Details of Disease

General Information of Disease (ID: DISCQ0O2)

Disease Name	Hypophosphatasia
Synonyms	phosphoethanol-aminuria; childhood hypophosphatasia; hypophospatasia, childhood; hypophosphatasia mild; HPP; deficiency of alkaline phosphatase; phosphoethanolaminuria; deficiency of alkaline phosphatase (disorder) [ambiguous]; Rathburn disease
Disease Class	5C64: Mineral absorption/transport disorder
Definition	Hypophosphatasia (HPP) is a rare heritable metabolic disorder characterized by defective mineralization of bone and/or teeth in the presence of reduced activity of unfractionated serum alkaline phosphatase (ALP). The clinical spectrum is extremely wide, from stillbirth at one end to fractures of the lower extremities in adulthood, at the other, or even no bone manifestations (odontohypophosphatasia).
Disease Hierarchy	DISO5FAY: Inborn error of metabolism DISMFQKM: Developmental anomaly of metabolic origin DIS3HIWD: Autosomal dominant disease DISCQ0O2: Hypophosphatasia
ICD Code	ICD-11 ICD-11: 5C64.3 ICD-10 ICD-10: E83.3 ICD-9 ICD-9: 275.3 Expand ICD-11 '5C64.3 Expand ICD-10 'E83.3 Expand ICD-9 275.3
Disease Identifiers	MONDO ID MONDO_0018570 MESH ID D007014 UMLS CUI C0020630 MedGen ID 43799 Orphanet ID 436 SNOMED CT ID 190859005

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 3 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Calcium Acetate	DM40MBV	Approved	Small molecular drug	[1]
Lanthanum carbonate	DMMJQSH	Approved	Small molecular drug	[2]
Sevelamer hydrochloride	DM8NFHA	Approved	Small molecular drug	[1]
------------------------------------------------------------------------------------

This Disease is Treated as An Indication in 8 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
ASP1585	DMNKO0I	Phase 3	Small molecular drug	[3]
KRN-23	DMMZWGK	Phase 3	NA	[4]
SBR-759	DMEJB2Y	Phase 3	NA	[5]
Z-521	DM8COV0	Phase 3	NA	[6]
Genz-644470	DM2FQO3	Phase 2	NA	[7]
ALXN1850	DMSQPCT	Phase 1	Enzyme replacement	[8]
Fostrap	DMW03PJ	Phase 1	NA	[9]
SPI-014	DM5IPUS	Phase 1	NA	[10]
------------------------------------------------------------------------------------


⏷ Show the Full List of 8 Drug(s)

This Disease is Treated as An Indication in 1 Discontinued Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
VML-252	DM7HBIX	Discontinued in Phase 2	NA	[11]
------------------------------------------------------------------------------------

This Disease is Treated as An Indication in 4 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
JPH-101	DM4OTZ1	Investigative	NA	[12]
Lanthanum polystyrene sulfonate	DME6NOY	Investigative	NA	[12]
Phosphatonin	DMNNRA4	Investigative	NA	[12]
RDX-002	DMLQQ9C	Investigative	NA	[12]
------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ASRGL1	TT4WT91	Limited	Biomarker	[13]
ALPL	TTMR5UV	Strong	Genetic Variation	[14]
CACNA1F	TTJ0SO4	Strong	Biomarker	[15]
P2RX7	TT473XN	Strong	Biomarker	[16]
PDXP	TT9UYG4	Strong	Altered Expression	[13]
PRDX5	TTLPJWH	Strong	Altered Expression	[13]
------------------------------------------------------------------------------------


⏷ Show the Full List of 6 DTT(s)

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
NAT10	DEZV4AP	Limited	Biomarker	[13]
ALPL	DEVEFKM	Definitive	Autosomal recessive	[17]
------------------------------------------------------------------------------------

This Disease Is Related to 12 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ALPP	OTZU4G9W	Limited	Biomarker	[13]
ATRNL1	OTY5JUX2	Limited	Biomarker	[13]
CCL27	OTUZYC61	Limited	Biomarker	[13]
PDLIM3	OTVXQC81	Limited	Biomarker	[13]
SLPI	OTUNFUU8	Limited	Biomarker	[13]
MYBPC1	OTRPN93S	Strong	Genetic Variation	[15]
PIGT	OTWA8819	Strong	Genetic Variation	[18]
PLP1	OT8CM9CX	Strong	Altered Expression	[13]
PLPBP	OT9DZ8P6	Strong	Biomarker	[19]
SFTPB	OTOHS07E	Strong	Altered Expression	[20]
ALPL	OTG7J4BP	Definitive	Autosomal recessive	[17]
DLX3	OTARP5SQ	Definitive	Genetic Variation	[21]
------------------------------------------------------------------------------------


⏷ Show the Full List of 12 DOT(s)

References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2	2004 approvals: the demise of the blockbuster. Nat Rev Drug Discov. 2005 Feb;4(2):93-4.
3	ClinicalTrials.gov (NCT01742611) Long-term Study in Chronic Kidney Disease Patients With Hyperphosphatemia Not on Dialysis. U.S. National Institutes of Health.
4	ClinicalTrials.gov (NCT02526160) Study of KRN23 in Adults With X-linked Hypophosphatemia (XLH).
5	ClinicalTrials.gov (NCT01069692) Placebo Versus SBR759 in Lowering Phosphate in Dialysis Patients. U.S. National Institutes of Health.
6	ClinicalTrials.gov (NCT01237288) Therapeutic Use of Oral Sodium Phosphate (Z-521) in Primary Hypophosphatemic Rickets. U.S. National Institutes of Health.
7	ClinicalTrials.gov (NCT00853242) Randomized Study Comparing Genz-644470, Placebo, and Sevelamer Carbonate in Chronic Kidney Disease Patients on Hemodialysis. U.S. National Institutes of Health.
8	ClinicalTrials.gov (NCT04980248) A Phase 1, Open-label, Dose-escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALXN1850 in Adults With Hypophosphatasia. U.S.National Institutes of Health.
9	ClinicalTrials.gov (NCT01057108) Double Blind Randomized Placebo Controlled Trial of FOSTRAP Chewing Gum in Patients With CKD and Hyperphosphatemia. U.S. National Institutes of Health.
10	ClinicalTrials.gov (NCT01560884) Study to Assess the Safety and the Phosphate Binding Capacity of Renazorb. U.S. National Institutes of Health.
11	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008643)
12	The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
13	HYPOPHOSPHATASIA: CLINICAL ASSESSMENT AND MANAGEMENT IN THE ADULT PATIENT-A NARRATIVE REVIEW.Endocr Pract. 2018 Dec;24(12):1086-1092. doi: 10.4158/EP-2018-0194. Epub 2018 Oct 5.
14	Hypophosphatasia in Japan: ALPL Mutation Analysis in 98 Unrelated Patients.Calcif Tissue Int. 2020 Mar;106(3):221-231. doi: 10.1007/s00223-019-00626-w. Epub 2019 Nov 9.
15	Unique disease heritage of the Dutch-German Mennonite population.Am J Med Genet A. 2008 Apr 15;146A(8):1072-87. doi: 10.1002/ajmg.a.32061.
16	Neurodevelopmental alterations and seizures developed by mouse model of infantile hypophosphatasia are associated with purinergic signalling deregulation.Hum Mol Genet. 2016 Oct 1;25(19):4143-4156. doi: 10.1093/hmg/ddw248. Epub 2016 Jul 27.
17	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
18	Novel compound heterozygous PIGT mutations caused multiple congenital anomalies-hypotonia-seizures syndrome 3.Neurogenetics. 2014 Aug;15(3):193-200. doi: 10.1007/s10048-014-0408-y. Epub 2014 Jun 8.
19	Disorders affecting vitamin B(6) metabolism.J Inherit Metab Dis. 2019 Jul;42(4):629-646. doi: 10.1002/jimd.12060. Epub 2019 Mar 20.
20	An alternatively spliced surfactant protein B mRNA in normal human lung: disease implication.Biochem J. 1999 Oct 1;343 Pt 1(Pt 1):145-9.
21	Developmental biology and genetics of dental malformations.Orthod Craniofac Res. 2007 May;10(2):45-52. doi: 10.1111/j.1601-6343.2007.00384.x.