Galactosemia

Galactosemia is a rare genetic metabolic disorder which affects an individual's ability to properly metabolize the sugar galactose.

Goppert first described the disease in 1917, with its cause as a defect in galactose metabolism being identified by a group led by Herman Kalckar in 1956.

Its incidence is about 1 per 47,000 births (classic type). It is much rarer in Japan and much more common in Italy, specifically the traveler region.

Cause

Lactose in food (such as dairy products) is broken down by the body into glucose and galactose.In individuals with galactosemia, the enzymes needed for further metabolism of galactose are severely diminished or missing entirely, leading to toxic levels of galactose to build up in the blood, resulting in hepatomegaly (an enlarged liver), renal failure, cataracts, and brain damage. Without treatment, mortality in infants with galactosemia is about 75%.

Types

Galactose is converted into glucose by the action of three enzymes, known as the Leloir pathway. Accordingly, there are 3 known types of Galactosemia; type 1, 2 and 3:

Type	Diseases Database	OMIM	Gene	Locus	Enzyme	Name
Type 1	5056	230400	GALT	9p13	galactose-1-phosphate uridyl transferase	classic galactosemia
Type 2	29829	230200	GALK1	17q24	galactokinase	galactokinase deficiency
Type 3	29842	230350	GALE	1p36-p35	UDP galactose epimerase	galactose epimerase deficiency, UDP-Galactose-4-epimerase deficiency

The order of these three types is not the same as the order that the enzymes are encountered by galactose on its metabolic path (which is closer to GALK, GALT, and then GALE, though many variations can occur.)

Treatment

The only treatment for classic galactosemia is eliminating lactose and galactose from the diet. Even with an early diagnosis and a restricted diet, however, some individuals with galactosemia experience long-term complications such as speech difficulties, learning disabilities, neurological impairment (e.g. tremors, etc), and in girls, ovarian failure. These complications are treated if they appear in a manner similar to the way they would be treated in a non-galactosemic. Such complications have not been associated with Duarte galactosemia, and many individuals with Duarte galactosemia do not need to restrict their diet at all. Infants with classic galactosemia cannot be breast-fed due to lactose in human breast milk and are usually fed a soy-based formula.^[3]

Galactosemia is sometimes confused with lactose intolerance, but galactosemia is a more serious condition. Lactose intolerant individuals have an acquired or inherited shortage of the enzyme lactase, and experience abdominal pains after ingesting dairy products, but no long-term effects. In contrast, a galactosemic individual who consumes galactose can cause permanent damage to their bodies.

Long term complication of galactosemia includes:

• Speech deficits
• Ataxia
• Dysmetria
• Diminished bone density
• Premature ovarian failure
• Cataract

For a thorough scientific overview of galactosemia, one can consult chapter 72 of OMMBID. For more online resources and references, see inborn error of metabolism.