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Hemolytic anemia, nonspherocytic, due to glucose phosphate isomerase deficiency

MedGen UID:
462080
Concept ID:
C3150730
Disease or Syndrome
Synonyms: HEMOLYTIC ANEMIA, NONSPHEROCYTIC, DUE TO GLUCOSE PHOSPHATE ISOMERASE DEFICIENCY
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
 
Gene (location): GPI (19q13.11)
OMIM®: 613470
Orphanet: ORPHA712

Definition

Glucose phosphate isomerase (GPI) deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the body's tissues. People with this disorder have a condition known as chronic hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). Chronic hemolytic anemia can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), extreme tiredness (fatigue), shortness of breath (dyspnea), and a rapid heart rate (tachycardia). An enlarged spleen (splenomegaly), an excess of iron in the blood, and small pebble-like deposits in the gallbladder or bile ducts (gallstones) may also occur in this disorder.Hemolytic anemia in GPI deficiency can range from mild to severe. In the most severe cases, affected individuals do not survive to birth. Individuals with milder disease can survive into adulthood. People with any level of severity of the disorder can have episodes of more severe hemolysis, called hemolytic crises, which can be triggered by bacterial or viral infections.A small percentage of individuals with GPI deficiency also have neurological problems, including intellectual disability and difficulty with coordinating movements (ataxia).
[from GHR]

Clinical features

Impaired neutrophil bactericidal activity
MedGen UID:
868687
Concept ID:
C4023090
Finding
A reduction in the ability of neutrophils to kill bacteria.
Spontaneous hemolytic crises
MedGen UID:
870730
Concept ID:
C4025184
Disease or Syndrome
Nonspherocytic hemolytic anemia
MedGen UID:
871250
Concept ID:
C4025735
Disease or Syndrome
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Sign or Symptom
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Intellectual functioning disability
MedGen UID:
7544
Concept ID:
C0025362
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Spinal ataxia
MedGen UID:
508159
Concept ID:
C0037921
Disease or Syndrome
Incoordination of movement caused by a deficit in the sensory nervous system. Sensory ataxia can be distinguished from cerebellar ataxia by asking the patient to close his or her eyes. Persons with cerebellar ataxia show only a minimal worsening of symptoms, whereas persons with sensory ataxia show a marked worsening of symptoms.
Cholecystitis
MedGen UID:
920
Concept ID:
C0008325
Disease or Syndrome
In general, gallbladder disease (GBD) is one of the major digestive diseases. GBD prevalence is particularly high in some minority populations in the United States, including Native and Mexican Americans. Gallstones composed of cholesterol (cholelithiasis) are the common manifestations of GBD in western countries, including the United States. Most people with gallstones remain asymptomatic through their lifetimes; however, it is estimated that approximately 10 to 50% of individuals eventually develop symptoms. Significant risk factors associated with GBD are age, female sex, obesity (especially central obesity), lipids, diet, parity, type 2 diabetes (125853), medications, and Mexican American ethnicity. GBD appears to be strongly related to the metabolic syndrome (605552) and/or its major components, such as hyperinsulinism, dyslipidemia, and abdominal adiposity (Boland et al., 2002; Tsai et al., 2004). Infection, specifically by Helicobacter, has been implicated in cholelithiasis and cholecystitis (Silva et al., 2003; Maurer et al., 2005). Low phospholipid-associated cholelithiasis is a specific form of gallbladder disease characterized by young-adult onset of chronic cholestasis with intrahepatic sludge and cholesterol cholelithiasis. Affected individuals have recurrence of the disorder after cholecystectomy and show a favorable response to treatment with ursodeoxycholic acid (UDCA) (summary by Pasmant et al., 2012). Mutation in the ABCB4 gene can cause a spectrum of related diseases, including the more severe progressive familial intrahepatic cholestasis-3 (PFIC3; 602347), intrahepatic cholestasis of pregnancy-3 (ICP3; 614972), andoral contraceptive-induced cholestasis (OCIC; see 614972). Genetic Heterogeneity of Gallbladder Disease Two major susceptibility loci for symptomatic gallbladder disease have been identified on chromosome 1p in Mexican Americans (GBD2, 609918; GBD3, 609919). In addition, variations in the ABCG8 gene (605460) on chromosome 2p21 confer susceptibility to gallbladder disease (GBD4; 611465).
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Pathologic Function
Jaundice causes your skin and the whites of your eyes to turn yellow. Too much bilirubin causes jaundice. Bilirubin is a yellow chemical in hemoglobin, the substance that carries oxygen in your red blood cells. As red blood cells break down, your body builds new cells to replace them. The old ones are processed by the liver. If the liver cannot handle the blood cells as they break down, bilirubin builds up in the body and your skin may look yellow. . Many healthy babies have some jaundice during the first week of life. It usually goes away. However, jaundice can happen at any age and may be a sign of a problem. Jaundice can happen for many reasons, such as. - Blood diseases. - Genetic syndromes. - Liver diseases, such as hepatitis or cirrhosis. - Blockage of bile ducts . - Infections . - Medicines .
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Pigment gallstones
MedGen UID:
480495
Concept ID:
C3278865
Finding
Gallstones composed primarily of bilirubin and calcium salts (calcium bilirubinate) with a low cholesterol concentration.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Impaired neutrophil bactericidal activity
MedGen UID:
868687
Concept ID:
C4023090
Finding
A reduction in the ability of neutrophils to kill bacteria.
Deficiency of glucose-6-phosphate isomerase
MedGen UID:
488961
Concept ID:
C1291611
Disease or Syndrome
A decreased rate of glucose-6-phosphate isomerase activity.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Pathologic Function
Jaundice causes your skin and the whites of your eyes to turn yellow. Too much bilirubin causes jaundice. Bilirubin is a yellow chemical in hemoglobin, the substance that carries oxygen in your red blood cells. As red blood cells break down, your body builds new cells to replace them. The old ones are processed by the liver. If the liver cannot handle the blood cells as they break down, bilirubin builds up in the body and your skin may look yellow. . Many healthy babies have some jaundice during the first week of life. It usually goes away. However, jaundice can happen at any age and may be a sign of a problem. Jaundice can happen for many reasons, such as. - Blood diseases. - Genetic syndromes. - Liver diseases, such as hepatitis or cirrhosis. - Blockage of bile ducts . - Infections . - Medicines .

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHemolytic anemia, nonspherocytic, due to glucose phosphate isomerase deficiency
Follow this link to review classifications for Hemolytic anemia, nonspherocytic, due to glucose phosphate isomerase deficiency in Orphanet.

Recent clinical studies

Etiology

Warang P, Kedar P, Ghosh K, Colah RB
Int J Hematol 2012 Aug;96(2):263-7. Epub 2012 Jul 11 doi: 10.1007/s12185-012-1122-x. [Epub ahead of print] PMID: 22782259
Jacobasch G, Rapoport SM
Mol Aspects Med 1996 Apr;17(2):143-70. PMID: 8813716
Xu W, Beutler E
J Clin Invest 1994 Dec;94(6):2326-9. doi: 10.1172/JCI117597. PMID: 7989588Free PMC Article
Rijksen G, Jansen G, Manaster J, Ezekiel E, Streichman S, Staal GE
Isr J Med Sci 1984 Jun;20(6):529-34. PMID: 6469574
Blume KG, Hryniuk W, Powars D, Trinidad F, West C, Beutler E
J Lab Clin Med 1972 Jun;79(6):942-9. PMID: 5025461

Diagnosis

Warang P, Kedar P, Ghosh K, Colah RB
Int J Hematol 2012 Aug;96(2):263-7. Epub 2012 Jul 11 doi: 10.1007/s12185-012-1122-x. [Epub ahead of print] PMID: 22782259
Rossi F, Ruggiero S, Gallo M, Simeone G, Matarese SM, Nobili B
Ann Pharmacother 2010 Jul-Aug;44(7-8):1327-9. Epub 2010 Jun 1 doi: 10.1345/aph.1P030. [Epub ahead of print] PMID: 20516363
Hirono A, Forman L, Beutler E
Medicine (Baltimore) 1988 Mar;67(2):110-7. PMID: 3352512
Whitelaw AG, Rogers PA, Hopkinson DA, Gordon H, Emerson PM, Darley JH, Reid C, Crawfurd MA
J Med Genet 1979 Jun;16(3):189-96. PMID: 469896Free PMC Article
Helleman PW, Van Biervliet JP
Helv Paediatr Acta 1976 Apr;30(6):525-36. PMID: 1270325

Therapy

Rossi F, Ruggiero S, Gallo M, Simeone G, Matarese SM, Nobili B
Ann Pharmacother 2010 Jul-Aug;44(7-8):1327-9. Epub 2010 Jun 1 doi: 10.1345/aph.1P030. [Epub ahead of print] PMID: 20516363
Schröter W
Eur J Pediatr 1980 Oct;135(1):41-3. PMID: 7449787
Fielek S, Mohrenweiser HW
Clin Chem 1979 Mar;25(3):384-8. PMID: 162438
Paglia DE, Valentine WN
Am J Clin Pathol 1974 Dec;62(6):740-51. PMID: 4611197

Prognosis

Clarke JL, Vulliamy TJ, Roper D, Mesbah-Namin SA, Wild BJ, Walker JI, Will AM, Bolton-Maggs PH, Mason PJ, Layton DM
Blood Cells Mol Dis 2003 May-Jun;30(3):258-63. PMID: 12737943
Huppke P, Wünsch D, Pekrun A, Kind R, Winkler H, Schröter W, Lakomek M
Eur J Pediatr 1997 Aug;156(8):605-9. PMID: 9266190
Baronciani L, Zanella A, Bianchi P, Zappa M, Alfinito F, Iolascon A, Tannoia N, Beutler E, Sirchia G
Blood 1996 Sep 15;88(6):2306-10. PMID: 8822952
Jacobasch G, Rapoport SM
Mol Aspects Med 1996 Apr;17(2):143-70. PMID: 8813716
Hutton JJ, Chilcote RR
J Pediatr 1974 Oct;85(4):494-7. PMID: 4443856

Clinical prediction guides

Rossi F, Ruggiero S, Gallo M, Simeone G, Matarese SM, Nobili B
Ann Pharmacother 2010 Jul-Aug;44(7-8):1327-9. Epub 2010 Jun 1 doi: 10.1345/aph.1P030. [Epub ahead of print] PMID: 20516363
Clarke JL, Vulliamy TJ, Roper D, Mesbah-Namin SA, Wild BJ, Walker JI, Will AM, Bolton-Maggs PH, Mason PJ, Layton DM
Blood Cells Mol Dis 2003 May-Jun;30(3):258-63. PMID: 12737943
Kugler W, Breme K, Laspe P, Muirhead H, Davies C, Winkler H, Schröter W, Lakomek M
Hum Genet 1998 Oct;103(4):450-4. PMID: 9856489
Rijksen G, Jansen G, Manaster J, Ezekiel E, Streichman S, Staal GE
Isr J Med Sci 1984 Jun;20(6):529-34. PMID: 6469574
Hutton JJ, Chilcote RR
J Pediatr 1974 Oct;85(4):494-7. PMID: 4443856

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