Details of Disease

General Information of Disease (ID: DIS56N48)

Disease Name	Propionic acidemia
Synonyms	PCC deficiency; propionyl-Coa carboxylase deficiency; hyperglycinemia with ketoacidosis and leukopenia; prop; Glycinemia, ketotic; Propionicacidemia; ketotic II glycinemia; GLYCINEMIA, ketotic; ketotic glycinemia; ketotic hyperglycinemia; propionic acidemia; propionic aciduria; propionyl-CoA carboxylase deficiency
Disease Class	5C50: Metabolism inborn error
Definition	Propionic acidemia (PA) is an organic aciduria caused by the deficient activity of the propionyl Coenzyme A carboxylase and is characterized by life threatening episodes of metabolic decompensation, neurological dysfunction and that may be complicated by cardiomyopathy.
Disease Hierarchy	DISCXXVK: Classic organic aciduria DIS56N48: Propionic acidemia
ICD Code	ICD-11 ICD-11: 5C50.E0
Disease Identifiers	MONDO ID MONDO_0011628 MESH ID D056693 UMLS CUI C0268579 OMIM ID 606054 MedGen ID 75694 HPO ID HP:0003571 Orphanet ID 35 SNOMED CT ID 69080001

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
HST5040	DM13Y55	Phase 2	NA	[1]
mRNA-3927	DMQFPI1	Phase 2	mRNA therapy	[2]
BBP-671	DMR9XMZ	Phase 1	Small molecule	[3]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
PCCA	TT1JDE3	Limited	Biomarker	[4]
PCCB	TT5LURU	Limited	Genetic Variation	[5]
PCCA	TT1JDE3	Definitive	Autosomal recessive	[6]
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This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC22A5	DT3HUVD	Strong	Biomarker	[7]
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This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
NAGS	DEGI1A9	Strong	Genetic Variation	[8]
PCCB	DESWQMH	Definitive	Autosomal recessive	[6]
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This Disease Is Related to 6 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ARID4B	OTYLPILE	Strong	Altered Expression	[9]
CRYGD	OTW29JC4	Strong	Genetic Variation	[10]
KCNE1	OTZNQUW9	Strong	Biomarker	[11]
MCCC2	OTQDHSMI	Strong	Genetic Variation	[12]
PCCA	OTWJTCRK	Definitive	Autosomal recessive	[6]
PCCB	OTXUN47K	Definitive	Autosomal recessive	[6]
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⏷ Show the Full List of 6 DOT(s)

References

1	ClinicalTrials.gov (NCT04732429) A Phase 2 Open-label, Dose Escalation Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia Followed by a Randomized, Double-blind, Placebo-controlled, 2-period Crossover Study and an Open-label, Long-term Extension Study. U.S.National Institutes of Health.
2	ClinicalTrials.gov (NCT05130437) A Phase 1/2, Global, Open-Label, Extension Study to Evaluate the Long-Term Safety and Clinical Activity of mRNA-3927 in Participants Previously Enrolled in the mRNA-3927-P101 Study. U.S.National Institutes of Health.
3	ClinicalTrials.gov (NCT04836494) A First-in-human, Randomized, Placebo-controlled, Single and Multiple Ascending Dose Escalation to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BBP-671 in Healthy Subjects and In Patients With Propionic Acidemia or Methylmalonic Acidemia. U.S.National Institutes of Health.
4	Multi-omics studies in cellular models of methylmalonic acidemia and propionic acidemia reveal dysregulation of serine metabolism.Biochim Biophys Acta Mol Basis Dis. 2019 Dec 1;1865(12):165538. doi: 10.1016/j.bbadis.2019.165538. Epub 2019 Aug 23.
5	Generation and characterization of a human iPSC line (UAMi004-A) from a patient with propionic acidemia due to defects in the PCCB gene.Stem Cell Res. 2019 Jul;38:101469. doi: 10.1016/j.scr.2019.101469. Epub 2019 May 22.
6	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.
7	Advantages and pitfalls of an extended gene panel for investigating complex neurometabolic phenotypes.Brain. 2016 Nov 1;139(11):2844-2854. doi: 10.1093/brain/aww221.
8	Evaluation of long-term effectiveness of the use of carglumic acid in patients with propionic acidemia (PA) or methylmalonic acidemia (MMA): study protocol for a randomized controlled trial.BMC Pediatr. 2019 Jun 13;19(1):195. doi: 10.1186/s12887-019-1571-y.
9	Decreased plasma l-arginine levels in organic acidurias (MMA and PA) and decreased plasma branched-chain amino acid levels in urea cycle disorders as a potential cause of growth retardation: Options for treatment.Mol Genet Metab. 2019 Apr;126(4):397-405. doi: 10.1016/j.ymgme.2019.02.003. Epub 2019 Feb 25.
10	Propionic acidemia in the Arab World.Gene. 2015 Jun 15;564(2):119-24. doi: 10.1016/j.gene.2015.04.019. Epub 2015 Apr 9.
11	Possible mechanisms for sensorineural hearing loss and deafness in patients with propionic acidemia.Orphanet J Rare Dis. 2017 Feb 13;12(1):30. doi: 10.1186/s13023-017-0585-5.
12	Kinetic characterization of mutations found in propionic acidemia and methylcrotonylglycinuria: evidence for cooperativity in biotin carboxylase.J Biol Chem. 2004 Apr 16;279(16):15772-8. doi: 10.1074/jbc.M311982200. Epub 2004 Feb 11.