Hereditary Hemolytic Anemia Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
12041 ADA 81479,81479 Order Options and Pricing
AK1 81479,81479
ALDOA 81479,81479
ANK1 81479,81479
ATP11C 81479,81479
CD59 81479,81479
CDAN1 81479,81479
CDIN1 81479,81479
COL4A1 81408,81479
EPB41 81479,81479
EPB42 81479,81479
G6PD 81249,81479
GATA1 81479,81479
GCLC 81479,81479
GPI 81479,81479
GPX1 81479,81479
GSR 81479,81479
GSS 81479,81479
HK1 81479,81479
KCNN4 81479,81479
KIF23 81479,81479
KLF1 81479,81479
NT5C3A 81479,81479
PFKL 81479,81479
PFKM 81479,81479
PGK1 81479,81479
PIEZO1 81479,81479
PKLR 81405,81479
RHAG 81479,81479
SEC23B 81479,81479
SLC4A1 81479,81479
SPTA1 81479,81479
SPTB 81479,81479
TPI1 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
12041Genes x (34)81479 81249, 81405, 81408, 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Hemolytic anemia is caused by premature destruction of red blood cells (RBC). This can be cause by both intrinsic factors such as inherited conditions or extrinsic factors such as autoimmunities, drugs, microangiopathies, and hypersplenism. Intrinsic hemolytic anemias are largely divided into three categories: hemogloblinopathies, erythrocyte membrane defects and enzyme deficiencies. Hemoglobinopathy testing is available separately and not included in this panel due to different testing methodologies. The most common erythrocyte membrane defect is hereditary spherocytosis which affects 1 in 2,000 individuals. Other erythrocyte membrane defects include elliptocytosis, stomatocytosis, ovalocytosis and pyropoikilocytosis (An and Mohandas. 2008. PubMed ID: 18341630). With red blood cells relying on the glycolytic pathway for ATP production, several enzyme defects in this pathway are associated with hemolytic anemia. Glucose-6-phosphate dehydrogenase deficiency is the most prominent enzyme deficiency affecting over 400 million people worldwide. Congenital dyserythropoietic anemia (CDA) also shares some clinical characteristics of hemolytic anemia (Iolascon et al. 2012. PubMed ID: 23940284). Hemolytic anemia severity can range from asymptomatic mild hemolysis to life threatening severe hemolysis with onset at birth. Genetic testing can be helpful for differential diagnosis of intrinsic versus extrinsic forms of hemolytic anemia and for accurate diagnosis of intrinsic hemolytic anemia (Kim et al. 2017. PubMed ID: 28698843; Risinger et al. 2019. PubMed ID: 31030808).

Genetics

Hereditary spherocytosis (HS) in inherited in an autosomal dominant manner in 75% of cases through pathogenic variants in the ANK1, SPTB, and SLC4A1 genes. Autosomal recessive forms are primarily inherited through pathogenic variants in the SPTA1 gene (Bolton-Maggs et al. 2012. PubMed ID: 22055020). A founder variant in Eastern Europeans, designated c.4339-99C>T or Lepra, is the most common pathogenic variant in the SPTA1 gene. In general, truncating variants in the SPTB gene are associated with autosomal dominant forms of HS, whereas missense variants are more commonly found in autosomal recessive forms. Most pathogenic variants reported to date in HS related genes are private truncating variants (Park. 2016. PubMed ID: 26830532; Wang. 2018. PubMed ID: 29572776). Pathogenic variants in the ANK1, SPTB, SLC4A1, SPTA1, and EPB42 genes account for 60%, 10%, 15%, 10%, and 5% cases of HS respectively (An and Mohandas. 2008. PubMed ID: 18341630). About 30% of HS cases are de novo with no family history. Copy number variants have only been reported in a few cases.

Red blood cell enzymopathies are due to defects in genes in the glycolytic pathway. These disorders are inherited in an autosomal recessive manner through pathogenic variants in the AK1, ALDOA, GCLC, GPI, GPX1, GSR, GSS, HK1, NT5C3A, PFKL, PFKM, PKLR, and TPI1 genes and through an X-linked manner through the G6PD and PGK1 genes. Pathogenic variants in the G6PD and PKLR genes represent the most common red blood cell enzymopathies with missense changes being most frequent: ~85% and ~70% respectively (Kim et al. 2017. PubMed ID: 28698843; Risinger et al. 2019. PubMed ID: 31030808). Both hemizygous males and homozygous females have been reported with glucose-6-phosphate dehydrogenase deficiency. The majority of G6PD variants are founder variants which were selected due to providing protection from malarial infections (Kim et al. 2017. PubMed ID: 28698843).

Congenital dyserythropoietic anemia (CDA) is inherited in an autosomal recessive manner through pathogenic variants in the CDAN1, CDIN1/C15ORF41, and SEC23B genes, in an autosomal dominant manner through pathogenic variants in the KLF1 and KIF23 genes, and in an X-linked manner through the GATA1 gene. Type II CDA, the most common form with about 450 cases worldwide, is characterized by mild to severe anemia through pathogenic variants in the SEC23B gene (Iolascon et al. 2012. PubMed ID: 23940284). Copy number variants have rarely been reported in patients with CDA.

Hereditary xerocytosis (HX) or dehydrated stomatocytosis is inherited in an autosomal dominant manner through pathogenic variants in the PIEZO1 and KCNN4 genes. Gain of function missense variants in the PIEZO1 gene results in increased permeability of cations resulting in HX (Albuisson et al. 2013. PubMed ID: 23695678; Andolfo et al. 2013. PubMed ID: 23479567).

See individual gene and/or panel summaries for more information about molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

In a series of 195 cases of hereditary hemolytic anemia in Korea, 192 patients had positive genetic findings with erythrocyte membrane defects, hemoglobinopathies, and enzyme deficiencies representing 64.8%, 19.9% and 13.3% of cases (Park et al. 2013. PubMed ID: 24086942). In a separate study of 17 individuals, including patients with extreme hyperbilirubinemia or transfusion dependent, a genetic diagnosis was achieved in 12 cases with erythrocyte membrane defects being most prevalent (Agarwal et al. 2016. PubMed ID: 27292444).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.8% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Patients with hemolytic anemia may present pallor, fatigue, hyperbilirubinemia/jaundice, dark urine, gall stones and/or splenomegaly. Laboratory findings often include decreased hemoglobin concentration, hematocrit, red blood cell count, and elevated reticulocyte levels. Peripheral blood smears showing abnormal red blood cell morphology such as microcytes, spherocytes, stomatocytes, or elliptocytes are also characteristic of different anemias (Kim et al. 2017. PubMed ID: 28698843; Risinger et al. 2019. PubMed ID: 31030808).

Diseases

Name Inheritance OMIM ID
Adenylate Kinase Deficiency, Hemolytic Anemia Due To AR 612631
Angiopathy, Hereditary, With Nephropathy, Aneurysms, And Muscle Cramps AD 611773
Cd59 Deficiency AR 612300
Dyserythropoietic Anemia, Congenital, Type Ia AR 224120
Dyserythropoietic Anemia, Congenital, Type Ib AR 615631
Dyserythropoietic Anemia, Congenital, Type II AR 224100
Dyserythropoietic Anemia, Congenital, Type IV AD 613673
Elliptocytosis 1 AR 611804
Elliptocytosis 2 AD 130600
Gamma-Glutamylcysteine Synthetase Deficiency, Hemolytic Anemia Due To AR 230450
GATA-1-Related Thrombocytopenia With Dyserythropoiesis XL 300367
Glutathione Peroxidase Deficiency AR 614164
Glutathione Synthetase Deficiency Of Erythrocytes, Hemolytic Anemia Due To AR 231900
Gluthathione Synthetase Deficiency AR 266130
Glycogen Storage Disease Type VII AR 232800
Glycogen Storage Disease Type XII AR 611881
Hemolytic anemia due to G6PD deficiency XL 300908
Hemolytic anemia due to glutathione reductase deficiency AR 618660
Hemolytic Anemia Due To Hexokinase Deficiency AR 235700
Hemolytic Anemia due to Triosephosphate Isomerase Deficiency AR 615512
Hemolytic anemia, congenital, X-linked XL 301015
Hemolytic Anemia, Nonspherocytic, Due To Glucose Phosphate Isomerase Deficiency AR 613470
Hereditary Pyropoikilocytosis AR 266140
Hereditary Spherocytosis AR 182900
Lymphedema, Hereditary, III AR 616843
Microangiopathy and leukoencephalopathy, pontine, autosomal dominant AD 618564
Ovalocytosis, SA type AD 166900
Phosphoglycerate Kinase 1 Deficiency XL 300653
Porencephaly 1 AD 175780
Pyruvate Kinase Deficiency AR 266200
Retinal arteries, tortuosity of AD 180000
Rh-Null, Regulator Type AD 268150
Severe Combined Immunodeficiency Due To Ada Deficiency AR 102700
Spherocytosis, type 2 AD, AR 616649
Spherocytosis, Type 3 AR 270970
Spherocytosis, Type 4 AD 612653
Spherocytosis, Type 5 AR 612690
Stomatocytosis I AD 185000
Thrombocytopenia, Platelet Dysfunction, Hemolysis, And Imbalanced Globin Synthesis XL 314050
Uridine 5-Prime Monophosphate Hydrolase Deficiency, Hemolytic Anemia Due To AR 266120
X-Linked Anemia Without Thromobocytopenia XL 300835
Xerocytosis Gardos AD 616689
Xerocytosis, Hereditary AD 194380

Related Test

Name
PGxome®

Citations

  • Agarwal et al. 2016. PubMed ID: 27292444
  • Albuisson et al. 2013. PubMed ID: 23695678
  • An and Mohandas. 2008. PubMed ID: 18341630
  • Andolfo et al. 2013. PubMed ID: 23479567
  • Bolton-Maggs et al. 2012. PubMed ID: 22055020
  • Iolascon et al. 2013. PubMed ID: 23940284
  • Kim et al. 2017. PubMed ID: 28698843
  • Park et al. 2013. PubMed ID: 24086942
  • Park et al. 2016. PubMed ID: 26830532
  • Risinger et al. 2019. PubMed ID: 31030808
  • Wang et al. 2018. PubMed ID: 29572776

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

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