Galactosaemia

Galactosaemia is a rare genetic metabolic disorder that impairs an individual's ability to metabolise the sugar galactose properly. The term is derived from Greek, meaning "galactose in the blood." It follows an autosomal recessive inheritance pattern, leading to a deficiency in very important enzymes necessary for galactose degradation.

Signs & Symptoms

Adults

In adults, symptoms can include speech delays, learning disabilities, behavioural issues, ataxia, tremors, and hormone deficiencies.

Infants

Infants are typically asymptomatic at birth, but symptoms emerge upon ingestion of galactose through breast or formula feeding. These symptoms include poor feeding and weight gain, vomiting, diarrhoea, hepatocellular damage, lethargy, and hypotonia. Progression of the condition may lead to sepsis, cataracts, and pseudotumor cerebri.

Children

Untreated galactosaemia in children can result in cataracts, developmental delays, intellectual disabilities, speech difficulties, motor skill difficulties, kidney disease, liver failure, sepsis, and premature ovarian insufficiency. Even with treatment, children may continue to experience various long-term complications.

Cause

Lactose in food is broken down by lactase into glucose and galactose. In individuals with galactosaemia, enzymes like galactokinase and galactose-1-phosphate uridyltransferase are deficient or absent, causing toxic levels of galactose or galactose-1-phosphate to accumulate. This accumulation leads to severe complications like hepatomegaly, cirrhosis, kidney failure, cataracts, seizures, hypoglycaemia, lethargy, brain damage, and ovarian failure. The condition is inherited in an autosomal recessive manner.

Mechanisms of Accumulation

Reduction to Galactitol

Accumulated galactose is reduced to galactitol by the enzyme aldose reductase. Galactitol is not further metabolised and accumulates in tissues, contributing to the toxic effects of galactosaemia.

Oxidation to Galactonate

Galactose can also be oxidised to galactonate, which may then enter the pentose phosphate pathway. This alternative pathway is less harmful compared to galactitol accumulation.

Diagnosis

Newborn screening (NBS) is commonly used to diagnose galactosaemia, allowing for early detection. If a family history of galactosaemia exists, prenatal tests like amniocentesis or chorionic villus sampling can be performed. The Beutler's test and Hill test are used in NBS to detect enzyme levels indicative of galactosaemia.

Types

Three types of galactosaemia are associated with deficiencies in different enzymes of the Leloir pathway:

1. Classic Galactosaemia (Type 1): Deficiency in galactose-1-phosphate uridyltransferase.
2. Galactokinase Deficiency (Type 2): Deficiency in galactokinase.
3. Galactose Epimerase Deficiency (Type 3): Deficiency in UDP galactose epimerase.

Treatment

The primary treatment for classic galactosaemia is the elimination of lactose and galactose from the diet, including the exclusion of dairy products. While this dietary restriction resolves acute complications, it does not prevent long-term complications affecting the brain and female gonads. Long-term complications may include speech difficulties, learning disabilities, neurological impairments, and ovarian failure. Infants with classic galactosaemia cannot be breast-fed and are usually fed a soy-based formula.

It is very important to differentiate between galactosaemia and lactose intolerance. Lactose intolerance results from a lactase deficiency and causes abdominal pains without long-term effects. In contrast, galactosaemia can lead to severe complications if galactose is ingested.

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Self-assessment MCQs (single best answer)

What is the inheritance pattern of galactosaemia?

Which enzyme deficiency is associated with Type 1 galactosaemia?

What is the primary treatment for classic galactosaemia?

Which of the following symptoms is NOT typically associated with untreated galactosaemia in children?

Galactose is broken down into which two simpler sugars?

Which enzyme converts accumulated galactose to galactitol?

What prenatal tests can be used to diagnose galactosaemia?

Which of the following is a long-term complication of galactosaemia despite dietary treatment?

Which symptoms are common in infants with galactosaemia after ingestion of galactose?

What differentiates galactosaemia from lactose intolerance?