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Hereditary spherocytosis type 3(SPH3; HS3)

MedGen UID:
394798
Concept ID:
C2678338
Disease or Syndrome
Synonyms: Spherocytosis type 3; SPTA1-Related Hereditary Spherocytosis; SPTA1-Related Spherocytosis
 
Gene (location): SPTA1 (1q23.1)
 
Monarch Initiative: MONDO:0010053
OMIM®: 270970

Definition

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. [from MedlinePlus Genetics]

Clinical features

From HPO
Hemolytic anemia
MedGen UID:
1916
Concept ID:
C0002878
Disease or Syndrome
A type of anemia caused by premature destruction of red blood cells (hemolysis).
Spherocytosis
MedGen UID:
154301
Concept ID:
C0553720
Finding
The presence of erythrocytes that are sphere-shaped.

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
MACKINNEY AA Jr, MORTONNE, KOSOWER NS, SCHILLING RF
J Clin Invest 1962 Mar;41(3):554-67. doi: 10.1172/JCI104509. PMID: 14467968Free PMC Article
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J Pediatr 1957 Mar;50(3):308-14. doi: 10.1016/s0022-3476(57)80028-6. PMID: 13406684

Recent clinical studies

Etiology

Aly NH, Elalfy MS, Elhabashy SA, Mowafy NM, Russo R, Andolfo I, Iolascon A, Ragab IA
Blood Cells Mol Dis 2023 Nov;103:102779. Epub 2023 Jul 16 doi: 10.1016/j.bcmd.2023.102779. PMID: 37558589
Wang WJ, Xie JD, Yao H, Ding ZX, Jiang AR, Ma L, Shen HJ, Chen SN
Clin Genet 2023 Jan;103(1):67-78. Epub 2022 Oct 21 doi: 10.1111/cge.14244. PMID: 36203343
Garzón G LN, Jaramillo B LE, Valero H JJ, Quintero C EM
J Pediatr Surg 2021 Mar;56(3):550-552. Epub 2020 Jun 3 doi: 10.1016/j.jpedsurg.2020.05.039. PMID: 32624207
Zaninoni A, Fermo E, Vercellati C, Marcello AP, Barcellini W, Bianchi P
Front Immunol 2020;11:1309. Epub 2020 Jun 23 doi: 10.3389/fimmu.2020.01309. PMID: 32655575Free 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

Diagnosis

Aly NH, Elalfy MS, Elhabashy SA, Mowafy NM, Russo R, Andolfo I, Iolascon A, Ragab IA
Blood Cells Mol Dis 2023 Nov;103:102779. Epub 2023 Jul 16 doi: 10.1016/j.bcmd.2023.102779. PMID: 37558589
Garzón G LN, Jaramillo B LE, Valero H JJ, Quintero C EM
J Pediatr Surg 2021 Mar;56(3):550-552. Epub 2020 Jun 3 doi: 10.1016/j.jpedsurg.2020.05.039. PMID: 32624207
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
Lang F, Qadri SM
Blood Purif 2012;33(1-3):125-30. Epub 2012 Jan 20 doi: 10.1159/000334163. PMID: 22269222
Tse WT, Lux SE
Br J Haematol 1999 Jan;104(1):2-13. doi: 10.1111/j.1365-2141.1999.01130.x. PMID: 10027705

Therapy

Mack SJ, Pace DJ, Patil S, Cooke-Barber J, Boelig MM, Berman L
J Pediatr Surg 2024 Jan;59(1):117-123. Epub 2023 Sep 21 doi: 10.1016/j.jpedsurg.2023.09.010. PMID: 37833213
Elbadry MI, Khaled SAA, Ahmed NM, Abudeif A, Abdelkareem RM, Ezeldin M, Tawfeek A
Br J Haematol 2021 May;193(4):827-840. Epub 2021 Apr 25 doi: 10.1111/bjh.17484. PMID: 33899219
Englum BR, Rothman J, Leonard S, Reiter A, Thornburg C, Brindle M, Wright N, Heeney MM, Jason Smithers C, Brown RL, Kalfa T, Langer JC, Cada M, Oldham KT, Scott JP, St Peter SD, Sharma M, Davidoff AM, Nottage K, Bernabe K, Wilson DB, Dutta S, Glader B, Crary SE, Dassinger MS, Dunbar L, Islam S, Kumar M, Rescorla F, Bruch S, Campbell A, Austin M, Sidonio R, Blakely ML, Rice HE; Splenectomy in Congenital Hemolytic Anemia Consortium
J Pediatr Surg 2016 Jan;51(1):122-7. Epub 2015 Oct 23 doi: 10.1016/j.jpedsurg.2015.10.028. PMID: 26613837Free PMC Article
Vecchio R, Intagliata E, Marchese S, Battaglia S, Cacciola RR, Cacciola E
G Chir 2015 May-Jun;36(3):101-5. PMID: 26188753Free PMC Article
Hughes MR, Anderson N, Maltby S, Wong J, Berberovic Z, Birkenmeier CS, Haddon DJ, Garcha K, Flenniken A, Osborne LR, Adamson SL, Rossant J, Peters LL, Minden MD, Paulson RF, Wang C, Barber DL, McNagny KM, Stanford WL
Exp Hematol 2011 Mar;39(3):305-20, 320.e1-2. Epub 2010 Dec 28 doi: 10.1016/j.exphem.2010.12.009. PMID: 21193012Free PMC Article

Prognosis

Campbell-Washburn AE, Mancini C, Conrey A, Edwards L, Shanbhag S, Wood J, Xue H, Kellman P, Bandettini WP, Thein SL
J Magn Reson Imaging 2022 Jun;55(6):1855-1863. Epub 2021 Oct 20 doi: 10.1002/jmri.27950. PMID: 34668604Free PMC Article
Garzón G LN, Jaramillo B LE, Valero H JJ, Quintero C EM
J Pediatr Surg 2021 Mar;56(3):550-552. Epub 2020 Jun 3 doi: 10.1016/j.jpedsurg.2020.05.039. PMID: 32624207
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
Lorand L, Iismaa SE
FASEB J 2019 Jan;33(1):3-12. doi: 10.1096/fj.201801544R. PMID: 30593123
Ruparel RK, Bogert JN, Moir CR, Ishitani MB, Khan SP, Rodriguez V, Zarroug AE
J Pediatr Surg 2014 Mar;49(3):433-5. doi: 10.1016/j.jpedsurg.2013.05.012. PMID: 24650472

Clinical prediction guides

Wang WJ, Xie JD, Yao H, Ding ZX, Jiang AR, Ma L, Shen HJ, Chen SN
Clin Genet 2023 Jan;103(1):67-78. Epub 2022 Oct 21 doi: 10.1111/cge.14244. PMID: 36203343
Campbell-Washburn AE, Mancini C, Conrey A, Edwards L, Shanbhag S, Wood J, Xue H, Kellman P, Bandettini WP, Thein SL
J Magn Reson Imaging 2022 Jun;55(6):1855-1863. Epub 2021 Oct 20 doi: 10.1002/jmri.27950. PMID: 34668604Free 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
Lorand L, Iismaa SE
FASEB J 2019 Jan;33(1):3-12. doi: 10.1096/fj.201801544R. PMID: 30593123
Rocha S, Rebelo I, Costa E, Catarino C, Belo L, Castro EM, Cabeda JM, Barbot J, Quintanilha A, Santos-Silva A
Eur J Haematol 2005 May;74(5):374-80. doi: 10.1111/j.1600-0609.2004.00385.x. PMID: 15813910

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