Paediatrics chapters
Galactosaemia
An inherited inability to handle galactose, the sugar released from milk lactose: how the newborn presents after milk feeds, the urine and enzyme tests, lifelong milk exclusion, and the long-term outlook.
- Classic galactosaemia is an autosomal recessive deficiency of galactose-1-phosphate uridyltransferase (GALT); galactose comes from the lactose in all milk, so trouble starts within days of milk feeds.
- The baby has vomiting, poor feeding, jaundice, hepatomegaly, hypoglycaemia, bleeding and renal tubular loss, then cataracts, and is prone to E. coli sepsis; urine shows reducing substances that are not glucose, and red cell GALT confirms it.
- Treatment is lifelong removal of milk and lactose (soy-based formula; breastfeeding is contraindicated); despite good diet, learning problems and ovarian failure in girls are common.
On this page
Overview
Galactosaemia is an inborn error of carbohydrate metabolism in which the body cannot convert galactose to glucose. Galactose makes up half of lactose, the sugar of all milk (breast milk and animal milk). An affected newborn looks well at birth and becomes ill after a few days of milk feeds, with liver, kidney, brain and eye damage. It is one of the few metabolic diseases that is treatable by diet, so early recognition saves lives.
Akbar names galactosaemia as the common metabolic disease linked with jaundice in early infancy.
Galactose metabolism and the enzyme defect
| Step | Enzyme | What it does |
|---|---|---|
| 1 | Lactase (gut) | Splits lactose into glucose and galactose |
| 2 | Galactokinase | Galactose to galactose-1-phosphate |
| 3 | Galactose-1-phosphate uridyltransferase (GALT) | Galactose-1-phosphate plus UDP-glucose gives UDP-galactose and glucose-1-phosphate |
| 4 | UDP-glucose 4-epimerase | Interconverts UDP-galactose and UDP-glucose |
Types
| Type | Enzyme | Severity |
|---|---|---|
| Classic galactosaemia | GALT | Commonest and most severe |
| Galactokinase deficiency | Galactokinase | Mild: cataracts only |
| Epimerase deficiency | UDP-glucose 4-epimerase | Rare |
- All forms are autosomal recessive; parents are healthy carriers and each further child has a 1 in 4 risk.
- A milder screening variant (Duarte variant) can also lower the measured enzyme activity.
Pathophysiology
- In GALT deficiency, galactose-1-phosphate builds up in cells and injures the liver, kidney tubules, brain and lens.
- Excess galactose is also turned into galactitol (dulcitol) by aldose reductase. Galactitol draws water into the lens and causes cataract; rarely it raises intracranial pressure.
- The illness depends on intake: features appear only while galactose is being eaten and improve quickly when it is removed.
"Milk makes the baby sick": a well baby who becomes ill a few days after starting milk, and improves on IV fluids, should make you think of galactosaemia.
Clinical features
Newborn presentation
After a few days of milk:
- Refusal of feeds, vomiting, poor weight gain.
- Jaundice and hepatomegaly; liver failure with bleeding (coagulation defect) and hypoglycaemia.
- Lethargy, irritability, convulsions.
- Renal tubular dysfunction: acidosis, glycosuria and aminoaciduria.
- Cataract (may be seen early as a central lens opacity on ophthalmoscopy).
- E. coli sepsis, which can be the first finding; untreated infants may die in the first week.
If milk is continued
Cirrhosis, dense cataracts (partial blindness), intellectual disability and kidney damage.
A newborn with E. coli sepsis plus jaundice and cataract has galactosaemia until proven otherwise. Treating the sepsis alone and restarting milk brings the illness back.
Differential diagnosis (Akbar)
- Neonatal sepsis (which may coexist).
- Congenital rubella (cataract, hepatitis).
- Hereditary fructose intolerance and urea cycle disorders (vomiting with liver dysfunction).
Investigations
| Test | Finding |
|---|---|
| Urine reducing substances | Positive while the baby is on milk |
| Urine dipstick glucose (glucose oxidase) | Negative, so the reducing sugar is not glucose |
| Red cell GALT activity | Very low or absent: confirms classic galactosaemia |
| DNA testing of the GALT gene | Confirms and helps predict outcome |
| Blood glucose | Low |
| Bilirubin, liver tests, clotting | Raised bilirubin, coagulopathy |
| Blood gases | Normal anion gap, hyperchloraemic metabolic acidosis (renal tubular loss) |
| Urine | Aminoaciduria, albuminuria; ketones |
| Blood culture | Often E. coli |
| Eye examination | Cataract |
- Akbar adds that a specific enzymatic test on the urine can prove the reducing sugar is galactose.
- Newborn screening measures total galactose and GALT activity. The result must come back quickly, because affected infants can die in the first week.
- Prenatal diagnosis is possible by measuring GALT activity.
Negative urine reducing substances do not exclude galactosaemia: the test turns negative if the baby is vomiting, on IV fluids or no longer taking milk.
Reducing substance positive, glucose oxidase negative in a jaundiced baby on milk is the classic urine clue. If a screen suggests galactosaemia and reducing substances are present, change to a lactose-less formula at once while confirmation is awaited (Nelson).
Management
- Stop all milk at once: breast milk, formula and animal milk.
- Feed a soy-based formula or another lactose-less formula.
- Breastfeeding is absolutely contraindicated in galactosaemia (both books).
- Treat sepsis with antibiotics, correct hypoglycaemia, and give supportive care for liver failure and bleeding.
- The diet is lifelong: avoid milk and all milk products, and read food labels for dried milk and other hidden lactose.
- Calcium supplements are advised because milk is excluded.
- Educate parents, and later the child, about the diet; offer genetic counselling.
With galactose removed, the biochemical and clinical abnormalities correct quickly, although a very sick infant may still die before treatment takes effect.
The two contraindications to breastfeeding that come up in exams are galactosaemia and (relatively) phenylketonuria. In PKU, breastfeeding can be partly kept alongside a special formula; in galactosaemia it must stop completely.
Complications and prognosis
| Problem | Comment |
|---|---|
| Cataracts | May need surgery; avoided by early diet |
| Cirrhosis | If milk continues |
| Learning difficulty, speech delay | Can occur even with a strict diet |
| Severe intellectual disability | In untreated or late-treated children |
| Premature ovarian failure in girls | Usual, despite treatment; irregular periods |
| Tremor and movement problems | Later life |
| Death | From sepsis or liver failure if not recognised |
- Liver, kidney and eye damage are mainly a problem of the first few years.
- With early diagnosis and good diet the outlook is near-normal life, but mild intellectual impairment may still develop.
Galactokinase deficiency
- Autosomal recessive; galactose and galactitol build up.
- The only major feature is cataract (rarely raised intracranial pressure). The baby is not acutely ill.
- Homozygotes usually develop cataracts after the neonatal period; carriers may get cataracts as adults.
A baby with isolated cataract and no liver disease or sepsis points to galactokinase deficiency, not classic GALT deficiency.
Causes of cataract in infancy (exam list)
- Galactosaemia and galactokinase deficiency.
- Congenital rubella.
- Hypoparathyroidism, hypothyroidism.
- Lowe syndrome.
Expect: the GALT enzyme and autosomal recessive inheritance; a newborn who deteriorates after a few days of milk with vomiting, jaundice, hepatomegaly, hypoglycaemia and cataract; the link with E. coli sepsis; urine reducing substances positive with negative glucose oxidase, and that a negative test does not exclude it; confirmation by red cell GALT activity; breastfeeding contraindicated and soy-based formula for life; galactokinase deficiency causing cataract only; learning problems and ovarian failure despite treatment; galactosaemia in the lists of neonatal jaundice, hepatomegaly and infant cataract.
Quick revision
- Classic galactosaemia = GALT deficiency, autosomal recessive.
- Galactose comes from lactose in all milk; illness starts days after milk feeds.
- Vomiting, jaundice, hepatomegaly, hypoglycaemia, bleeding, tubular acidosis, cataract.
- E. coli sepsis is a classic association.
- Urine: reducing substance positive, dipstick glucose negative; negative test does not exclude.
- Confirm with red cell GALT activity; newborn screening needs a fast result.
- Stop milk for life; soy-based formula; no breastfeeding; calcium supplements.
- Galactokinase deficiency: cataract only (galactitol).
- Despite diet: learning difficulty and ovarian failure in girls.
Written by The House Job from standard references (Basis of Paediatrics by Pervez Akbar; Nelson Essentials of Paediatrics).
FAQ
Why does a baby with galactosaemia become ill only after birth?
Symptoms depend on galactose intake. Once the baby starts taking lactose in milk, galactose-1-phosphate builds up and illness follows within days.
Can the mother keep breastfeeding if the baby has galactosaemia?
No. Breast milk contains lactose, so breastfeeding must stop and a soy-based or lactose-less formula is used for life.
Why is the urine dipstick for glucose negative when reducing substances are positive?
The dipstick uses glucose oxidase, which reacts only with glucose. The reducing sugar in galactosaemia is galactose, so the dipstick stays negative while the reducing test is positive.
Does a strict diet guarantee a normal outcome?
No. Early diet prevents liver failure, cataracts and death, but many children still have learning difficulties and most girls develop ovarian failure.