Galactosemia commonly is due to deficiency of:
|A||Galactose- 1-phosphate uridyltransferase|
|B||Galactose- 1 -Phosphatase|
a. Galactosemia may be caused by inherited deficiency (defects) in Galactokinase, Galactose- 1- phosphate Uridyl transferase or uridine-Diphosphogalactose 4-Epimerase, though a deficiency in
Galactose-1 -phosphate uridyl transferase is the Best known.
b. In this, polyol (galactitol) →which accumulates causing cataract
a. Classic galactosemia is due to deficiency of galactose — 1-phosphate uridyl transferase (GALT) and
is typically associated with cataract formation, mental retardation and cirrhosis.
- 2nd one is due to galactokinase deficiency, leads primarily to cataract formation.
- 3rd one is due to UDP-galactose-4-epimerase deficiency — rarest type
b. In galactokinase deficiency → galactose accumulate in the blood and tissues → in the lens, galactose is
converted into galactitol by Aldose reductase →ed galactitol in lens → Hydration →cataract.
c. Both galactokinase and GALT deficiencies are transmitted as AR trait. GALT is a polymorphic enzyme and the
most common variant, called the DUARTE VARIANT has reduced activity. The M.C. mutation of the GALT gene
that causes classic galactosemia is the 0188R substitution (G).
d. C/F of classic galactosemia - of gal-1-PO4→in kid, liver and brain damage the organs]
i. Symptoms begin with in days to weeks after birth; the infant usually is resistant to ingest breast
ii. milk or, milk formulas, develops vomiting, shows poor nutrition and, fails to thrive.
iii. Jaundice, hepatomegaly, and evidence of liver disease may develop.
iv. Cataracts are usually not present at birth but develops gradually over weeks to months
v. MR becomes evident after 6 to 12 months and usually not reversible.
vi. Infants are subject to bacterial sepsis (especially Escherichia coli) and this may be the leading cause
e. Cirrhosis and MR are related to increased amounts of galactose- 1-phosphate in these tissues
f. Note that, the only consistent feature of galactokinase deficiency is cataract formation.
5. Treatment -
a. Removal of galactose from diet, especially milk
b. Milk substitutes such as Nutramigen are often used
c. galactose —free diet usually leads to a dramatic improvement in all C/F except for MR.
d. Pt should be kept on galactose free diet indefinitely or at least until they have attained adequate physical and neurological development.
[Note that →ed Hb A1ab level in blood of galactosemic pt due to non-enzymatic glycosylation
of Hb. In DM, there is ed 4Hb A1c]