** Don't forget to click the drop down menu under this category for information on each individual type of Galactosemia

What is Galactosemia? Galactosemia is a disorder that affects how the body processes a simple sugar called galactose. A small amount of galactose is present in many foods. It is primarily part of a larger sugar called lactose, which is found in all dairy products and many baby formulas. The signs and symptoms of galactosemia result from an inability to use galactose to produce energy.

Researchers have identified several types of galactosemia. These conditions are each caused by mutations in a particular gene, and affect different enzymes involved in breaking down galactose.

Types of Galactosemia:
Classic galactosemia
Duarte  Galactosemia
Galactokinase Deficiency
Galactose Epimerase Deficiency
each causes different patterns of signs and symptoms, see the drop down menu for info on each category.

If infants with classic galactosemia are not treated promptly with a low-galactose diet, life-threatening complications appear within a few days after birth. Affected infants typically develop feeding difficulties, a lack of energy (lethargy), a failure to gain weight and grow as expected (failure to thrive), yellowing of the skin and whites of the eyes (jaundice), liver damage, and bleeding. Other serious complications of this condition can include overwhelming bacterial infections (sepsis) and shock. Affected children are also at increased risk of delayed development, clouding of the lens of the eye (cataract), speech difficulties, and intellectual disability. Females with classic galactosemia may experience reproductive problems caused by ovarian failure.

How common is galactosemia? Classic galactosemia occurs in 1 in 30,000 to 60,000 newborns. The other types are less common and sometimes range from fewer than 1 in 100,000 newborns.

What genes are related to galactosemia?Mutations in the GALE, GALK1, and GALT genes cause galactosemia.

The GALE, GALK1, and GALT genes provide instructions for making enzymes that are essential for processing galactose obtained from the diet. These enzymes break down galactose into another simple sugar, glucose, and other molecules that the body can store or use for energy.

Mutations in the GALT gene are responsible for classic galactosemia (type I). Most of these genetic changes almost completely eliminate the activity of the enzyme produced from the GALT gene, preventing the normal processing of galactose and resulting in the life-threatening signs and symptoms of this disorder. Another GALT gene mutation, known as the Duarte variant, reduces but does not eliminate the activity of the enzyme. People with the Duarte variant tend to have much milder features of galactosemia.

Galactosemia type II results from mutations in the GALK1 gene, while mutations in the GALE gene underlie galactosemia type III. Like the enzyme produced from the GALT gene, the enzymes made from the GALK1 and GALE genes play important roles in processing galactose. A shortage of any of these critical enzymes allows galactose and related compounds to build up to toxic levels in the body. The accumulation of these substances damages tissues and organs, leading to the characteristic features of galactosemia.

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.....but the chances of a baby having the only true allergy to human breastmilk or lactose in any form, called galactosemia, affects only 47 babies in the US per year... however, 150 people die annually from a falling coconut hitting them on the head. It's safe to say that this condition is insanely rare. 
                              --Christie Haskell
                      From "5 Breastfeeding Myths"


WHAT TO EXPECT AT BIRTH:
Galactosemia is one of the PKU (heel prick) test taken before you leave the hospital. At this time, the turn around time in each state various from 2-24 days before you find out the result. The states with the longest turn around seem to be Arkansas, New York, and Georgia as of 2013. Many other countries do not require or take this or other PKU life saving test. Visit the March of Dimes website for a complete list of PKU Diseases and more information on the complete newborn screening process- http://www.marchofdimes.com/baby/bringing-home-baby.aspx

Newborn Screening Lab Information
​www.cdc.gov/ncbddd/newbornscreening/


​Symptoms of Classic Galactosemia

The list of signs and symptoms mentioned in various sources for Classic Galactosemia includes the 11 symptoms listed below:

• Malnutrition
• Poor weight gain
• Failure to thrive
• Cirrhosis of the liver
• Enlarged liver
• Cataracts
• Mental retardation
• Neonatal death
• Vomiting
• Diarrhea
• Jaundice
• Malnutrition

In children who are homozygous for the classic galactosemia gene, signs are evident at birth or begin within a few days after milk ingestion, and include failure to thrive, vomiting, and diarrhea. Other clinical effects include liver damage (which causes jaundice, hepatomegaly, cirrhosis, and ascites), splenomegaly, galactosuria, proteinuria, and aminoaciduria. Cataracts may also be present at birth or develop later. Pseudotumor cerebri may occur.

Continued ingestion of galactose- or lactose-containing foods may cause mental retardation, malnourishment, progressive hepatic failure, and death — from the still-unknown process of galactose metabolites accumulating in body tissues. Although treatment may prevent mental impairment, galactosemia can produce a short attention span, difficulty with spatial and mathematical relationships, and apathetic, withdrawn behavior. Cataracts may be the only sign of galactokinase deficiency, resulting from the accumulation of galactitol, a metabolic by-product of galactose, in the lens. (2005, Professional Guide of Diseases)

Symptoms of Duarte Galactosemia

The symptoms are usually vomiting and jaundice. Our son started out on breastmilk and milk based formula. The vomiting started on day 2 of life for him. He was switched to a milk based lactose free formula soon after by the doctor. He continued to vomit several times a day while he remained on breastmilk and lactose free formula. By day 4 he was more jaundiced than usual. The doctor had us try him on several formulas (at this time we had not received the PKU test results). He was finally put on soy formula and the vomiting continued but wasn't as bad as before. Our son threw up about 6 times a day and it was entire bottles. He underwent a barium swallow test a week later and the test showed that he had stomach and small intestine ulcers. By day 17 the PKU test result came back, that he had duarte galactosemia. We were sent to Emory to have additional bloodwork done by Emory Genetics to verify the results. Those results took about 2 days and he tested positive for duarte galactosemia. He was immediately taken off of breastmilk and put on Enfamil Nutramigen Lipid (hypoallergenic) baby formula.

Clinical Information/Symptoms/Longterm Effects

Classic galactosemia (G/G).  Infants with classic galactosemia (G/G) have no GALT enzyme activity and are unable to oxidize galactose to CO2. Within days of ingesting breast milk or lactose-containing formulas,  affected infants develop life-threatening complications, including feeding problems, failure to thrive, hypoglycemia, hepatocellular damage, bleeding diathesis, jaundice, and hyperammonemia (see Table 2). If classic galactosemia is not treated, sepsis with Escherichia coli, shock, and death may occur. Infants who survive the neonatal period and who continue to drink milk that contains galactose develop mental retardation and other cortical and cerebellar tract signs.

Table 2. Frequency of Specific Findings in Symptomatic Neonates with Classic Galactosemia
Hepatocellular damage89%
Jaundice (74%) 
Hepatomegaly (43%) 
Abnormal liver function tests (10%) 
Coagulation disorders (9%) 
Ascites (4%)Food intolerance76%Vomiting (47%) 
Diarrhea (12%) 
Poor feeding (23%)Failure to thrive29%Lethargy16%Seizures1%Sepsis10%Escherichia coli (26 cases) 
Klebsiella (3) 
Enterobacter (2) 
Staphylococcus (1) 
Beta-streptococcus (1) 
Streptococcus faecalis (1)From a survey reporting findings in 270 symptomatic neonates [ Waggoner et al 1990)


If a lactose-/galactose-restricted diet is provided during the first three to ten days of life, the symptoms resolve quickly and prognosis is good for prevention of liver failure, Escherichia coli sepsis, neonatal death, and mental retardation. If the diagnosis of galactosemia is not established, the infant who is partially treated with intravenous antibiotics and self-restricted lactose intake demonstrates relapsing and episodic jaundice and bleeding from altered hemostasis concomitant with the introduction of lactose. If treatment is delayed, complications such as mental retardation and growth retardation are likely.

Even with early and adequate therapy, the long-term outcome in older children and adults with classic (G/G) galactosemia can include cataracts, speech defects, poor growth, poor intellectual function, neurologic deficits (predominantly extrapyramidal findings with ataxia), and ovarian failure [Schweitzer 2003). Outcome and the "disease burden" can be predicted based on the level of GALT enzyme activity, GALT genotype, age at which successful therapeutic control was achieved, and compliance with lactose restrictions. Formal outcome analysis for ovarian failure and for verbal dyspraxia found the 13CO2 breath test to be the most sensitive and specific prognostic parameter [Guerrero et al 2000, Webb et al 2003, Barbouth et al 2006).

The following details on long-term outcome were reported by Waggoner as the results of a retrospective, cross-sectional survey of 270 individuals with classic galactosemia.

• Mental development.  Of 177 individuals who were at least age six years and had no obvious medical causes for developmental delay other than galactosemia, 45% were described as developmentally delayed. The mean IQ scores of the individuals as a group declined slightly (4-7 points) with increasing age. Studies of Dutch individuals at various ages using a quality of life questionnaire indicated subnormal cognitive outcomes [Bosch, Grootenhuis et al 2004).
  
  
• Speech problems were reported in 56% (136/243) of individuals age three years or older.
  
  More than 90% of the individuals with speech problems were described as having delayed vocabulary and articulation problems, also called "verbal dyspraxia." The speech problem resolved in only 24%. A recent, more formal analysis found speech problems in 44% of individuals; 38% had a specific diagnosis of developmental verbal dyspraxia [Robertson & Singh 2000, Webb et al 2003).
  
  The developmental quotients and IQ scores observed in individuals with speech disorders as a group were significantly lower than those of individuals with normal speech; however, some individuals with speech problems tested in the average range.
  
  
• Motor function.  Among individuals older than age five years, 18% had fine-motor tremors and problems with coordination, gait, and balance. Severe ataxia was observed in two teenagers.
  
  
• Gonadal function.   Of 47 girls and women, 81% had signs of ovarian failure. Ovarian failure may be manifest as cutaneous rashes in estrogen-depleted children. The mean age at menarche was 14 years with a range from ten to 18 years. Eight out of 34 women over age 17 years (including two with "streak gonads") had primary amenorrhea. Most women developed oligomenorrhea and secondary amenorrhea within a few years of menarche. Only five out of 17 women over age 22 years had normal menstruation. Two, who gave birth at age 18 and 26 years, had never experienced normal menstrual periods.
  
  Guerrero et al (2000) determined that the development of primary ovarian failure in females with galactosemia is more likely if: (1) the individual's genotype is p.Gln188Arg/p.Gln188Arg, (2) the mean erythrocyte gal-1-P concentration is greater than 3.5 mg/dL during therapy, and (3) the recovery of 13CO2 from whole-body 13C-galactose oxidation is reduced below 5% of administered 13C-galactose.
  
  Normal serum concentrations of testosterone and/or follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were reported for males.
  
  
• Growth.  In many individuals, growth was severely delayed during childhood and early adolescence; when puberty was delayed and growth continued through the late teens, final adult heights were within the normal range. Decreased height over mean parental height was related to decreased IGF-I  Panis et al 2007].
  
  
• Cataracts were reported in 30% of 314 individuals. Nearly half the cataracts were described as "mild," "transient," or "neonatal" and resolved with dietary treatment; only eight were treated surgically. Dietary treatment had begun at a mean age of 77 days for those with cataracts compared to 20 days for those without cataracts. However, one of the eight individuals who required cataract surgery was an infant who had been treated from birth.
  
  
• Relationship between treatment and outcome.  No significant associations were found except for a greater incidence of developmental delay among individuals who were not treated until after age two months. However, IQ scores were not highly correlated with the age at which treatment began. The effect of early treatment on outcome was also studied in 27 sibships, three of which had three affected sibs. The older sibs had been diagnosed and treated after clinical symptoms occurred or newborn screening results had been reported, whereas the younger sibs had been treated within two days of birth. Although the younger sibs were treated early and only one developed neonatal symptoms, the differences in IQ scores among the sibs were not statistically significant, and the speech and ovarian function of the younger sibs were no better than those of their older sibs.
  
  Restriction of milk in the mother's diet during pregnancy was reported for 21 of the 38 infants who were treated from birth. The long-term outcome of these 21 was no better than that of the 17 individuals whose intake of mother's milk was not restricted during the pregnancy.
  
  No significant differences could be observed in the rate of complications between the individuals with residual enzyme activity and those with no measurable enzyme activity, except that individuals with some enzyme activity tended to be taller for their age.
  
  
• Individuals with/without neurologic complications.  No differences were observed in treatment or biochemical factors between the 56 individuals who had normal intellect, speech, and motor function and the 25 individuals who were developmentally delayed and had speech and motor problems.
  
  
• Relationships of complications.   Developmental delay and low IQ scores were associated with speech problems, motor problems, and delayed growth, but not with abnormal ovarian function.
  
  
• Gender differences.   Females had lower mean IQ scores after age ten years (p <0.05) and had lower mean heights for age at five to 12 years (p <0.05), but did not differ in frequency of speech or motor problems or in the treatment variables, including age treatment began, neonatal illness, or gal-1-P erythrocyte concentration. However, the association of problems with mental development, speech, and motor function could also indicate a specific neurologic abnormality in some cases of galactosemia.