A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD)

Daniel H. Wiseman*, Alison May, Stephen Jolles, Philip Connor, Colin Powell, Matthew M. Heeney, Patricia J. Giardina, Robert J. Klaassen, Pranesh Chakraborty, Michael T. Geraghty, Nathalie Major-Cook, Caroline Kannengiesser, Isabelle Thuret, Alexis A Thompson, Laura Marques, Stephen Hughes, Denise K. Bonney, Sylvia S. Bottomley, Mark D. Fleming, Robert F. Wynn

*Corresponding author for this work

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Congenital sideroblastic anemias (CSAs) are a heterogeneous group of inherited disorders identified by pathological erythroid precursors with perinuclear mitochondrial iron deposition in bone marrow. An international collaborative group of physicians and laboratory scientists collated clinical information on cases of CSA lacking known causative mutations, identifying a clinical subgroup of CSA associated with B immunodeficiency, periodic fevers, and development delay. Twelve cases from 10 families were identified. Median age at presentation was 2 months. Anemia at diagnosis was sideroblastic, typically severe (median hemoglobin, 7.1 g/dL) and markedly microcytic (median mean corpuscular volume, 62.0 fL). Clinical course involved recurrent febrile illness and gastrointestinal disturbance, lacking an infective cause. Investigation revealed B-cell lymphopenia (CD19+ range, 0.016-0.22 × 10 9/L) and panhypogammaglobulinemia in most cases. Children displayed developmental delay alongside variable neurodegeneration, seizures, cerebellar abnormalities, sensorineural deafness, and other multisystem features. Most required regular blood transfusion, iron chelation, and intravenous immunoglobulin replacement. Median survival was 48 months, with 7 deaths caused by cardiac or multiorgan failure. One child underwent bone marrow transplantation aged 9 months, with apparent cure of the hematologic and immunologic manifestations. We describe and define a novel CSA and B-cell immunodeficiency syndrome with additional features resembling a mitochondrial cytopathy. The molecular etiology is under investigation.

Original languageEnglish (US)
Pages (from-to)112-123
Number of pages12
JournalBlood
Volume122
Issue number1
DOIs
StatePublished - Jul 4 2013

Fingerprint

Bone
B-Lymphocytes
Fever
Iron
Cells
Intravenous Immunoglobulins
Chelation
Hemoglobins
Blood
Medical Laboratory Personnel
Lymphopenia
Erythrocyte Indices
Deafness
Bone Marrow Transplantation
Blood Transfusion
Anemia
Seizures
Bone Marrow
Physicians
Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Wiseman, D. H., May, A., Jolles, S., Connor, P., Powell, C., Heeney, M. M., ... Wynn, R. F. (2013). A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD). Blood, 122(1), 112-123. https://doi.org/10.1182/blood-2012-08-439083
Wiseman, Daniel H. ; May, Alison ; Jolles, Stephen ; Connor, Philip ; Powell, Colin ; Heeney, Matthew M. ; Giardina, Patricia J. ; Klaassen, Robert J. ; Chakraborty, Pranesh ; Geraghty, Michael T. ; Major-Cook, Nathalie ; Kannengiesser, Caroline ; Thuret, Isabelle ; Thompson, Alexis A ; Marques, Laura ; Hughes, Stephen ; Bonney, Denise K. ; Bottomley, Sylvia S. ; Fleming, Mark D. ; Wynn, Robert F. / A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD). In: Blood. 2013 ; Vol. 122, No. 1. pp. 112-123.
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abstract = "Congenital sideroblastic anemias (CSAs) are a heterogeneous group of inherited disorders identified by pathological erythroid precursors with perinuclear mitochondrial iron deposition in bone marrow. An international collaborative group of physicians and laboratory scientists collated clinical information on cases of CSA lacking known causative mutations, identifying a clinical subgroup of CSA associated with B immunodeficiency, periodic fevers, and development delay. Twelve cases from 10 families were identified. Median age at presentation was 2 months. Anemia at diagnosis was sideroblastic, typically severe (median hemoglobin, 7.1 g/dL) and markedly microcytic (median mean corpuscular volume, 62.0 fL). Clinical course involved recurrent febrile illness and gastrointestinal disturbance, lacking an infective cause. Investigation revealed B-cell lymphopenia (CD19+ range, 0.016-0.22 × 10 9/L) and panhypogammaglobulinemia in most cases. Children displayed developmental delay alongside variable neurodegeneration, seizures, cerebellar abnormalities, sensorineural deafness, and other multisystem features. Most required regular blood transfusion, iron chelation, and intravenous immunoglobulin replacement. Median survival was 48 months, with 7 deaths caused by cardiac or multiorgan failure. One child underwent bone marrow transplantation aged 9 months, with apparent cure of the hematologic and immunologic manifestations. We describe and define a novel CSA and B-cell immunodeficiency syndrome with additional features resembling a mitochondrial cytopathy. The molecular etiology is under investigation.",
author = "Wiseman, {Daniel H.} and Alison May and Stephen Jolles and Philip Connor and Colin Powell and Heeney, {Matthew M.} and Giardina, {Patricia J.} and Klaassen, {Robert J.} and Pranesh Chakraborty and Geraghty, {Michael T.} and Nathalie Major-Cook and Caroline Kannengiesser and Isabelle Thuret and Thompson, {Alexis A} and Laura Marques and Stephen Hughes and Bonney, {Denise K.} and Bottomley, {Sylvia S.} and Fleming, {Mark D.} and Wynn, {Robert F.}",
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Wiseman, DH, May, A, Jolles, S, Connor, P, Powell, C, Heeney, MM, Giardina, PJ, Klaassen, RJ, Chakraborty, P, Geraghty, MT, Major-Cook, N, Kannengiesser, C, Thuret, I, Thompson, AA, Marques, L, Hughes, S, Bonney, DK, Bottomley, SS, Fleming, MD & Wynn, RF 2013, 'A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD)', Blood, vol. 122, no. 1, pp. 112-123. https://doi.org/10.1182/blood-2012-08-439083

A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD). / Wiseman, Daniel H.; May, Alison; Jolles, Stephen; Connor, Philip; Powell, Colin; Heeney, Matthew M.; Giardina, Patricia J.; Klaassen, Robert J.; Chakraborty, Pranesh; Geraghty, Michael T.; Major-Cook, Nathalie; Kannengiesser, Caroline; Thuret, Isabelle; Thompson, Alexis A; Marques, Laura; Hughes, Stephen; Bonney, Denise K.; Bottomley, Sylvia S.; Fleming, Mark D.; Wynn, Robert F.

In: Blood, Vol. 122, No. 1, 04.07.2013, p. 112-123.

Research output: Contribution to journalArticle

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T1 - A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD)

AU - Wiseman, Daniel H.

AU - May, Alison

AU - Jolles, Stephen

AU - Connor, Philip

AU - Powell, Colin

AU - Heeney, Matthew M.

AU - Giardina, Patricia J.

AU - Klaassen, Robert J.

AU - Chakraborty, Pranesh

AU - Geraghty, Michael T.

AU - Major-Cook, Nathalie

AU - Kannengiesser, Caroline

AU - Thuret, Isabelle

AU - Thompson, Alexis A

AU - Marques, Laura

AU - Hughes, Stephen

AU - Bonney, Denise K.

AU - Bottomley, Sylvia S.

AU - Fleming, Mark D.

AU - Wynn, Robert F.

PY - 2013/7/4

Y1 - 2013/7/4

N2 - Congenital sideroblastic anemias (CSAs) are a heterogeneous group of inherited disorders identified by pathological erythroid precursors with perinuclear mitochondrial iron deposition in bone marrow. An international collaborative group of physicians and laboratory scientists collated clinical information on cases of CSA lacking known causative mutations, identifying a clinical subgroup of CSA associated with B immunodeficiency, periodic fevers, and development delay. Twelve cases from 10 families were identified. Median age at presentation was 2 months. Anemia at diagnosis was sideroblastic, typically severe (median hemoglobin, 7.1 g/dL) and markedly microcytic (median mean corpuscular volume, 62.0 fL). Clinical course involved recurrent febrile illness and gastrointestinal disturbance, lacking an infective cause. Investigation revealed B-cell lymphopenia (CD19+ range, 0.016-0.22 × 10 9/L) and panhypogammaglobulinemia in most cases. Children displayed developmental delay alongside variable neurodegeneration, seizures, cerebellar abnormalities, sensorineural deafness, and other multisystem features. Most required regular blood transfusion, iron chelation, and intravenous immunoglobulin replacement. Median survival was 48 months, with 7 deaths caused by cardiac or multiorgan failure. One child underwent bone marrow transplantation aged 9 months, with apparent cure of the hematologic and immunologic manifestations. We describe and define a novel CSA and B-cell immunodeficiency syndrome with additional features resembling a mitochondrial cytopathy. The molecular etiology is under investigation.

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