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Disease Profile

Classic 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

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ICD-10

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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)

Galactose-1-phosphate uridyltransferase deficiency; Galactosemia type 1; GALT deficiency;

Summary

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

Orpha Number: 79239

Definition
A life-threatening metabolic disease with onset in the neonatal period. Infants usually develop feeding difficulties, lethargy, and severe liver disease.

Epidemiology
Global prevalence is unknown but estimated annual incidence has been reported to be between 1/40,000 and 1/60,000 in Western countries. The disorder appears to be more common in the Caucasian population than in other ethnic groups but figures in other populations may be underestimated. Males and females are equally affected.

Clinical description
When ingesting breast milk or lactose-containing formula, infants develop feeding problems, failure to thrive, and signs of liver damage (jaundice, bleeding tendency, hypoglycemia). In the absence of appropriate treatment (galactose restriction), sepsis (E-coli) and neonatal death may occur. Despite adequate treatment, long-term complications appear including cognitive impairments, motor deficits, ovarian dysfunction with reduced fertility in women and diminished bone density. Male fertility has not yet been thoroughly studied.

Etiology
Classic galactosemia is caused by mutations in the GALT (9p13) gene encoding the galactose-1-phosphate uridyltransferase enzyme. Mutations that severely impair enzyme activity result in the classic galactosemia phenotype. The so-called variants are mutations associated with higher residual enzyme activity resulting in milder or no features of galactosemia such as the Duarte variant (GALT gene mutation).

Diagnostic methods
In many countries, infants are routinely screened for galactosemia at birth. When neonatal screening is not performed, diagnosis is based on the clinical picture. Diagnosis can be confirmed by assay of the relevant metabolites, enzyme activity and GALT gene mutational analysis.

Differential diagnosis
Differential diagnoses include galactose epimerase deficiency and other diseases causing acute liver disease in the neonate.

Antenatal diagnosis
Prenatal testing is usually performed via gene mutation analysis by chorionic villus sampling. In at-risk relatives, testing is also possible to search for the mutation when already identified in a family.

Genetic counseling
Galactosemia follows an autosomal recessive pattern of inheritance. Parents of an affected child have a 25% chance of having affected children in subsequent pregnancies.

Management and treatment
Treatment is based primarily on galactose restriction in the diet. Infants should be fed with soy formula or other lactose-free formula. Patients are advised to follow a lifelong diet. To prevent a diminished bone mass, calcium, vitamin D and vitamin K supplements are recommended if dietary intake does not meet the recommended daily allowance. Monitoring of cognitive and motor development, gonadal function and bone mass is mandatory. Eye examinations are recommended in case of neonatal cataracts or in case of poor dietary compliance. Despite dietary treatment long-term complications occur.

Prognosis
Prognosis is dependent on age of diagnosis, disease severity and compliance with dietary restrictions, which affects the onset and course of secondary complications.

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
Abnormal bleeding
Bleeding tendency
0001892
Abnormality of the ovary
Abnormality of the ovaries
0000137
Hepatic failure
Liver failure
0001399
Hypoglycemia
Low blood sugar
0001943
Jaundice
Yellow skin
Yellowing of the skin

[ more ]

0000952
Osteoporosis
0000939
Weight loss
0001824
30%-79% of people have these symptoms
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Decreased fertility in females
Reduced fertility in females
0000868
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Impairment of galactose metabolism
0004915
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Nausea and vomiting
0002017
Speech apraxia
0011098
Speech articulation difficulties
0009088
5%-29% of people have these symptoms
Ataxia
0001251
Dysarthria
Difficulty articulating speech
0001260
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Lethargy
0001254
Neonatal death
Neonatal lethal
0003811
Sepsis
Infection in blood stream
0100806
Tremor
0001337
Percent of people who have these symptoms is not available through HPO
Albuminuria
0012592
Aminoaciduria
High urine amino acid levels
Increased levels of animo acids in urine

[ more ]

0003355
Autosomal recessive inheritance
0000007
Cirrhosis
Scar tissue replaces healthy tissue in the liver
0001394
Decreased liver function
Liver dysfunction
0001410
Diarrhea
Watery stool
0002014
Galactosuria
Increased urinary galactose level
0012023
Hyperchloremic metabolic acidosis
0004918
Hypergalactosemia
0012024
Hypergonadotropic hypogonadism
0000815
Increased level of galactitol in plasma
0410061
Increased level of galactitol in red blood cells
0410064
Increased level of galactitol in urine
0410062
Increased level of galactonate in red blood cells
0410063
Metabolic acidosis
0001942
Premature ovarian insufficiency
Early menopause
Premature menopause
Premature ovarian failure

[ more ]

0008209
Vomiting
Throwing up
0002013

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.

Newborn Screening

  • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
  • An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.

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 Classic galactosemia. This website is maintained by the National Library of Medicine.
  • The Merck Manual provides information on this condition for patients and caregivers.
  • 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

  • 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.