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Hereditary spherocytosis(SPH)

MedGen UID:
52450
Concept ID:
C0037889
Disease or Syndrome
Synonyms: Congenital spherocytic hemolytic anemia; Congenital spherocytosis; SPH
SNOMED CT: HS - Hereditary spherocytosis (55995005); Hereditary spherocytosis (55995005); Familial spherocytosis (55995005); Minkowsky-Chauffard syndrome (55995005); Congenital spherocytosis (55995005); Familial acholuric jaundice (55995005); Congenital spherocytic hemolytic anemia (55995005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: 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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: 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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Related genes: SPTB, SPTA1, SLC4A1, EPB42, ANK1
 
Monarch Initiative: MONDO:0019350
Orphanet: ORPHA822

Definition

Hereditary spherocytosis refers to a group of heterogeneous disorders that are characterized by the presence of spherical-shaped erythrocytes (spherocytes) on the peripheral blood smear. The disorders are characterized clinically by anemia, jaundice, and splenomegaly, with variable severity. Common complications include cholelithiasis, hemolytic episodes, and aplastic crises (review by Perrotta et al., 2008). Elgsaeter et al. (1986) gave an extensive review of the molecular basis of erythrocyte shape with a discussion of the role of spectrin and other proteins such as ankyrin, actin (102630), band 4.1 (130500), and band 3 (109270), all of which is relevant to the understanding of spherocytosis and elliptocytosis (see 611904). See Delaunay (2007) for a discussion of the molecular basis of hereditary red cell membrane disorders. Genetic Heterogeneity of Hereditary Spherocytosis Also see SPH2 (616649), caused by mutation in the SPTB gene (182870) on chromosome 14q23; SPH3 (270970), caused by mutation in the SPTA1 gene (182860) on chromosome 1q21; SPH4 (612653), caused by mutation in the SLC4A1 gene (109270) on chromosome 17q21; and SPH5 (612690), caused by mutation in the EPB42 gene (177070) on chromosome 15q15. [from OMIM]

Additional description

From MedlinePlus Genetics
Hereditary spherocytosis is a condition that affects red blood cells. People with this condition typically experience a shortage of red blood cells (anemia), yellowing of the eyes and skin (jaundice), and an enlarged spleen (splenomegaly). Most newborns with hereditary spherocytosis have severe anemia, although it improves after the first year of life. Splenomegaly can occur anytime from early childhood to adulthood. About half of affected individuals develop hard deposits in the gallbladder called gallstones, which typically occur from late childhood to mid-adulthood.

There are four forms of hereditary spherocytosis, which are distinguished by the severity of signs and symptoms. They are known as the mild form, the moderate form, the moderate/severe form, and the severe form. It is estimated that 20 to 30 percent of people with hereditary spherocytosis have the mild form, 60 to 70 percent have the moderate form, 10 percent have the moderate/severe form, and 3 to 5 percent have the severe form.

People with the mild form may have very mild anemia or sometimes have no symptoms. People with the moderate form typically have anemia, jaundice, and splenomegaly. Many also develop gallstones. The signs and symptoms of moderate hereditary spherocytosis usually appear in childhood. Individuals with the moderate/severe form have all the features of the moderate form but also have severe anemia. Those with the severe form have life-threatening anemia that requires frequent blood transfusions to replenish their red blood cell supply. They also have severe splenomegaly, jaundice, and a high risk for developing gallstones. Some individuals with the severe form have short stature, delayed sexual development, and skeletal abnormalities.  https://medlineplus.gov/genetics/condition/hereditary-spherocytosis

Professional guidelines

PubMed

Tole S, Dhir P, Pugi J, Drury LJ, Butchart S, Fantauzzi M, Langer JC, Baker JM, Blanchette VS, Kirby-Allen M, Carcao MD
Br J Haematol 2020 Nov;191(3):486-496. Epub 2020 May 20 doi: 10.1111/bjh.16750. PMID: 32436265
Manciu S, Matei E, Trandafir B
Chirurgia (Bucur) 2017 Mar-Apr;112(2):110-116. doi: 10.21614/chirurgia.112.2.110. PMID: 28463670
Bolton-Maggs PH, Langer JC, Iolascon A, Tittensor P, King MJ; General Haematology Task Force of the British Committee for Standards in Haematology
Br J Haematol 2012 Jan;156(1):37-49. Epub 2011 Nov 5 doi: 10.1111/j.1365-2141.2011.08921.x. PMID: 22055020

Recent clinical studies

Etiology

Neamţu SD, Novac MB, Neamţu AV, Stanca ID, Boldeanu MV, Gluhovschi A, Stanca L, Dijmărescu AL, Manolea MM, Trăistaru MR, Mateescu GO, Siminel MA
Rom J Morphol Embryol 2022 Jan-Mar;63(1):229-235. doi: 10.47162/RJME.63.1.26. PMID: 36074689Free PMC Article
Tole S, Dhir P, Pugi J, Drury LJ, Butchart S, Fantauzzi M, Langer JC, Baker JM, Blanchette VS, Kirby-Allen M, Carcao MD
Br J Haematol 2020 Nov;191(3):486-496. Epub 2020 May 20 doi: 10.1111/bjh.16750. PMID: 32436265
Jamwal M, Sharma P, Das R
Indian J Pediatr 2020 Jan;87(1):66-74. Epub 2019 Dec 10 doi: 10.1007/s12098-019-03119-8. PMID: 31823208
Manciu S, Matei E, Trandafir B
Chirurgia (Bucur) 2017 Mar-Apr;112(2):110-116. doi: 10.21614/chirurgia.112.2.110. PMID: 28463670
Perrotta S, Gallagher PG, Mohandas N
Lancet 2008 Oct 18;372(9647):1411-26. doi: 10.1016/S0140-6736(08)61588-3. PMID: 18940465

Diagnosis

Wu Y, Liao L, Lin F
J Clin Lab Anal 2021 Dec;35(12):e24034. Epub 2021 Oct 24 doi: 10.1002/jcla.24034. PMID: 34689357Free PMC Article
He BJ, Liao L, Deng ZF, Tao YF, Xu YC, Lin FQ
Acta Haematol 2018;139(1):60-66. Epub 2018 Jan 22 doi: 10.1159/000486229. PMID: 29402830
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Bellingham AJ, Prankerd TA
Clin Haematol 1975 Feb;4(1):139-44. PMID: 1102180

Therapy

Iolascon A, Andolfo I, Barcellini W, Corcione F, Garçon L, De Franceschi L, Pignata C, Graziadei G, Pospisilova D, Rees DC, de Montalembert M, Rivella S, Gambale A, Russo R, Ribeiro L, Vives-Corrons J, Martinez PA, Kattamis A, Gulbis B, Cappellini MD, Roberts I, Tamary H; Working Study Group on Red Cells and Iron of the EHA
Haematologica 2017 Aug;102(8):1304-1313. Epub 2017 May 26 doi: 10.3324/haematol.2016.161166. PMID: 28550188Free PMC Article
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Am Surg 1975 Sep;41(9):567-70. PMID: 1166975
Bellingham AJ, Prankerd TA
Clin Haematol 1975 Feb;4(1):139-44. PMID: 1102180

Prognosis

Principe DR, Reilly P, Dhavamani S, Rivers A, Molokie R, Hsu LL, Ramasamy J
J Pediatr Hematol Oncol 2024 Aug 1;46(6):e457-e462. Epub 2024 Jun 24 doi: 10.1097/MPH.0000000000002901. PMID: 38934620Free PMC Article
Yang L, Shu H, Zhou M, Gong Y
Clin Genet 2022 Dec;102(6):474-482. Epub 2022 Sep 26 doi: 10.1111/cge.14223. PMID: 36071563
Tole S, Dhir P, Pugi J, Drury LJ, Butchart S, Fantauzzi M, Langer JC, Baker JM, Blanchette VS, Kirby-Allen M, Carcao MD
Br J Haematol 2020 Nov;191(3):486-496. Epub 2020 May 20 doi: 10.1111/bjh.16750. PMID: 32436265
Boyd AS
Am Fam Physician 1989 Feb;39(2):167-72. PMID: 2644787
Westerman MP
Br J Haematol 1975 Sep;31(1):87-94. doi: 10.1111/j.1365-2141.1975.tb00835.x. PMID: 1212438

Clinical prediction guides

Pilgaard Kristiansen H, Winther-Larsen A
Clin Chim Acta 2023 Aug 1;548:117532. Epub 2023 Sep 1 doi: 10.1016/j.cca.2023.117532. PMID: 37659465
Neamţu SD, Novac MB, Neamţu AV, Stanca ID, Boldeanu MV, Gluhovschi A, Stanca L, Dijmărescu AL, Manolea MM, Trăistaru MR, Mateescu GO, Siminel MA
Rom J Morphol Embryol 2022 Jan-Mar;63(1):229-235. doi: 10.47162/RJME.63.1.26. PMID: 36074689Free PMC Article
Wu Y, Liao L, Lin F
J Clin Lab Anal 2021 Dec;35(12):e24034. Epub 2021 Oct 24 doi: 10.1002/jcla.24034. PMID: 34689357Free PMC Article
Tole S, Dhir P, Pugi J, Drury LJ, Butchart S, Fantauzzi M, Langer JC, Baker JM, Blanchette VS, Kirby-Allen M, Carcao MD
Br J Haematol 2020 Nov;191(3):486-496. Epub 2020 May 20 doi: 10.1111/bjh.16750. PMID: 32436265
Pogorelić Z, Aralica M, Jukić M, Žitko V, Despot R, Jurić I
Indian Pediatr 2019 May 15;56(5):384-386. Epub 2019 Mar 17 PMID: 30898989

Recent systematic reviews

Tang X, Xue J, Zhang J, Zhou J
Pediatr Surg Int 2024 Oct 29;40(1):280. doi: 10.1007/s00383-024-05879-7. PMID: 39470805
Li J, Wang X, Zheng N, Wang X, Liu Y, Xue L
BMC Med Genomics 2022 Dec 3;15(1):250. doi: 10.1186/s12920-022-01399-2. PMID: 36463227Free PMC Article
Silva R, Amarasinghe D, Perera S, Premawardhena A
Int J Lab Hematol 2022 Apr;44(2):248-262. Epub 2022 Jan 23 doi: 10.1111/ijlh.13800. PMID: 35068068
Schizas D, Katsaros I, Karatza E, Kykalos S, Spartalis E, Tsourouflis G, Dimitroulis D, Nikiteas N
J Laparoendosc Adv Surg Tech A 2020 Jul;30(7):730-736. Epub 2020 Mar 23 doi: 10.1089/lap.2020.0004. PMID: 32202962
Guizzetti L
Pediatr Blood Cancer 2016 Oct;63(10):1713-22. Epub 2016 Jun 14 doi: 10.1002/pbc.26106. PMID: 27300151

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