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Last updated: December 14, 2016
Years published: 1987, 1990, 1991, 1995, 1999, 2005, 2007, 2015, 2019
NORD gratefully acknowledges the Galactosemia Foundation, Madeline Zupan, NORD Editorial Intern from the University of Notre Dame, and Gerard T. Berry, MD, Harvey Levy Chair in Metabolism, Director, Metabolism Program, Division of Genetics and Genomics, Boston Childrenโs Hospital and Professor of Pediatrics, Harvard Medical School, for assistance in the preparation of this report.
Galactosemia is a rare, hereditary disorder of carbohydrate metabolism that affects the bodyโs ability to convert galactose to glucose. Galactose is a sugar contained in milk, including human motherโs milk as well as other dairy products. It is also produced by the human body, and this is called endogenous galactose. Glucose is a different type of sugar. The disorder is caused by a deficiency of an enzyme galactose-1-phosphate uridylyl transferase (GALT) which is vital to this process. Early diagnosis and treatment with a lactose-restricted (dairy-free) diet is absolutely essential to avoid profound intellectual disability, liver failure and death in the newborn period. Galactosemia is inherited as an autosomal recessive genetic condition. Classic galactosemia and clinical variant galactosemia can both result in life-threatening health problems unless lactose is removed from the diet shortly after birth. A biochemical variant form of galactosemia termed Duarte is not thought to cause clinical disease due to lactose consumption.
An infant with galactosemia appears normal at birth, but within a few days or weeks loses their appetite and starts vomiting excessively. Yellowing of the skin, mucous membranes, and whites of the eyes (jaundice), enlargement of the liver (hepatomegaly), appearance of amino acids and protein in the urine, growth failure, and, ultimately, accumulation of fluid in the abdominal cavity (ascites) with abdominal swelling (edema) may also occur. Diarrhea, irritability, lethargy and a bacterial infection may also be early signs of galactosemia. In time, wasting of body tissues, marked weakness, and extreme weight loss occur unless lactose is removed from the diet.
Children with galactosemia who have not received early treatment may show arrested physical and mental development and are particularly susceptible to cataracts in infancy or childhood. In severely affected children, overwhelming infection in the newborn period can cause life-threatening complications, but children with Duarte variant galactosemia may have few signs and no serious impairment(s).
In order to avoid the consequences of galactosemia, which may include liver failure and kidney dysfunction, brain damage and/or cataracts, infants must be treated promptly by removing lactose from the diet. Children treated with this special diet may still experience complications. Speech and learning difficulties and some behavioral problems are still likely to occur. Ovarian impairment is almost always seen in girls with classic galactosemia and is associated with an increase in the blood level of the gonadotropin hormone, follicle-stimulating hormone (FSH); males with galactosemia do not usually exhibit abnormalities in gonadal function.
The above-mentioned complications associated with classic galactosemia and clinical variant galactosemia have not occurred in individuals with Duarte variant galactosemia, a type of biochemical variant galactosemia. However, in a minority of these children, developmental delay and/or a speech abnormality has occurred, but it is unclear whether this is related to accumulation of galactose and its metabolites. Individuals with Duarte variant galactosemia do not need to maintain a special diet.
Galactosemia occurs due to disruptions or changes (mutations) in the GALT gene resulting in deficiency of the GALT enzyme. This leads to abnormal accumulation of galactose-related chemicals in various organs of the body causes the signs and symptoms and physical findings of galactosemia.
The GALT enzyme is needed for the breakdown of the milk sugar, galactose. Deficiency of this enzyme results in the accumulation of toxic products: galactose-1-phosphate (a derivative of galactose) and galactitol (an alcohol derivative of galactose). Galactitol accumulates in the lens of the eye where it causes lens swelling and protein precipitation and subsequently, cataracts. Accumulation of galactose-1-phosphate is thought to cause the other signs and symptoms of disease.
Galactosemia is an autosomal recessive genetic disorder. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
Classic galactosemia is diagnosed in the range of 1/16,000 to 1/48,000 births through newborn screening programs around the world, depending on the diagnostic criteria used by the program. The disorder has been reported in all ethnic groups. An increased frequency of galactosemia occurs in individuals of Irish ancestry. Clinical variant galactosemia occurs most often in African Americans and native Africans in South Africa who have a specific
Classic galactosemia and clinical variant galactosemia are diagnosed when galactose-1-phosphate is elevated in red blood cells and GALT enzyme activity is reduced. Molecular genetic testing is also available to identify mutations in the GALT gene.
Nearly 100% of infants with galactosemia can be diagnosed in newborn screening programs using a blood sample from the heel stick. Infants with clinical variant galactosemia can be missed at newborn screening if GALT enzyme activity is not measured.
Treatment
Infants and children with galactosemia should have a lactose-restricted (dairy-free) diet that contains lactose-free milk substitutes and other foods such as soybean products.
A lactose tolerance test should NOT be administered to children with galactosemia. Fortunately, infants with galactosemia can synthesize galactolipids and other essential galactose-containing compounds without the presence of galactose in food. Therefore, satisfactory physical development is largely possible if a strict diet is followed.
Speech therapy may be necessary for children with childhood apraxia of speech or dysarthria. For school age children, individual education plans and/or professional help with learning skills may be necessary for some individuals, depending on psychological developmental assessments. Hormone replacement therapies may also be used in cases of delayed puberty and later in adolescence for the secondary loss of menstrual periods, termed premature ovarian insufficiency (POI).
Appropriate treatment (i.e., antibiotic drugs) may be used to control infection in the newborn period. The emotional effects of the strict diet may require attention and supportive measures throughout childhood.
Genetic counseling is recommended for families with children who have galactosemia.
Following several conferences, a consensus on the treatment and follow-up of patients with galactosemia was published in 2017.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact: www.centerwatch.com
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Fridovich-Keil JL, Walter JH. Galactosemia. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G, eds. The Online Metabolic and Molecular Bases of Inherited Disease (OMMBID). Chap 72. New York, NY: McGraw-Hill. 2015.
Berry GT, Walter JH, Fridovich-Keil JL. Disorders of Galactose Metabolism. In: Saudubray JM, van den Berghe G, Walter JH, eds. Inborn Metabolic Diseases: Diagnosis and Treatment. 6th ed. NewYork: Springer-Verlag Inc; 2016. p.139โ47.
Berry GT. Galactosemia. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:446.
JOURNAL ARTICLES
Rubio-Gozalbo ME, Haskovic M, Bosch AM, et al. The natural history of classic galactosemia: lessons from the GalNet registry. Orphanet Journal of Rare Diseases. 2019;14, 86. https://doi.org/10.1186/s13023-019-1047-z
Welling L, Bernstein LE, Berry GT, et al. International clinical guideline for the management of classical galactosemia: diagnosis, treatment, and follow-up. J Inherit Metab Dis. 2017 Mar;40(2):171-176. doi: 10.1007/s10545-016-9990-5. Epub 2016 Nov 17. https://pubmed.ncbi.nlm.nih.gov/27858262/
Pyhtila BM, Shaw KA, Neumann Se, Fridovich-Keil JL. Newborn screening for galactosemia in the United States: looking back, looking around, and looking ahead. JIMD Rep. 2015; 15:79-93. [PubMed: 24718839].
Timson, DJ. The molecular basis of galactosemia โ Past, present and future. Gene. 2015 Jul 2; Epub ahead of print. [PubMed: 26143117].
Lai K, Boxer MB, Marabotti A. GALK inhibitors for classic galactosemia. Future Med Chem. 2014 Jun; 6(9): 1003-15. [PubMed: 25068984].
Karadag N, Zenciroglu A, Eminoglu FT, Dilli D, Karagol BS, Kundak A, Dursun A, Hakan N, Okumus N. Literature review and outcome of classic galactosemia diagnosed in the neonatal period. Clin Lab. 2013; 59(9-10): 1139-46.
Potter NL, Nievergelt Y, Shriberg LD. Motor and speech disorders in classic galactosemia. JIMD Rep. 2013; 11:31โ41. [PMC free article: PMC3755563] [PubMed: 23546812].
Hoffmann B, Dragano N, Schweitzer-Krantz S. Living situation, occupation and health-related quality of life in adult patients with classic galactosemia. J Inherit Metab Dis. 2012;35:1051โ8. [PubMed: 22447152].
Waisbren SE, Potter NL, Gordon CM, Green RC, Greenstein P, Gubbels CS, Rubio-Gozalbo E, Schomer D, Welt C, Anastasoaie V, DโAnna K, Gentile J, Guo C-Y, Hecht L, Jackson R, Jansma BM, Li Y, Lip V, Miller DT, Murray M, Power L, Quinn N, Rohr F, Shen Y, Skinder-Meredith A, Timmers I, Tunick R, Wessel A, Wu B-L, Levy H, Elsas L, Berry GT. The adult galactosemic phenotype. J Inherit Metab Dis. 2012; 35:279โ86. [PMC free article: PMC3641771] [PubMed: 21779791].
Bosch AM. Classic galactosemia: dietary dilemmas. J Inherit Metab Dis. 2011 Apr; 43(2): 257-260. [PubMed: 20625932][PMC free article: 3063550].
Doyle CM, Channon S, Orlowska D, Lee PJ. The neuropsychological profile of galactosemia. J Inherit Metab Dis. 2010 Oct; 33(5): 603-9. [PubMed: 20607611].
Shield JP, Wadsworth EJ, MacDonald A, Stephenson A, Tyfield L, Holton JB, Marlow N. The relationship of genotype to cognitive outcome in galactosaemia. Arch Dis Child. 2000; 83:248โ50. [PMC free article: PMC1718484] [PubMed: 10952646].
INTERNET
Berry GT. Classic Galactosemia and Clinical Variant Galactosemia. 2000 Feb 4 [Updated 2021 Mar 11]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviewsยฎ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1518/ Accessed Jan 12, 2022.
Fridovich-Keil J, Bean L, He M, et al. Epimerase Deficiency Galactosemia. 2011 Jan 25 [Updated 2021 Mar 4]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviewsยฎ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK51671/ Accessed Jan 12, 2022.
Galactosemia. Medline Plus. National Library of Medicine. Reviewed 18 August 2020. Available at: https://ghr.nlm.nih.gov/condition/galactosemia Accessed Jan 12, 2022.
Galactosemia. Online Mendelian Inheritance in Man. Entry #230400. 05/14/2020. Available at: https://www.omim.org/entry/230400 Accessed Jan 12, 2022.
Galactosemia. Orphanet. Last update: December 2011. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=352 Accessed Jan 12, 2022.
Galactosemia Resource provides information and support for Duarte: https://duartegalactosemia.org/index.html Accessed Jan 12, 2022
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