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Pediatrics1513 papers

Congenital anemia

Last edited: 4/14/2026

Overview

Congenital anemia in the context of inborn errors of metabolism often arises from severe combined immunodeficiency (SCID) and other genetic disorders affecting hematopoiesis and metabolism, leading to significant clinical manifestations beyond anemia, including immunodeficiency and multi-organ dysfunction 1518.

Diagnosis

  • Clinical Presentation: Severe infections, neurodevelopmental delays, skin manifestations, hepatosplenomegaly, and hematological abnormalities including anemia 152025.
  • Laboratory Tests: Elevated methylmalonic acid and homocysteine levels, complete blood count (CBC) showing anemia and thrombocytopenia, lymphocyte subset analysis 3611.
  • Genetic Testing: Next-generation sequencing (NGS) panels for mutations in ADA, RAG1/2, CHD7, and other SCID-related genes 1118.
  • Immunological Assessment: Flow cytometry for T, B, and NK cell populations, functional immune assays 527.

    • Management

  • First-Line Treatments: Hematopoietic stem cell transplantation (HSCT) for SCID-related anemia 424.
  • Adjunctive Therapies:
    • - Carnitine Supplementation: For metabolic disorders affecting fatty acid oxidation 1417. - Vitamin Supplementation: Specific vitamins like cobalamin for disorders affecting cobalamin metabolism 632. - Calcineurin Inhibitors: Cyclosporin A for managing Omenn syndrome symptoms 2024.
  • Supportive Care: Antibiotic prophylaxis, immunoglobulin replacement therapy, and management of metabolic crises 710.

    • Special Populations

  • Pregnancy: Early diagnosis and management of metabolic disorders crucial; prenatal screening and counseling recommended 623.
  • Pediatrics: Newborn screening programs essential for early detection and intervention 31321.
  • Comorbidities: Consideration of multi-system involvement requiring multidisciplinary care 126.

    • Key Recommendations

  • Early Newborn Screening: Implement comprehensive newborn screening programs to identify metabolic disorders and SCID early 31321 (Evidence: Strong).
  • Hematopoietic Stem Cell Transplantation: Prioritize HSCT for definitive treatment of SCID-related congenital anemia 424 (Evidence: Strong).
  • Genetic Testing Utilization: Employ next-generation sequencing panels for accurate diagnosis of genetic causes of congenital anemia 1118 (Evidence: Moderate).
  • Supportive Metabolic Management: Provide carnitine and vitamin supplementation as indicated by specific metabolic defects 141732 (Evidence: Moderate).
  • Multidisciplinary Care: Ensure comprehensive care addressing immune deficiency, metabolic abnormalities, and potential complications 126 (Evidence: Expert opinion).

    • References

    1 Grunebaum E, Booth C, Cuvelier GDE, Loves R, Aiuti A, Kohn DB. Updated Management Guidelines for Adenosine Deaminase Deficiency. The journal of allergy and clinical immunology. In practice 2023. link 2 van de Burgt N, van Doesum W, Grevink M, van Niele S, de Koning T, Leibold N et al.. Psychiatric manifestations of inborn errors of metabolism: A systematic review. Neuroscience and biobehavioral reviews 2023. link 3 Schnabel E, Kölker S, Gleich F, Feyh P, Hörster F, Haas D et al.. Combined Newborn Screening Allows Comprehensive Identification also of Attenuated Phenotypes for Methylmalonic Acidurias and Homocystinuria. Nutrients 2023. link 4 Laberko A, Yukhacheva D, Rodina Y, Abramov D, Konovalov D, Radygina S et al.. BCG-Related Inflammatory Syndromes in Severe Combined Immunodeficiency After TCRαβ+/CD19+ Depleted HSCT. Journal of clinical immunology 2020. link 5 Cirillo E, Cancrini C, Azzari C, Martino S, Martire B, Pession A et al.. Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network. Frontiers in immunology 2019. link 6 Grandone E, Martinelli P, Villani M, Vecchione G, Fischetti L, Leccese A et al.. Prospective evaluation of pregnancy outcome in an Italian woman with late-onset combined homocystinuria and methylmalonic aciduria. BMC pregnancy and childbirth 2019. link 7 MacNeill EC, Walker CP. Inborn Errors of Metabolism in the Emergency Department (Undiagnosed and Management of the Known). Emergency medicine clinics of North America 2018. link 8 Evans N. Updated perinatal palliative standards emphasise choice and bereavement support. Nursing children and young people 2017. link 9 Aldubayan SH, Rodan LH, Berry GT, Levy HL. Acute Illness Protocol for Fatty Acid Oxidation and Carnitine Disorders. Pediatric emergency care 2017. link 10 Fletcher JM. Metabolic emergencies and the emergency physician. Journal of paediatrics and child health 2016. link 11 Pupavac M, Tian X, Chu J, Wang G, Feng Y, Chen S et al.. Added value of next generation gene panel analysis for patients with elevated methylmalonic acid and no clinical diagnosis following functional studies of vitamin B12 metabolism. Molecular genetics and metabolism 2016. link 12 Caglayan Sozmen S, Isik S, Arikan Ayyildiz Z, Yildiz K, Cakır Y, Ozer E et al.. Cyclosporin treatment improves skin findings in omenn syndrome. Pediatric dermatology 2015. link 13 Rose NC, Dolan SM. Newborn screening and the obstetrician. Obstetrics and gynecology 2012. link 14 Nasser M, Javaheri H, Fedorowicz Z, Noorani Z. Carnitine supplementation for inborn errors of metabolism. The Cochrane database of systematic reviews 2012. link 15 Sebnem Kilic S, Kavurt S, Balaban Adim S. Transfusion-associated graft-versus-host disease in severe combined immunodeficiency. Journal of investigational allergology & clinical immunology 2010. link 16 Bakare N, Menschik D, Tiernan R, Hua W, Martin D. Severe combined immunodeficiency (SCID) and rotavirus vaccination: reports to the Vaccine Adverse Events Reporting System (VAERS). Vaccine 2010. link 17 Nasser M, Javaheri H, Fedorowicz Z, Noorani Z. Carnitine supplementation for inborn errors of metabolism. The Cochrane database of systematic reviews 2009. link 18 Gennery AR, Slatter MA, Rice J, Hoefsloot LH, Barge D, McLean-Tooke A et al.. Mutations in CHD7 in patients with CHARGE syndrome cause T-B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome. Clinical and experimental immunology 2008. link 19 Shibata F, Toma T, Wada T, Inoue M, Tone Y, Ohta K et al.. Skin infiltration of CD56(bright) CD16(-) natural killer cells in a case of X-SCID with Omenn syndrome-like manifestations. European journal of haematology 2007. link 20 Rego S, Kemp A, Wong M, Knight P. Omenn syndrome: therapeutic effects of cyclosporin. Journal of paediatrics and child health 2006. link 21 Hasegawa LE, Au SM, Matsumoto CA. The obstetrician's role in newborn metabolic screening: a physician survey. Hawaii medical journal 2005. link 22 Gennery AR, Hodges E, Williams AP, Harris S, Villa A, Angus B et al.. Omenn's syndrome occurring in patients without mutations in recombination activating genes. Clinical immunology (Orlando, Fla.) 2005. link 23 Campbell ED, Ross LF. Incorporating newborn screening into prenatal care. American journal of obstetrics and gynecology 2004. link 24 Meyer-Bahlburg A, Haas JP, Haase R, Eschrich U, Wawer A, Frank L et al.. Treatment with cyclosporin A in a patient with Omenn's syndrome. Archives of disease in childhood 2002. link 25 Aladangady N, Kinmond S, Cant AJ, Gibson B, Coutts JA. A preterm baby with Omenn syndrome. European journal of pediatrics 2000. link 26 Boudny P, Kurrer MO, Stamm B, Laeng RH. Malakoplakia of the colon in an infant with severe combined immunodeficiency (SCID) and charge association. Pathology, research and practice 2000. link80031-X) 27 Wada T, Takei K, Kudo M, Shimura S, Kasahara Y, Koizumi S et al.. Characterization of immune function and analysis of RAG gene mutations in Omenn syndrome and related disorders. Clinical and experimental immunology 2000. link 28 Brooks EG, Filipovich AH, Padgett JW, Mamlock R, Goldblum RM. T-cell receptor analysis in Omenn's syndrome: evidence for defects in gene rearrangement and assembly. Blood 1999. link 29 Chilosi M, Facchetti F, Notarangelo LD, Romagnani S, Del Prete G, Almerigogna F et al.. CD30 cell expression and abnormal soluble CD30 serum accumulation in Omenn's syndrome: evidence for a T helper 2-mediated condition. European journal of immunology 1996. link 30 Dyke MP, Marlow N, Berry PJ. Omenn's disease. Archives of disease in childhood 1991. link 31 Yagi T, Dinh TM. Identification of the NADH-binding subunit of NADH-ubiquinone oxidoreductase of Paracoccus denitrificans. Biochemistry 1990. link 32 Bachmann C. Vitamins and inherited human errors of metabolism. International journal for vitamin and nutrition research. Supplement = Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Supplement 1989. link 33 Baybick JH. Reticuloendotheliosis with eosinophilia (Omenn's syndrome). Findings in fine needle aspirate of a lymph node. Acta cytologica 1987. link 34 Jouan H, Le Deist F, Nezelof C. Omenn's syndrome--pathologic arguments in favor of a graft versus host pathogenesis: a report of nine cases. Human pathology 1987. link80376-3) 35 Yagi T. Purification and characterization of NADH dehydrogenase complex from Paracoccus denitrificans. Archives of biochemistry and biophysics 1986. link90731-9) 36 Luhrs CA, Sadasivan E, da Costa M, Rothenberg SP. The isolation and properties of multiple forms of folate binding protein in cultured KB cells. Archives of biochemistry and biophysics 1986. link90705-8) 37 Mudd SH. Inborn errors of metabolism. Vitamin-responsive genetic disease. Journal of clinical pathology. Supplement (Royal College of Pathologists) 1974. link

    Original source

    1. [1]
      Updated Management Guidelines for Adenosine Deaminase Deficiency. — Grunebaum E, Booth C, Cuvelier GDE, Loves R, Aiuti A, Kohn DB The journal of allergy and clinical immunology. In practice (2023)
    2. [2]
      Psychiatric manifestations of inborn errors of metabolism: A systematic review. — van de Burgt N, van Doesum W, Grevink M, van Niele S, de Koning T, Leibold N et al. Neuroscience and biobehavioral reviews (2023)
    3. [3]
      Combined Newborn Screening Allows Comprehensive Identification also of Attenuated Phenotypes for Methylmalonic Acidurias and Homocystinuria. — Schnabel E, Kölker S, Gleich F, Feyh P, Hörster F, Haas D et al. Nutrients (2023)
    4. [4]
      BCG-Related Inflammatory Syndromes in Severe Combined Immunodeficiency After TCRαβ+/CD19+ Depleted HSCT. — Laberko A, Yukhacheva D, Rodina Y, Abramov D, Konovalov D, Radygina S et al. Journal of clinical immunology (2020)
    5. [5]
      Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network. — Cirillo E, Cancrini C, Azzari C, Martino S, Martire B, Pession A et al. Frontiers in immunology (2019)
    6. [6]
      Prospective evaluation of pregnancy outcome in an Italian woman with late-onset combined homocystinuria and methylmalonic aciduria. — Grandone E, Martinelli P, Villani M, Vecchione G, Fischetti L, Leccese A et al. BMC pregnancy and childbirth (2019)
    7. [7]
      Inborn Errors of Metabolism in the Emergency Department (Undiagnosed and Management of the Known). — MacNeill EC, Walker CP Emergency medicine clinics of North America (2018)
    8. [8]
      Updated perinatal palliative standards emphasise choice and bereavement support. — Evans N Nursing children and young people (2017)
    9. [9]
      Acute Illness Protocol for Fatty Acid Oxidation and Carnitine Disorders. — Aldubayan SH, Rodan LH, Berry GT, Levy HL Pediatric emergency care (2017)
    10. [10]
      Metabolic emergencies and the emergency physician. — Fletcher JM Journal of paediatrics and child health (2016)
    11. [11]
      Added value of next generation gene panel analysis for patients with elevated methylmalonic acid and no clinical diagnosis following functional studies of vitamin B12 metabolism. — Pupavac M, Tian X, Chu J, Wang G, Feng Y, Chen S et al. Molecular genetics and metabolism (2016)
    12. [12]
      Cyclosporin treatment improves skin findings in omenn syndrome. — Caglayan Sozmen S, Isik S, Arikan Ayyildiz Z, Yildiz K, Cakır Y, Ozer E et al. Pediatric dermatology (2015)
    13. [13]
      Newborn screening and the obstetrician. — Rose NC, Dolan SM Obstetrics and gynecology (2012)
    14. [14]
      Carnitine supplementation for inborn errors of metabolism. — Nasser M, Javaheri H, Fedorowicz Z, Noorani Z The Cochrane database of systematic reviews (2012)
    15. [15]
      Transfusion-associated graft-versus-host disease in severe combined immunodeficiency. — Sebnem Kilic S, Kavurt S, Balaban Adim S Journal of investigational allergology & clinical immunology (2010)
    16. [16]
      Severe combined immunodeficiency (SCID) and rotavirus vaccination: reports to the Vaccine Adverse Events Reporting System (VAERS). — Bakare N, Menschik D, Tiernan R, Hua W, Martin D Vaccine (2010)
    17. [17]
      Carnitine supplementation for inborn errors of metabolism. — Nasser M, Javaheri H, Fedorowicz Z, Noorani Z The Cochrane database of systematic reviews (2009)
    18. [18]
      Mutations in CHD7 in patients with CHARGE syndrome cause T-B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome. — Gennery AR, Slatter MA, Rice J, Hoefsloot LH, Barge D, McLean-Tooke A et al. Clinical and experimental immunology (2008)
    19. [19]
      Skin infiltration of CD56(bright) CD16(-) natural killer cells in a case of X-SCID with Omenn syndrome-like manifestations. — Shibata F, Toma T, Wada T, Inoue M, Tone Y, Ohta K et al. European journal of haematology (2007)
    20. [20]
      Omenn syndrome: therapeutic effects of cyclosporin. — Rego S, Kemp A, Wong M, Knight P Journal of paediatrics and child health (2006)
    21. [21]
      The obstetrician's role in newborn metabolic screening: a physician survey. — Hasegawa LE, Au SM, Matsumoto CA Hawaii medical journal (2005)
    22. [22]
      Omenn's syndrome occurring in patients without mutations in recombination activating genes. — Gennery AR, Hodges E, Williams AP, Harris S, Villa A, Angus B et al. Clinical immunology (Orlando, Fla.) (2005)
    23. [23]
      Incorporating newborn screening into prenatal care. — Campbell ED, Ross LF American journal of obstetrics and gynecology (2004)
    24. [24]
      Treatment with cyclosporin A in a patient with Omenn's syndrome. — Meyer-Bahlburg A, Haas JP, Haase R, Eschrich U, Wawer A, Frank L et al. Archives of disease in childhood (2002)
    25. [25]
      A preterm baby with Omenn syndrome. — Aladangady N, Kinmond S, Cant AJ, Gibson B, Coutts JA European journal of pediatrics (2000)
    26. [26]
      Malakoplakia of the colon in an infant with severe combined immunodeficiency (SCID) and charge association. — Boudny P, Kurrer MO, Stamm B, Laeng RH Pathology, research and practice (2000)
    27. [27]
      Characterization of immune function and analysis of RAG gene mutations in Omenn syndrome and related disorders. — Wada T, Takei K, Kudo M, Shimura S, Kasahara Y, Koizumi S et al. Clinical and experimental immunology (2000)
    28. [28]
      T-cell receptor analysis in Omenn's syndrome: evidence for defects in gene rearrangement and assembly. — Brooks EG, Filipovich AH, Padgett JW, Mamlock R, Goldblum RM Blood (1999)
    29. [29]
      CD30 cell expression and abnormal soluble CD30 serum accumulation in Omenn's syndrome: evidence for a T helper 2-mediated condition. — Chilosi M, Facchetti F, Notarangelo LD, Romagnani S, Del Prete G, Almerigogna F et al. European journal of immunology (1996)
    30. [30]
      Omenn's disease. — Dyke MP, Marlow N, Berry PJ Archives of disease in childhood (1991)
    31. [31]
      Identification of the NADH-binding subunit of NADH-ubiquinone oxidoreductase of Paracoccus denitrificans. — Yagi T, Dinh TM Biochemistry (1990)
    32. [32]
      Vitamins and inherited human errors of metabolism. — Bachmann C International journal for vitamin and nutrition research. Supplement = Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Supplement (1989)
    33. [33]
      Reticuloendotheliosis with eosinophilia (Omenn's syndrome). Findings in fine needle aspirate of a lymph node. — Baybick JH Acta cytologica (1987)
    34. [34]
      Omenn's syndrome--pathologic arguments in favor of a graft versus host pathogenesis: a report of nine cases. — Jouan H, Le Deist F, Nezelof C Human pathology (1987)
    35. [35]
      Purification and characterization of NADH dehydrogenase complex from Paracoccus denitrificans. — Yagi T Archives of biochemistry and biophysics (1986)
    36. [36]
      The isolation and properties of multiple forms of folate binding protein in cultured KB cells. — Luhrs CA, Sadasivan E, da Costa M, Rothenberg SP Archives of biochemistry and biophysics (1986)
    37. [37]
      Inborn errors of metabolism. Vitamin-responsive genetic disease. — Mudd SH Journal of clinical pathology. Supplement (Royal College of Pathologists) (1974)
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