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Disease Profile

Galactosemia

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.

Unknown

Age of onset

Infancy

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ICD-10

E74.2

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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Categories

Congenital and Genetic Diseases; Newborn Screening

Summary

Galactosemia, which means “galactose in the blood,” refers to a group of inherited disorders that impair the body's ability to process and produce energy from a sugar called galactose. When people with galactosemia injest foods or liquids containing galactose, undigested sugars build up in the blood. Galactose is present in many foods, including all dairy products (milk and anything made from milk), many baby formulas, and some fruits and vegetables.[1][2] The impaired ability to process galactose can be due to the deficiency of any of 3 enzymes, caused by mutations in different genes.[3] There are 3 main types of galactosemia which are distinguished based on their genetic causes, signs and symptoms, and severity:[1][3][4][5][6]

  • Classic galactosemia (type 1) the most common and severe type, caused by mutations in the GALT gene, and characterized by a complete deficiency of an enzyme called galactose-1-phosphate uridyl transferase (GALT). Early signs and symptoms include liver dysfunction, susceptibility to infections, failure to thrive, and cataracts. These can usually be prevented or improved by early diagnosis and treatment, but other progressive or long-term problems are common despite treatment. These include intellectual deficits, movement disorders, and premature ovarian failure (in females).
  • Galactokinase deficiency (type 2) caused by mutations in the GALK1 gene and characterized by a deficiency of the enzyme galactokinase 1. This type typically causes only the development of cataracts, which may be prevented or resolved with treatment. Rarely, this type causes pseudotumor cerebri (a condition which mimics the symptoms of a large brain tumor when no brain tumor is present).
  • Galactose epimerase deficiency (type 3) caused by mutations in the GALE gene and characterized by a deficiency of the enzyme UDP-galactose-4-epimerase. Symptoms and severity of this type depend on whether the deficiency is confined to certain types of blood cells or is present in all tissues. Some people with this type have no signs or symptoms, while others have symptoms similar to those with classic galactosemia. Like in classic galactosemia, many symptoms can be prevented or improved with treatment.

There is also a "variant" of classic galactosemia called Duarte variant galactosemia, in which a person has mutations in the GALT gene but has only partial deficiency of the enzyme. Infants with this form may have jaundice, which resolves when switched to a low-galactose formula. Some studies have found that people with this form are at increased risk for mild neurodevelopmental problems, but other studies have found there is no increased risk. The risk may depend on the extent of the deficiency.[3][7]

Inheritance of all types of galactosemia is autosomal recessive.[1][3] The diagnosis may be suspected based on symptoms or results of newborn screening tests, and can be confirmed by measuring enzyme activity and genetic testing.[3] Depending on the type of galactosemia, treatment may involve removing galactose from the diet (as soon as the disorder is suspected), calcium supplementation, and individualized care for any additional symptoms.[6] The long-term outlook for people with galactosemia varies depending on the type, symptoms present, and commitment to the diet.[6]

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
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Failure to thrive in infancy
Faltering weight in infancy
Weight faltering in infancy

[ more ]

0001531
Feeding difficulties in infancy
0008872
Global developmental delay
0001263
Hepatic failure
Liver failure
0001399
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Jaundice
Yellow skin
Yellowing of the skin

[ more ]

0000952
Lethargy
0001254
Nausea and vomiting
0002017
Osteoporosis
0000939
30%-79% of people have these symptoms
Abnormality of coagulation
0001928
Abnormality of the voice
Voice abnormality
0001608
Ascites
Accumulation of fluid in the abdomen
0001541
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth

[ more ]

0001510
Hepatomegaly
Enlarged liver
0002240
Muscular hypotonia
Low or weak muscle tone
0001252
Pedal edema
Fluid accumulation in lower limbs
Lower leg swelling

[ more ]

0010741
Sepsis
Infection in blood stream
0100806
Tremor
0001337
5%-29% of people have these symptoms
Ataxia
0001251
Dysarthria
Difficulty articulating speech
0001260
Hemolytic anemia
0001878
Hypoglycemia
Low blood sugar
0001943
Hypogonadotropic hypogonadism
0000044
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Renal insufficiency
Renal failure
Renal failure in adulthood

[ more ]

0000083
Seizure
0001250
Speech apraxia
0011098
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505

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.

    Newborn Screening

    • The Newborn Screening Coding and Terminology Guide has information on the standard codes used for newborn screening tests. Using these standards helps compare data across different laboratories. This resource was created by the National Library of Medicine.

      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.

        Where to Start

        • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
        • Genetics Home Reference (GHR) contains information on Galactosemia. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
        • The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.

          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.
            Classic Galactosemia and Clinical Variant Galactosemia
            Epimerase deficiency galactosemia
            Duarte Variant Galactosemia
          • 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.
          • 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 Galactosemia. Click on the link to view a sample search on this topic.

            References

            1. Galactosemia. Genetics Home Reference. August, 2015; https://www.ghr.nlm.nih.gov/condition=galactosemia.
            2. Galactokinase deficiency. Baby's First Test. https://www.babysfirsttest.org/newborn-screening/conditions/galactokinase-deficiency. Accessed 10/9/2018.
            3. Sutton VR. Galactosemia: Clinical features and diagnosis. UpToDate. Waltham, MA: UpToDate; July 18, 2018; https://www.uptodate.com/contents/galactosemia-clinical-features-and-diagnosis.
            4. Pseudotumor Cerebri Information Page. National Institute of Neurological Disorders and Stroke (NINDS). June 20, 2018; https://www.ninds.nih.gov/Disorders/All-Disorders/Pseudotumor-Cerebri-Information-Page.
            5. Fridovich-Keil J, Bean L, He M, Schroer R. Epimerase Deficiency Galactosemia. GeneReviews. June 16, 2016; https://www.ncbi.nlm.nih.gov/books/NBK51671/.
            6. Sutton VR. Galactosemia: Management and outcome. UpToDate. Waltham, MA: UpToDate; March 13, 2017; https://www.uptodate.com/contents/galactosemia-management-and-outcome.
            7. Fridovich-Keil J, Gambello MJ, Singh RH, Sharer JD. Duarte Variant Galactosemia. GeneReviews. December 4, 2014; https://www.ncbi.nlm.nih.gov/books/NBK258640/.