Details of Disease

General Information of Disease (ID: DISVIZPC)

• Disease Name: Megaloblastic anemia
• Synonyms: IGS; recessive hereditary megaloblastic anemia 1; recessive hereditary megaloblastic anaemia 1; megaloblastic anemia (disease); megaloblastic anemia; megaloblastic anaemia (disease); RH-MGA1; MGA1 Norwegian type; Grasbeck-Imerslund syndrome
• Definition: Anemia characterized by the presence of unusually large erythroblasts in the bone marrow called megaloblasts. It is usually caused by vitamin B12 or folic acid deficiency. Other causes include toxins and drugs.
• Disease Hierarchy:
  :
  DISVIZPC: Megaloblastic anemia
• Disease Identifiers:
  MONDO ID: MONDO_0001700
  MESH ID: D000749
  UMLS CUI: C0002888
  MedGen ID: 1527
  HPO ID: HP:0001889
  SNOMED CT ID: 53165003

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 2 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Leucovorin	DMUAZWG	Approved	Small molecular drug	[1]
Levoleucovorin	DMH5LME	Approved	Small molecular drug	[2]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
MTR	TTUTO39	moderate	Altered Expression	[3]
SLC19A2	TT2A1DZ	moderate	Genetic Variation	[4]
UMPS	TTAFJUD	moderate	Genetic Variation	[5]
CUBN	TT9YLCR	Strong	Genetic Variation	[6]
DHFR	TTYZVDJ	Strong	Biomarker	[7]
MAOB	TTGP7BY	Strong	Biomarker	[8]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
MTRR	DE6NIY9	Limited	Genetic Variation	[9]

This Disease Is Related to 7 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
AMN	OTS1TJXG	Limited	Genetic Variation	[10]
MMACHC	OTX0TT3W	moderate	Genetic Variation	[11]
CBLIF	OTNE20WU	Strong	Biomarker	[12]
MTHFD1	OTMKHVWC	Strong	Biomarker	[13]
MTHFD1L	OTV01EFP	Strong	Genetic Variation	[14]
TCN1	OTW6A49Y	Strong	Biomarker	[15]
TCN2	OT41D0L3	Strong	Biomarker	[16]

References

• [1] Leucovorin FDA Label
• [2] Levoleucovorin FDA Label
• [3] Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria.Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3059-64. doi: 10.1073/pnas.95.6.3059.
• [4] A Novel Mutation of SLC19A2 in a Chinese Zhuang Ethnic Family with Thiamine-Responsive Megaloblastic Anemia.Cell Physiol Biochem. 2018;47(5):1989-1997. doi: 10.1159/000491467. Epub 2018 Jul 3.
• [5] Mild orotic aciduria in UMPS heterozygotes: a metabolic finding without clinical consequences.J Inherit Metab Dis. 2017 May;40(3):423-431. doi: 10.1007/s10545-017-0015-9. Epub 2017 Feb 15.
• [6] Isolated proteinuria due to CUBN homozygous mutation - challenging the investigative paradigm.BMC Nephrol. 2019 Aug 22;20(1):330. doi: 10.1186/s12882-019-1474-z.
• [7] Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency.Am J Hum Genet. 2011 Feb 11;88(2):216-25. doi: 10.1016/j.ajhg.2011.01.004.
• [8] Platelet monoamine oxidase activity in megaloblastic anaemia.J Clin Pathol. 1980 Oct;33(10):963-5. doi: 10.1136/jcp.33.10.963.
• [9] Polymorphic background of methionine synthase reductase modulates the phenotype of a disease-causing mutation.Hum Mutat. 2007 Oct;28(10):1028-33. doi: 10.1002/humu.20563.
• [10] Homozygous AMN mutation in hereditary selective intestinal malabsorption of vitamin B12 in Jordan.Saudi Med J. 2005 Jul;26(7):1061-4.
• [11] Interaction between methionine synthase isoforms and MMACHC: characterization in cblG-variant, cblG and cblC inherited causes of megaloblastic anaemia.Hum Mol Genet. 2013 Nov 15;22(22):4591-601. doi: 10.1093/hmg/ddt308. Epub 2013 Jul 3.
• [12] Steroid-responsive functional B12 deficiency in association with transcobalamin II polymorphism 776C --> G.Eur J Haematol. 2006 Jan;76(1):75-8. doi: 10.1111/j.1600-0609.2005.00563.x.
• [13] Precision Molecular Diagnosis Defines Specific Therapy in Combined Immunodeficiency with Megaloblastic Anemia Secondary to MTHFD1 Deficiency.J Allergy Clin Immunol Pract. 2016 Nov-Dec;4(6):1160-1166.e10. doi: 10.1016/j.jaip.2016.07.014. Epub 2016 Oct 1.
• [14] Update and new concepts in vitamin responsive disorders of folate transport and metabolism.J Inherit Metab Dis. 2012 Jul;35(4):665-70. doi: 10.1007/s10545-011-9418-1. Epub 2011 Nov 23.
• [15] Megaloblastic anemia after anticonvulsive therapy.N Engl J Med. 1972 Nov 9;287(19):990. doi: 10.1056/NEJM197211092871925.
• [16] Hereditary partial transcobalamin II deficiency with neurologic, mental and hematologic abnormalities in children and adults.Isr Med Assoc J. 2003 Dec;5(12):868-72.