Rare Gastroenterology News

Disease Profile

Anemia sideroblastic and spinocerebellar ataxia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

D64.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

ASAT; Sideroblastic anemia with spinocerebellar ataxia; Pagon Bird Detter syndrome;

Categories

Blood Diseases; Congenital and Genetic Diseases; Metabolic disorders;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 2802

Definition
X-linked sideroblastic anemia and ataxia (XLSA-A) is a rare syndromic, inherited form of sideroblastic anemia (see this term) characterized by mild to moderate anemia (with hypochromia and microcytosis) and early-onset, nonor slowly progressive spinocerebellar ataxia.

Epidemiology
The prevalence is unknown. Only 10 genetically confirmed patients have been reported to date.

Clinical description
XLSA-A usually presents before the age of 3 years. Anemia is usually asymptomatic. In males, spinocerebellar symptoms are apparent in childhood and can include delayed walking, predominantly truncal ataxia, dysmetria and dysdiadochokinesis. Dysarthria and intention tremor are sometimes present. Ataxia may improve over time, but in the fifth to sixth decade of life a slow deterioration of walking is noted. Upper motor neuron signs in the legs such as equivocal or extensor plantar responses, brisk deep tendon reflexes and unsustained ankle clonus are sometimes present. Strabismus, as well as mild learning disability and depression, have also been reported in some, but intellectual abilities are generally within the normal range. Hepatic and systemic iron overload does not occur. Females are clinically asymptomatic.

Etiology
XLSA-A is caused by mutations in the ABCB7 gene (Xq13.3), encoding a mitochondrial ATP-binding cassette (ABC) transporter protein, which plays a role in heme production and iron homeostasis. A mutation in this gene alters the availability of reduced iron and therefore disrupts heme biosynthesis. The ABCB7 gene is highly expressed in both the bone marrow and the cerebellum, which may explain ataxia.

Diagnostic methods
Diagnosis is based on the presence of characteristic neurological and blood test findings. Mild to moderate hypochromic, microcytic anemia is noted in all males and both whole blood total erythrocyte protoporphyrin (TEP) and zinc erythrocyte protoporphyrin (ZnEP) are elevated. Bone marrow examination demonstrates the presence of increased iron stores with ring sideroblasts and peripheral blood smear reveals Pappenheimer bodies. In the majority of cases magnetic resonance imaging (MRI) shows cerebellar atrophy/hypoplasia. Female carriers display hematological abnormalities. Molecular genetic testing identifies a ABCB7 gene mutation, confirming the diagnosis.

Differential diagnosis
The main differential diagnosis includes other forms/causes of ataxia that typically present before the age of 3 years such as ataxia-telangiectasia, infantile-onset spinocerebellar ataxia, congenital disorder of glycosylation, and cerebellar malformations (e.g. Dandy-Walker malformation) (see these terms). Ataxia with vitamin E deficiency, Friedreich ataxia, ataxia oculomotor apraxia type 1 and 2, and X linked sideroblastic anemia (see these terms), the most common form of congenital sideroblastic anemia (without ataxia), should also be excluded.

Antenatal diagnosis
Prenatal testing is possible in families with a known ABCB7 mutation.

Genetic counseling
XLSA-A is inherited in an X-linked recessive manner and genetic counseling is possible. Males who inherit the mutation from their mother will be affected while females who inherit the mutation from their father or mother will be carriers and are clinically asymptomatic.

Management and treatment
There is no cure for XLSA-A and treatment is symptomatic. Anemia does not require treatment. Early physical therapy may aid in the acquisition of gross motor skills. Ankle fixation orthoses and walkers may be required to aid with mobility. Weighted eating utensils promote independent skills in children. Speech therapy is recommended for those with dysarthria. Crutches or a wheelchair may be needed by some patients.

Prognosis
While prognosis information is limited due to very few existing reports, XLSA-A does not appear to have a significant impact on life expectancy. Quality of life, however, can be significantly affected.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Anemia
Low number of red blood cells or hemoglobin
0001903
Ataxia
0001251
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment

[ more ]

0002167
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
30%-79% of people have these symptoms
Global developmental delay
0001263
Hyperreflexia
Increased reflexes
0001347
5%-29% of people have these symptoms
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Muscular hypotonia
Low or weak muscle tone
0001252
Scoliosis
0002650
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Percent of people who have these symptoms is not available through HPO
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality

[ more ]

0001939
Babinski sign
0003487
Clonus
0002169
Dysarthria
Difficulty articulating speech
0001260
Dysdiadochokinesis
Difficulty performing quick and alternating movements
0002075
Dysmetria
Lack of coordination of movement
0001310
Hypochromic microcytic anemia
0004840
Intention tremor
0002080
Juvenile onset
Signs and symptoms begin before 15 years of age
0003621
Nonprogressive cerebellar ataxia
0002470
Sideroblastic anemia
0001924
X-linked recessive inheritance
0001419

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      In-Depth Information

      • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Anemia sideroblastic and spinocerebellar ataxia. Click on the link to view a sample search on this topic.