Because the iron is essentially stuck in
the mitochondria, your child’s body cannot incorporate it into hemoglobin,
which red blood cells need to transport oxygen efficiently throughout the body.
This defect in red blood cell production also can alter the iron balance within
your child, often resulting in total body iron overload.
Sideroblastic anemia can be either
congenital (inherited) or acquired (not inherited). Both types have very
different causes, treatments, and prognoses. This page is primarily focused on
congenital sideroblastic anemia.
Dana-Farber/Boston Children's is an
international leader in the diagnosis and management of rare disorders of iron
metabolism. Through our Rare
Anemia and Iron Disorders Program children and families with rare iron
disorders have access to world-renown multidisciplinary teams of hematologists,
pathologists, and researchers.
The sideroblastic anemias can be divided
into congenital (inherited) forms and acquired forms. Acquired sideroblastic
anemias (SAs) are more common and are seen almost exclusively in older adults.
They usually are the result of acquired (not inherited) genetic mutations that
occur only in the red blood cell
precursors that lead to ringed sideroblasts. This form of sideroblastic anemia
– refractory anemia with ringed sideroblasts (RARS) – is classified within a
broader group of diseases called myelodysplastic
syndromes (MDS) and can eventually lead to leukemia. In more than 75% of
cases of RARS, the bone marrow cells have acquired a mutation in one particular
gene called SF3B1. Acquired sideroblastic anemias can also be due
to nutritional deficiencies, acquired metabolic diseases, or toxins.
By contrast, the congenital sideroblastic
anemias (CSAs) are inherited diseases caused by genetic mutations that are
present at birth in all the cells. Importantly, even though the mutations are inherited
and present at birth, anemia may not be present in infancy, and sometimes may
not be recognized until adulthood. Thus, it is particularly important to
distinguish late-onset CSA from an acquired SA because they have very different
causes, treatments, and prognoses.
The CSAs are the result of inborn abnormalities
in one of three pathways that occur in mitochondria: heme biosynthesis, the
synthesis of other iron containing compounds called iron sulfur clusters, and protein
synthesis in general within mitochondria. Approximately two-thirds of patients
with congenital sideroblastic anemias have inherited mutations in a known gene.
However, the remainder do not yet have a genetic explanation and are a focus of
our research. CSAs can be passed on
in families in several different patterns including autosomal recessive, autosomal
dominant, X-linked, and mitochondrial inheritance.
The CSAs are generally divided into those that affect only the blood
system (non-syndromic) and those that also affect other tissues, such as the
nervous system and muscles (syndromic). In some cases of syndromic
sideroblastic anemia, the anemia may be an incidental problem – the major signs
and symptoms of the disease may be in other tissues. In general, the CSAs that
affect heme synthesis result in non-syndromic anemia with small red blood cells
(microcytosis), whereas those that affect mitochondrial protein synthesis are
syndromic and have large red blood cells (macrocytosis). Mutations in genes
involved in iron-sulfur cluster synthesis generally have normal sized red blood
cells (normocytic) and may be syndromic or non-syndromic.
recognized forms of CSA with the genes that cause them are described below:
The symptoms and signs of congenital sideroblastic
anemia (CSA) in children are primarily related to the anemia and its severity:
Some forms of CSA are associated with other symptoms or signs outside
the blood system. These combinations of symptoms and signs are referred to as
syndromic CSAs. The associated symptoms can include:
The recognition of the specific CSA
diagnosis relies on an experienced clinician recognizing the characteristics of
the anemia (e.g., red blood cell size: microcytic, normocytic, or macrocytic),
the age of child (or adult) when symptoms are first noticed, and other potential
symptoms (such as muscle weakness).
CSAs are usually diagnosed with:
After all tests are completed, the hematologist will be able to outline
the best treatment options.
Treatment for CSA depends on the exact
type and severity of the disorder. Depending on the specific type of a child’s CSA,
a hematologist may recommend a variety of different treatments, including:
Stem cell transplant
Right now, the only cure for some CSAs is a stem cell transplant– the transplantation of normal blood stem cells from another person
(‘donor’) to your child. In CSA, the best transplant outcomes are almost always
when the donor is a healthy sibling with compatible stem cells. The stem cells replace
the diseased stem cells and restore normal blood production. In the syndromic
sideroblastic anemias, disease manifestations unrelated to the bone marrow
disease do not get better after bone marrow transplantation.
stem cell transplant also carries risk, it is recommended that patients with a
compatible full-sibling donor meet with our pediatric
stem cell doctors to learn more
about the process. Dana-Farber/Boston Children's has one of the largest pediatric stem cell transplant programs in the United States. Our Stem
Cell Transplant Center is at the
forefront of new, improved protocols for stem cell transplantation for
blood-related disorders, including CSA.
Scientists at Boston Children’s Hospital and Dana-Farber/Boston
Children’s Cancer and Blood Disorders Center are the international leaders in
research into the molecular underpinnings and identification of different
sub-types of CSA. Our researchers have made key discoveries of the specific
gene mutations and proteins involved in both syndromic and non-syndromic congenital
sideroblastic anemias, and we have an open research protocol that is helping us
to reach our ultimate goal of understanding the genetic basis of all types of
By building this scientific knowledge into the variability of CSAs, we
are better able to identify potential therapeutic options for each sub-type of
the disease. Some day we may be able to offer treatment options that directly
impact the genetic causes of CSA to cure the disease.
Research Study for Patients with CSA
If you, your child, or other family members have the key features of
congenital sideroblastic anemia, we invite you to contact us for an evaluation
or to learn more about our research. We have an open research protocol that is
helping to build our understanding of the key features and genetic
underpinnings of CSA. Through this protocol, children and adults who choose to
participate will agree to provide blood and urine samples. Our researchers will
then use those samples to assess the blood cells, iron proteins and to conduct
genetic testing that will sequence all the known CSA genes. This testing is
being performed primarily to increase scientific knowledge. However, if an
individual’s test reveals information that could be of clinical benefit, those results
will be returned to you and your doctor so that they can be
confirmed in a certified diagnostic laboratory – as long as you
indicate an interest in the results when signing up for the study.
To learn more about the study, contact Mark
D. Fleming, MD, DPhil at
Our Published CSA Research
The long-term outlook for children with CSA
depends heavily on the specific type of CSA. A child with CSA will need regular follow-up care by a hematologist.