Overview of the Condition

Galactosemia is an autosomal recessive disorder that poses fatal short-term and long-term complications (10). An autosomal recessive disorder occurs when two non-dominant mutated genes are be passed by two unaffected, carrier parents to their offspring (5). To be diagnosed with galactosemia, one of three hepatic enzymes that assist in the breakdown of galactose will be lacking; these being galactokinase (GALK), galactose -1-phosphate uridyltransferase (GALT), and UDP-galactose 4’ epimerase (GALE). The most common deficiency is the lack of GALT, the second step of the Leloir pathway, which according to Tyfield and Walter, occurs in 1/30,000 – 60,000 of live births. This is of large concern in the first few days of life because the immediate symptoms of galactosemia that occur are life threatening.

Symptoms include vomiting, diarrhea, poor appetite, urinary tract infections, hypotonia, cataracts, splenomegaly, encephalopathy, hepatomegaly, liver dysfunction, jaundice, failure to thrive, and death if treatment is delayed (7,5,2).

Treatment currently includes implementation of a lactose-restricted diet after diagnosis. Lactose is a disaccharide found in breast milk and milk-based formulas so to alleviate symptoms, infants are placed on a soy-based or an elemental formula to eliminate lactose and galactose (6).
Galactosemia is also characterized by long-term complications which include neurological dysfunction, cognitive impairment, decreased IQ, ovarian failure, delayed growth and decreased bone mineral density. There are many hypotheses that attempt to explain why long-term complications occur. Throughout life, endogenous production of galactose is released by glycoprotein and glycolipid degradation; some researchers attribute long-term complications to this fact. Other possible causes include exposure in utero to galactose from the mother’s lactose-containing diet or the galactose that is bound in some fruits and vegetables (3, 2,10). Some researchers have reason to believe there may be a connection to defective synthesis of the glycoproteins and glycolipids possibly due to the lack of galactose available to myelinate nerves; this would help to explain the neurological and cognitive function complications found in long-term patients (9,2,3). 

Metabolism and Regulation of Metabolism of Galactose

Carbohydrates are composed of linked monosaccharides, creating disaccharides, polysaccharides or oligosaccharides. Galactose is a monosaccharide which classifies it as a carbohydrate; when linked with glucose, lactose is formed. Because only polysaccharides begin to digest in the mouth and no carbohydrates digest in the stomach, lactose begins to break down in the small intestine. Pancreatic alpha-amylase is released to break other starches. Secretin raises the ph of the small intestine by the release of sodium bicarbonate; disaccharide specific enzymes on the brush border of the lumen, including maltase, isomaltase, sucrase and lactase, break down their specific disaccharide into glucose, fructose and galactose monosaccharides in the healthy individual. The hexose-shaped monosaccharides, glucose and galactose are nearly identical, the only difference being an extra oxygen molecule in the carbon four position on galactose. This difference poses the fatal problem in patients with galactosemia (6).

Normal galactose metabolism follows the Leloir pathway. Galactose is first phosphorylated by galactokinase to produce galactose-1-phosphate. Galactose -1-phosphate uridyltransferase swaps galactose with glucose in UDP-glucose which then releases glucose-1-phosphate; UDP-galactose 4’ epimerase creates UDP-glucose from UDP-galactose. Phosphoglucomutase then converts glucose-1-phosphate into glucose-6-phosphate, which can go through glycolysis to create glucose from glucose-6-phosphatase. Those with galactosemia lack one of the three major enzymes identified above to ultimately convert galactose into glucose. Classical galactosemia occurs most often which is a lack of galactose-1-phosphate uridyltransferase (GALT). With this enzyme lacking, there causes a buildup of galactose-1-phosphate (gal-1-P), galactitol and galactose, and therefore, the Leloir pathway cannot continue (2).

Diagnosis of Galactosemia


 During the first few days of life, a heel prick can test for classical galactosemia. Red blood cell (RBC) GALT enzyme activity will be near 0 mg/dl and RBC gal-1-P levels will be near 80 mg/dl if positive for the disorder. In a healthy patient, RBC GALT levels will be at 15.9 – 26.4 mg/dl and RBC gal-1-P levels will be at 0 mg/dl because there will not be a buildup of metabolites (2,1). Once placed on a lactose restricted diet, either with a soy-based or elemental formula, RBC gal-1-P levels are expected to be <5.1 mg/dl, optimally 2 – 5 mg/dl and 3 mg/dl by six months old (10,5,1).


Research Findings

Some studies have given results that show patient outcomes that contradict the current recommendations for a lactose restriction. Patients who have had liberalized diets for years have ended up having the same clinical outcome and long-term complications as those who have restricted lactose throughout their life (4,8).

Two studies have looked at the immediate effects of a lactose-free formula (elemental) versus a soy-based (still containing bound galactose from vegetables) on gal-1-P levels. The first was a retrospective case study with two infants diagnosed with classical galactosemia. After diagnosis, both patients were placed on a soy-based diet then moved to an elemental formula to remove all exogenous forms of galactose from soy because their gal-1-P levels were higher than the acceptable treatment levels of 2- 5 mg/dl. Both patients were placed on the elemental formula at four months old; their levels dropped to below 4 mg/dl and remained below 4 mg/dl for the remainder of the study (1). This suggested the galactose in soy does have a small effect on gal-1-P levels and eliminating all sources with an elemental formula is successful in reducing metabolite buildup.
The second study was also a retrospective case study, but only with one infant with classical galactosemia. Soy formula was introduced on day six, and then changed to an elemental formula at five months. Like the previous study, gal-1-P levels dramatically dropped with the elemental formula, however researchers commented that it is unrealistic to keep galactose levels at such a low level and still provide adequate nutrients, especially after infancy (10).

Researchers commented that it is unrealistic to keep galactose levels at such a low level and still provide adequate nutrients, especially after infancy.

Limitations are the same with both of these studies. Patients were only followed for the first two years of life and it is unknown if their gal-1-P levels would have tapered off naturally without altering diets. Also, there is no evidence to show if the lactose restriction is necessary past a certain age or when the benefits of lactose restriction start to taper off and begin to become detrimental.
A research study done in 2009 looked at sibling both having classical galactosemia. MRIs, cognitive IQ tests, speech and language development and neuroimaging was completed and compared in the children. The second born siblings were placed on a lactose restriction earlier than their older siblings and were therefore hypothesized to have a better long-term clinical outcome regarding all tests because of a quicker intervention. There was no difference noted between first and second born children; results showed second born subjects had worse, better and the same outcomes on all tests and images. 77% of patients showed speech and language problems, 71% had abnormal IQs, 23% had abnormal neurologic exams and none of the first born patients had normal MRIs. The most diet compliant family who had restricted lactose during the mother’s second pregnancy actually had the worst outcome showing the lowest IQ and worst brain myelination. Results of the study found no difference in the rate of complications with a galactose intake of either below or above 20 mg/d. Due to these findings, researchers suggest that liberalizing the diet after the first year and not restricting lactose during pregnancy may be beneficial (3).

Researchers suggest that liberalizing the diet after the first year and not restricting lactose during pregnancy may be beneficial.

1. Ficicioglu, C., Hussa, C., Yager, C., & Segal, S. (2008). Effect of galactose free formula on galactose-1-phosphate in two infants with classical galactosemia. European Journal of Pediatrics, 167, 595-596.

2. Fridovich-keil, J. (2006). Galactosemia: the good, the bad, and the unknown. Journal of Cellular Physiology, 209, 701-705.

3. Hughes, J., Ryan, S., Lambert, F., Geoghegan, O., Clark, A., Rogers, Y., Hendrof, U., Monavari, A., Twomey, E., & Treacy, E. (2009). Outcomes of siblings with classical galactosemia. The Journal of Pediatrics, 11, 721-726.

4. Lee, P., Lilburn, M., Wendel, U., & Schadewaldt P. (2003). A woman with untreated galactosaemia. Lancet, 362, 446.

5. Nelms, M., Sucher, K., & Long, S. (2007). Nutrition therapy and pathopysiology. Belmont: Thompson Brooks/Cole.

6. Rolfes, S., Pinna, K., & Whitney, E. (2006). Understanding normal and clinical nutrition. (7thed.). Belmont: Thomson Learning, Inc.

7. Rutherford, P., Davidson, D., & Matthai, S. (2002). Dietary calcium in galactosaemia. The British Dietetic Association, 15, 39-42.

8. Schadewaldt, P., Kamalanathan, L., Hammen, H., & Wendel, U. (2004). Age dependence of endogenous galactose formation in Q188R homozygous patients. Molecular Genetic Metabolism, 81, 31-44.

9. Tyfield L., Walter, J. (2002). Galactosemia. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill.

10. Zlatunich, C., & Packman, S. (2005). Galactosaemia: early treatment with an elemental formula. Journal of inherited metabolic disorders, 28, 163-168.


THE INFORMATION PROVIDED DOES NOT PROVIDE MEDICAL ADVICE. All content information is intended to be for general informational purposes only. Please see your doctor with regard to information attained from the above article if you are concerned with the health of your child. The content above is not a substitute for professional medical advice, diagnosis or treatment. NEVER NEGLECT YOUR DOCTOR’S PROFESSIONAL MEDICAL ADVICE BECAUSE OF SOMETHING YOU HAVE READ. 

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