An infant with galactosemia appears normal at birth, but within a few days or weeks loses his or her appetite (anorexia) 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 severe cases, overwhelming infection can cause life-threatening complications, but mild cases present few symptoms 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 usually show satisfactory general health and growth. They can make reasonable, though often not optimal, intellectual progress. 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, which is the best example of biochemical variant galactosemia subdivision. Significant debate exists in the medical literature as to whether individuals with Duarte variant galactosemia need to maintain a special diet.
Galactosemia is an autosomal recessive hereditary disorder caused by a deficiency of the enzyme galactose-1- phosphate uridyl transferase (GALT) that 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.
Recessive genetic diseases are determined by two genes, one received from the father and one from the mother. They occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one 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 defective 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 normal genes from both parents and be genetically normal for that particular trait is 25%.
Galactosemia occurs due to disruptions or changes (mutations) of the GALT gene. The abnormal accumulation of galactose-related chemicals in various organs of the body causes the signs and symptoms and physical findings of galactosemia.
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 GALT gene mutation.
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.
Infants and children with galactosemia should reduce galactose intake and have a diet that contains lactose-free milk substitutes and other foods such as soy bean products.
A lactose tolerance test should NOT be administered to galactosemic children. Fortunately the body of an infant with galactosemia can synthesize galactolipids and other essential galactose-containing compounds without the presence of galactose in food. Therefore, satisfactory physical development is possible if a strict diet is followed.
Speech therapy may be necessary for children with speech apraxia 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.
Appropriate treatment (i.e., antibiotic drugs) may be used to control infection. 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.
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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. Galactosemia. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:446.
Berry GT, Walter JH. Disorders of Galactose Metabolism. In: Saudubray JM, van den Berghe G, Walter JH, eds. Inborn Metabolic Diseases: Diagnosis and Treatment. 5th ed. Chap 7. New York, NY: Springer; 2012.
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 – 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.
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;35:1051–8. [PubMed: 22447152].
Waisbren SE, Potter NL, Gordon CM, Green RC, Greenstein P, Gubbels CS, Rubio-Gozalbo E, Schomer D, Welt C, Anastasoaie V, D’Anna 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; 35:279–86. [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].
Tang M, Wierenga K, Elsas LJ, Lai K. Molecular and biochemical characterization of human galactokinase and its small molecule inhibitors. Chem Biol Interact. 2010; 188:376–85. [PMC free article: PMC2980576] [PubMed: 20696150].
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; 83:248–50. [PMC free article: PMC1718484] [PubMed: 10952646].
Berry GT. Classic Galactosemia and Clinical Variant Galactosemia. 2000 Feb 4 [Updated 2014 Apr 3]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1518/ Accessed July16, 2015.
Fridovich-Keil J, Bean L, He M, Schroer R. Epimerase Deficiency Galactosemia. 2011 Jan 25 [updated 2013 Oct 24]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21290786 / Accessed July 22, 2015.
National Library of Medicine Genetics Home Reference. Galactosemia. Available at http://ghr.nlm.nih.gov/condition/galactosemia Reviewed January 2008. Accessed July 14, 2015.
Online Mendelian Inheritance in Man. Entry #230400 Galactosemia. Available at: http://www.omim.org/entry/230400. Accessed July 15, 2015.