796	NM_000478.6(ALPL):c.214A>G (p.Ile72Val)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1339258	NM_000478.6(ALPL):c.247G>T (p.Glu83Ter)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1355608	NM_000478.6(ALPL):c.480del (p.Val161fs)	ALPL	Pathogenic	criteria provided, multiple submitters, no conflicts
13662	NM_000478.6(ALPL):c.535G>A (p.Ala179Thr)	ALPL	Pathogenic	criteria provided, multiple submitters, no conflicts
13663	NM_000478.6(ALPL):c.211C>T (p.Arg71Cys)	ALPL	Pathogenic	criteria provided, multiple submitters, no conflicts
13664	NM_000478.6(ALPL):c.881A>C (p.Asp294Ala)	ALPL	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 11 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ALPL	Definitive	Autosomal recessive	childhood hypophosphatasia	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ALPL	Orphanet:247623	Perinatal lethal hypophosphatasia
ALPL	Orphanet:247638	Prenatal benign hypophosphatasia
ALPL	Orphanet:247651	Infantile hypophosphatasia
ALPL	Orphanet:247667	Childhood-onset hypophosphatasia
ALPL	Orphanet:247676	Adult hypophosphatasia
ALPL	Orphanet:247685	Odontohypophosphatasia
OCA2	Orphanet:177901	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 1
OCA2	Orphanet:177904	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 2
OCA2	Orphanet:79432	Oculocutaneous albinism type 2
OCA2	Orphanet:98754	Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15
OCA2	Orphanet:98794	Angelman syndrome due to maternal 15q11q13 deletion

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ALPL	HGNC:438	ENSG00000162551	P05186	Alkaline phosphatase, tissue-nonspecific isozyme	gencc,clinvar
OCA2	HGNC:8101	ENSG00000104044	Q04671	P protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ALPL	Alkaline phosphatase, tissue-nonspecific isozyme	Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis.
OCA2	P protein	Contributes to a melanosome-specific anion (chloride) current that modulates melanosomal pH for optimal tyrosinase activity required for melanogenesis and the melanosome maturation.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	1	55.8×	0.024
Phosphatase	1	42.0×	0.024

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ALPL	Phosphatase	yes	3.1.3.1	Alkaline_phosphatase, Alkaline_phosphatase_core_sf, Alkaline_phosphatase_AS
OCA2	Ion channel	yes		Cit_transptr-like_dom, Diverse_Ion_Transporter

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left adrenal gland cortex	1
right adrenal gland	1
right adrenal gland cortex	1
choroid plexus epithelium	1
pigmented layer of retina	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ALPL	200	broad	marker	right adrenal gland, right adrenal gland cortex, left adrenal gland cortex
OCA2	192	tissue_specific	marker	pigmented layer of retina, choroid plexus epithelium, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALPL	2,146
OCA2	2,132

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ALPL	P05186	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
OCA2	Q04671	73.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Melanin biosynthesis	1	1142.0×	0.002	OCA2
Post-translational modification: synthesis of GPI-anchored proteins	1	84.0×	0.012	ALPL

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
pyridoxal 5’-phosphate metabolic process	1	8426.0×	0.002	ALPL
response to vitamin B6	1	4213.0×	0.002	ALPL
futile creatine cycle	1	4213.0×	0.002	ALPL
melanin biosynthetic process from tyrosine	1	2106.5×	0.002	OCA2
response to macrophage colony-stimulating factor	1	2106.5×	0.002	ALPL
inhibition of non-skeletal tissue mineralization	1	2106.5×	0.002	ALPL
developmental process involved in reproduction	1	1685.2×	0.002	ALPL
lysosomal lumen pH elevation	1	1685.2×	0.002	OCA2
cementum mineralization	1	1203.7×	0.002	ALPL
response to sodium phosphate	1	842.6×	0.003	ALPL
melanin biosynthetic process	1	648.1×	0.004	OCA2
phosphate ion homeostasis	1	526.6×	0.004	ALPL
cellular homeostasis	1	401.2×	0.004	ALPL
melanocyte differentiation	1	401.2×	0.004	OCA2
response to vitamin D	1	401.2×	0.004	ALPL
response to antibiotic	1	351.1×	0.005	ALPL
endochondral ossification	1	271.8×	0.006	ALPL
calcium ion homeostasis	1	221.7×	0.007	ALPL
response to glucocorticoid	1	162.0×	0.009	ALPL
bone mineralization	1	135.9×	0.010	ALPL
response to insulin	1	115.4×	0.011	ALPL
positive regulation of cold-induced thermogenesis	1	81.8×	0.015	ALPL
spermatid development	1	72.6×	0.016	OCA2
skeletal system development	1	62.9×	0.017	ALPL
response to lipopolysaccharide	1	62.4×	0.017	ALPL
osteoblast differentiation	1	60.6×	0.017	ALPL
cell population proliferation	1	51.4×	0.019	OCA2

Therapeutics

Drugs indicated or in trials for this disease

1 approved drug — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Status
Asfotase Alfa	Approved (phase 4)

1 drug in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Setrusumab	Phase 2

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ALPL	SULCONAZOLE NITRATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ALPL	7	4
OCA2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SULCONAZOLE NITRATE	4	ALPL
THEOPHYLLINE	4	ALPL
LEVAMISOLE	4	ALPL
MICONAZOLE NITRATE	4	ALPL
LEVAMISOLE HYDROCHLORIDE	4	ALPL
ISOQUERCETIN	2	ALPL
(-)-EPICATECHIN	2	ALPL

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ALPL	58	Binding:50, Functional:4, ADMET:3, Toxicity:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALPL	3.1.3.1	alkaline phosphatase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

7 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
SULCONAZOLE NITRATE	4	ALPL
THEOPHYLLINE	4	ALPL
LEVAMISOLE	4	ALPL
MICONAZOLE NITRATE	4	ALPL
LEVAMISOLE HYDROCHLORIDE	4	ALPL
ISOQUERCETIN	2	ALPL
(-)-EPICATECHIN	2	ALPL

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ALPL
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	OCA2
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
OCA2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 43.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	23
PHASE2	8
PHASE4	3
PHASE3	3
PHASE1/PHASE2	3
PHASE1	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02531867	PHASE4	COMPLETED	Post-approval Clinical Study of Asfotase Alfa Treatment for Patients With Hypophosphatasia (HPP) in Japan
NCT04189315	PHASE4	WITHDRAWN	Relieving Burden of Hypophosphatasia in Adults With Functional Impairment Due to Chronic Disease
NCT06015750	PHASE4	WITHDRAWN	Mitigate Immune-Mediated Loss of Therapeutic Response to Asfotase Alfa (STRENSIQ®) for Hypophosphatasia
NCT06079281	PHASE3	ACTIVE_NOT_RECRUITING	Phase 3 Study of ALXN1850 Versus Placebo in Adolescent and Adult Participants With HPP Who Have Not Previously Been Treated With Asfotase Alfa
NCT06079359	PHASE3	ACTIVE_NOT_RECRUITING	Phase 3 Study of ALXN1850 in Treatment-Naïve Pediatric Participants With HPP
NCT06079372	PHASE3	ACTIVE_NOT_RECRUITING	Phase 3 Study of ALXN1850 in Pediatric Participants With HPP Previously Treated With Asfotase Alfa
NCT01176266	PHASE2/PHASE3	COMPLETED	Open-Label Study of Asfotase Alfa in Infants and Children ≤ 5 Years of Age With Hypophosphatasia (HPP)
NCT07179640	PHASE1/PHASE2	RECRUITING	A Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALE1 in Healthy Adults and Adults With Hypophosphatasia in Order to Identify Suitable Doses of ALE1
NCT00744042	PHASE1/PHASE2	COMPLETED	Safety and Efficacy Study of Asfotase Alfa in Severely Affected Infants With Hypophosphatasia (HPP)
NCT00894075	PHASE2	WITHDRAWN	Safety and Efficacy Study of ENB-0040 in Juvenile Patients With Hypophosphatasia (HPP)
NCT00952484	PHASE2	COMPLETED	Safety and Efficacy of Asfotase Alfa in Juvenile Patients With Hypophosphatasia (HPP)
NCT01163149	PHASE2	COMPLETED	Safety and Efficacy Study of Asfotase Alfa in Adolescents and Adults With Hypophosphatasia (HPP)
NCT01203826	PHASE2	COMPLETED	Extension Study of Protocol ENB-006-09 - Study of Asfotase Alfa in Children With Hypophosphatasia (HPP)
NCT01205152	PHASE2	COMPLETED	Extension Study of Protocol ENB-002-08 - Study of Asfotase Alfa in Infants and Young Children With Hypophosphatasia (HPP)
NCT01406977	PHASE2	COMPLETED	Dose Escalation Study to Evaluate the Safety and Tolerability of Multiple Infusions of BPS804 in Adults With Hypophosphatasia (HPP)
NCT02456038	PHASE2	COMPLETED	Safety and Efficacy of Asfotase Alfa in Patients With Hypophosphatasia (HPP)
NCT02797821	PHASE2	COMPLETED	Pharmacokinetic and Dose Response Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia (HPP)
NCT05890794	PHASE1/PHASE2	COMPLETED	Pilot Trial of Single Dose Ilofotase Alfa in Hypophosphatasia
NCT00739505	PHASE1	COMPLETED	Safety Study of Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein Asfotase Alfa in Adults With Hypophosphatasia (HPP)
NCT04980248	PHASE1	COMPLETED	Study of ALXN1850 in Participants With Hypophosphatasia (HPP)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02237625	Not specified	RECRUITING	Natural History Study of Patients With Hypophosphatasia (HPP)
NCT02306720	Not specified	ENROLLING_BY_INVITATION	Registry of Patients With Hypophosphatasia
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT05234567	Not specified	RECRUITING	A Prospective Sub-Study of the Global Hypophosphatasia Registry
NCT05596539	Not specified	RECRUITING	Prospective, Longitudinal, Observational Registry of Adult Patients With Hypophosphatasia (REG-HYPO)
NCT06574282	Not specified	RECRUITING	Characteristics of Hypophosphatasia in Adult Patients in Rheumatology and Their Value in Developing an Algorithm to HPP-diagnosis - the COHIR Multi-center Study
NCT07390240	Not specified	RECRUITING	The Effect of Monoallelic Variants in the ALPL Gene on the Natural Course of Hypophosphatasia in Russia
NCT01419028	Not specified	COMPLETED	A Retrospective Study of the Natural History of Patients With Severe Perinatal and Infantile Hypophosphatasia (HPP)
NCT02104219	Not specified	COMPLETED	Retrospective, Non-interventional Natural History of Patients With Juvenile-onset Hypophosphatasia (HPP)
NCT02235493	Not specified	COMPLETED	Non-interventional Substudy of ALX-HPP-502 to Assess Natural History of Patients With Juvenile-onset HPP Who Served as Historical Controls in ENB-006-09
NCT02291497	Not specified	COMPLETED	Burden of Disease in Hypophosphatasia (HPP)
NCT02496689	Not specified	APPROVED_FOR_MARKETING	Expanded Access Program for Asfotase Alfa Treatment for Patients With Infantile- or Juvenile-onset Hypophosphatasia (HPP)
NCT02751801	Not specified	COMPLETED	Health Burden of Hypophosphatasia
NCT02796885	Not specified	COMPLETED	Characterisation of Adult-Onset Hypophosphatasia
NCT03418389	Not specified	COMPLETED	Evaluate and Monitor Physical Performance of Adults Treated With Asfotase Alfa for Hypophosphatasia
NCT04018287	Not specified	UNKNOWN	Circulating miRNAs and Bone Microstructure in Adults With Hypophosphatasia
NCT04181164	Not specified	UNKNOWN	Evaluation of Bone Architecture and Bone Strength in Adults With Hypophosphatasia (HPP)
NCT04195763	Not specified	COMPLETED	Patient Reported Outcomes in Adults With Pediatric-onset Hypophosphatasia Treated With Strensiq® (Asfotase Alfa)
NCT04222452	Not specified	UNKNOWN	The PORTRAIT Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ASFOTASE ALFA	4	16
BORTEZOMIB	4	1
FOLIC ACID	4	1
RITUXIMAB	4	1
SETRUSUMAB	3	1
EFZIMFOTASE ALFA	2	4
ILOFOTASE ALFA	2	1