Galactosaemia is a rare inborn error of carbohydrate metabolism which is caused by the severe deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT). The GALT enzyme is the second enzyme in the Leloir biochemical pathway which converts galactose into glucose. This leads to an accumulation of the metabolites galactose-1- phosphate (Gal-1-P), galactitol, and galactonate (3). The incidents of Galactosaemia varies worldwide. It has a prevalence in western countries of between 16,000 and 60,000 live births (2).

Galactosaemia History

The first description of a baby with galactosaemia was over 100 years ago in 1908. In 1935 Mason and Turner were the first to report the successful use of a milk-free diet in an infant with galactosaemia (1). In the 1950s Luis Leloir identified the metabolic pathway in the metabolism of galactose (of which he won a Noble Prize for). In 1956 the GALT (galactose -1-phosphate uridyltransferase) was identified as the enzyme that is affected in classical galactosaemia and in 1988 the GALT gene was identified (2). 1988 was also the year when the Galactosaemia Support Group (GSG) was started by Sue and Andy Bevington when their son, with galactosamiea, was 9 months old.

Diagnosis

Galactosaemia usually presents within the first few weeks of life when the infant develops feeding difficulties, liver failure, E Coli sepsis and cataracts. Once galactose is removed from the diet then symptoms resolve. Unlike the UK, several countries have newborn screening for galactosaemia (USA, Netherlands, Ireland). Galactosaemia was considered for newborn screening in the UK in 2015 but turned down. The newborn screening committee felt that the evidenced showed that babies often present before the newborn screening result and screening and treatment did not prevent long term problems (5).

Long Term Problems in Galactosaemia

The GalNet registry was set up in 2014 and has been collecting outcome data internationally (2). The first published report last year reported that 85% of patients had brain impairments despite following the diet. Global development delay was documented in 52% of patients and 78% also showed a language delay. 52% of patients reported neurological complications including tremor (31%), general motor abnormality (clumsiness, co-ordination difficulties) (27%), ataxia (12%), seizures (8.1%) and dystonia (7.5%). Females suffer from fertility problems. Only 51.5% of females reported spontaneous puberty and 48.5% had a delayed or induced puberty. Primary ovarian insufficiency was reported in 79.7% in women.

Dietary Treatment

Dietary treatment is a galactose restricted diet. Lactose is the main source of galactose (a disaccharide comprising of glucose and galactose). Therefore, all mammalian milk and dairy products must be avoided (including breastmilk).

Infants

Once Galactosaemia is suspected in an infant then they should be changed onto a soy-based, casein hydrolysate or elemental formula (3). This will continue once a diagnosis is made. 

There is an ongoing debate into the safety of soy-based infant formulas due to concerns over its mild estrogenicity of soy. The Committee on Toxicology (COT) report in 2013 suggested that soy-based formulas should not be used unless in exceptional circumstances (9). In 2014 a review and meta-analysis demonstrated no effects on long-term growth, bone health and metabolic, reproductive, endocrine, immune and neurological functions, and neurocognitive parameters in non-galactosemic children treated with soy-based formulas (10). Elemental formulas are more expensive and there is no evidence to say they are any better for children with Galactosaemia than soy. Therefore, soya infant formula remains the formula of choice in the UK. 

Weaning

Weaning should begin at the usual age. As the diet avoids dairy products then there is a risk of nutrient deficiencies such as calcium and iodine. These nutrients are provided in the infant formula. When the amount of infant formula is reduced then food is relied upon for the minerals. Foods high in calcium should be encouraged in weaning to ensure a good calcium intake throughout life. Encouraging foods which are good sources of calcium including suitable hard cheese (see cheese section later), fortified plant-based yoghurts and foods fortified with calcium such as bread and breakfast cereals.

How strict should be diet be in Galactosaemia?

When babies are first diagnosed it is crucial to remove all the galactose in the diet to prevent liver damage and death. The UK for many years has recommended just a galactose/lactose restriction. A survey of international practice of adults with galactosaemia in 2015 found that 6 centres still restricted galactosides from fruit and vegetables and 12 centres restricted offal (6).

Fruit and vegetables

There is a small amount of free galactose in fruits, vegetables and legumes. The amount is negligible compared to the endogenous galactose production in humans and there no evidence to suggest any long-term problems (3). Therefore, the International Galactosaemia guidelines published in 2017 suggested fruit, vegetables and legumes should not be restricted (3). This is also supported by the first GalNet registry review (2019) which found people with a stricter diet (lactose restriction from fruit, vegetables as well as milk) developed neurological complications more frequently than those with a less strict diet (just a restriction of lactose from milk) (2).

Offal

Offal contains galactocerebrosides and gangliosides, but its galactose content is unknown. In the guidelines the opinion was divided whether to restrict offal (3). As the risk was theoretical it was put in the ‘in moderation’ section. In the UK we have not restricted offal for many years so this will not change practice.

Cheese

The guidelines allow cheese in the diet if the galactose content is <25mg/100g. In the UK the GSG has tested several kinds of cheese for galactose content and we now allow all UK vintage and extra mature cheddar, Emmental, Gruyere, Jarlsberg and Italian Parmesan / Grana Padano (11), (12).

Butter oil and Ghee

The GSG has also tested butter oil (also known as milk fat/anhydrous milk fat/butter fat) and Ghee and also found them to be negligible in galactose (13). If the only source of milk on the label comes from butter oil, butter fat or milk fat then it is suitable in galactosaemia. This includes products such as After Eight Mints and Jaffa Cakes.

Labelling

Since the allergy laws, it is now much easier to identify foods that are not allowed as all ingredients made from milk must be labelled ‘milk’ on all food labels. There are a couple of exceptions to look out for. The first being allowed cheese and butter oil / ghee as discussed above. The second is lactose free foods. These are dairy products labelled as ‘lactose free’ or ‘lacto free’. They are designed for people with lactose intolerance. Some lactose is removed and the remainder is enzymatically broken down into glucose and galactose. These products are still high in galactose and not suitable for people with galactosaemia. The third exception is the labelling of dairy foods. Current EU regulation states that foods direct from dairy are products in their own right e.g. yoghurt, cream, cheese and butter. Therefore, they do not have to be declared as milk on the label by law. Most manufacturers do follow best practice and declare these products as milk, but there have been occasions when they have not. Therefore, always check for the words yoghurt, cream, cheese and butter on the labels as well.

As galactosaemia is not an allergy to milk then we allow foods that do not contain milk but state on the label ‘may contain traces of milk’.

An infographic showing which bits of the Galactosaemia diet to look out for by Dietitian's Life.

Adults – can we relax the diet?

There is an ongoing debate whether adults can relax the diet, but currently there is insufficient evidence to say it is safe (3). Short term studies have looked at intakes of up to 4000mg of galactose over 14 weeks which had no effect on Gal-1-P concentrations and no clinical manifestation was observed in this time frame (14).

There are also 2 published cased studies of patients who were off diet since the age of three. These patients ingested approximately 2500 and 9000 mg of galactose per day (cow’s milk contains 2400 mg galactose/100 ml) and clinical outcome and biochemical parameters were similar to those seen in treated adult patients (7) (8). More evidence and long term research is needed before recommendations can be made.

Bone Health

Patients with galactosaemia are at risk of calcium and vitamin D deficiency due to the avoidance of dairy. It is therefore important to regularly monitor nutrients associated with bone health. It is important to encourage good sources of calcium in the diet, ensuing soya or plant based milks which are fortified with calcium and encouraging the use of allowed cheese. If requirements cannot be met by diet then a calcium supplement should be prescribed. Vitamin D is needed for calcium absorption and should be monitored. Vitamin D supplements should be prescribed for those at risk of deficiency (3).

Iodine

As cow’s milk is one of the main sources of iodine then people with galactosaemia are also at risk of iodine deficiency. Encouraging patients to include other sources of iodine rich foods such as eggs and whitefish in their diet and to choose a plant based milk that is fortified with iodine. If patients are unable to meet requirements from the diet, then an iodine supplement may be needed.

In Conclusion

Galactosaemia is a rare inherited metabolic disorder of galactose metabolism. The removal of galactose from the diet resolves the acute liver disorder but does not prevent long term problems. Currently the low galactose diet is recommended for life, but more research is needed to see if the diet can be relaxed in adulthood. 

Disclaimer

This article was first published in the NHD Magazine Issue 152, March 2020.

This article is for information, please speak to your metabolic team for tailored nutritional advice.

Learn more about Galactosaemia over at the Galactosaemia Support Group.

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