Pregnancy in women with classical galactosaemia

Only a subtle and clinically insignificant increase of galactose metabolites occurs during pregnancy [52, 53] so no additional treatment is required during pregnancy for women with classical galactosaemia. Postpartum there is a transient increase in red blood cell metabolite concentrations and renal metabolite excretion. Normal healthy infant outcome is reported in the few pregnancies documented. A small number of women have successfully breast fed their infants with no adverse effect [52].

In the UK a lactose free diet only is advocated. Lactose is cleaved into its two components, glucose and galactose, when digested and it is the main dietary source of galactose. Cow’s milk contains 4.5–5.5% lactose, i.e. about 23 g of galactose per litre. All milk, milk products and manufactured foods containing milk need to be avoided. Lactose and galactose in milk based foods are shown in Table 18.3 and Table 18.4. Constituents of milk are also likely to be found in foods such as biscuits, some sweets and tinned and processed meats (Table 18.5). Many spreads (including reduced fat) and mayonnaise include milk components to improve their flavour. The lactose content of whey derivatives such as whey powder is high, comprising 70% of total solids. In contrast, the lactose content of casein is low, with the Casein and Caseinates Regulations [66] stating the maximum anhydrous lactose content of casein should not exceed 1% by weight [67]. Butter oil and ghee contain only minimal lactose, but the recommendation is to avoid these.

^* Data analysed by UK Galactosaemia Support Group.

Lactose powder is added to a diverse range of food products including bakery goods, confectionery, dry mixes, dried vegetables and crisps. It is often added to prepared foods to prevent caking or as a coating. It may be used in bakery goods for enhancing browning and, as it has one-sixth the sweetness of sucrose, it is added instead of sucrose to reduce the sweetness. It is commonly used as a filler and flowing agent in seasoning mixes for foods such as instant pot noodles. It may act as a carrier for flavours and seasonings and may be added to ham, bacon and salami. It may also be added to some artificial table top or tablet sweeteners.

Non milk derivatives that may be added to food products are shown in Table 18.6. These do not need to be avoided with the exception of lactitol, a polyol made from galactose. Some residual galactose is left after its fermentation in the gut so it is unsuitable in galactosaemia.

Lactitol does not contain lactose but may contain some galactose and should be avoided.

Galactosides

The α-galactosides are part of the oligosaccharides (raffinose, stachyose and verbacose) and are a potential source of galactose. They are found in foods such as peas, beans, lentils, cocoa, nuts, wheat, oat flour and vegetables [68] (Table 18.7).

Studies investigating the effects of galactosides in galactosaemia are rare, include limited numbers of subjects, are short term and inconclusive. The α-galactosidase linkage in oligosaccharides is not hydrolysable by the human small intestinal mucosa in vitro or in vivo [69]. Instead, the galactosides are rapidly degraded and fermented by the caecal microflora to produce volatile short chain fatty acids. Galactoside avoidance is not advocated in galactosaemia in the UK.

Galactose storage organs

Although meats do not contain significant amounts of carbohydrates, small amounts may be present in free form and bound to proteins as glycoproteins and galactolipids. Cell lipids and proteins continuously undergo degradation, releasing glycerol, fatty acids, amino acids and their carbohydrate components, including galactose [70]. Offal is a source of galactocerebrosides and gangliosides [3]. These are not avoided in galactosaemia in the UK.

Free and bound galactose

Free galactose has been reported in many fruits, vegetables and legumes [71] (Table 18.8). Free galactose content may vary from <0.1 mg/100 g to 40 mg/100 g [72, 73]. In selected plant materials, it ranges from 2 ± 0.1 mg/100 g in red potato to 39.7 mg/100 g in red pepper. Only kiwi fruit and red pepper have galactose contents >20 mg/100 g. Different seasons, variety and storage affect the free galactose content [73]. Generally fruits and vegetables provide nutritional benefit yet induce only a small increase in daily galactose intake (30–54 mg galactose/day) and their intake is not associated with poorer outcome in galactosaemia. In one study, one patient was given a synthetic diet containing <8 mg/day galactose and then challenged with 200 mg/day galactose for 3 weeks. This had little effect on concentrations of metabolic markers [74].

^* Unpublished. Data analysed by UK Galactosaemia Support Group.

^† [40, 41].

Bound galactose is also present in many plant foods as β-1-4-linked galactosyl residues in chloroplast membranes of green plant tissue. Gums and fibres (carrageenan, locust bean gum, tragacanth gum) are common sources of bound galactose. Whilst mice with galactosaemia are able to hydrolyse bound galactose in mouse chow (the hydrolysis of the bound galactose resulting in excretion of significant amounts of galactose and its metabolites in their urine [75]), in humans there is no evidence that excluding bound galactose is beneficial.

Overall, there are few data to suggest that avoiding galactose from any plant and non milk animal source is helpful. In the UK since 1983, only milk and milk products have been avoided [76] and long term outcome is not dissimilar to other countries where there are more complex and restrictive dietary management guidelines [14].

Other alternative infant formulas include low lactose formulas and casein hydrolysate formulas (Table 18.9). Medium chain triglyceride (MCT) based casein hydrolysate infant formula, such as Pregestimil Lipil, may be advantageous when there is significant liver disease and should be administered until this complication has resolved [3].

However, all low lactose and protein hydrolysate formulas based on cow’s milk protein will undoubtedly contain some residual lactose and the amounts vary. Manufacturers of these formulas declare their lactose content at <10 mg/100 kcal (420 kJ) as defined by the European Food Safety Authority (EFSA) [81]. A 5 kg infant taking 200 mL/kg of formula would have <10 mg/kg/day (or 50 mg/day) of galactose from this source. However, it is estimated that endogenous galactose production is likely to be at its highest in infancy (calculated at 41 mg/kg body weight/day) [59], so it is probably better to use a formula which contains no source of lactose.

Whey hydrolysate formulas are likely to contain a higher concentration of residual lactose and Pepti-Junior, for example, is likely to contain 100 mg/100 mL of lactose (personal communication) and are unsuitable. Enteral feeds for older children based on whey hydrolysates are unsuitable.

Any formula based on hydrolysed meat and soya should be free of lactose and suitable to use.

Amino acid based formula

This alternative is a suitable lactose free formula and is used by some centres as the first choice in babies with galactosaemia [14]. There have been at least three case reports of infants with galactosaemia given elemental (amino acid based) infant formulas successfully [82, 83] and they may offer an advantage as they are more likely than soya infant formulas to be fortified with novel nutrients such as long chain polyunsaturated fatty acids. The main challenge when using elemental formulas is to ensure infants establish a taste for soya based foods during the weaning period.

Vegetable based milks for children over 1 year of age

A number of commercial nutritionally enriched plant, cereal and nut based drinks (e.g. soya, oat, rice, hazelnut and almond) can be purchased in supermarkets, specialist shops or on the internet. Most of them contain approximately 120 mg/100 mL calcium and 0.8 µg/100 mL vitamin D. There are also nutritionally enriched follow on soya milks designed for children >1 year with added calcium, iron, vitamin D, some B vitamins and an energy profile similar to cow’s milk. Calcium absorption from soya drinks is similar to that from cow’s milk. Soya beverages made from soya protein isolate contain less free galactose (1.3 ± 0.2 mg/100 g) compared with whole soya beans (4.8–5.3 ± 1.7 mg/100 g) [73]. Rice milk contains traces of inorganic arsenic and it is recommended by the UK Food Standards Agency that children aged between 1 and 4½ years should avoid rice milk.

Unsafe milks

Since lactose is the carbohydrate source in animal milks, e.g. goat’s and sheep’s milks, these are unsuitable. A low lactose dairy drink, Lactofree (Arla), where about half the lactose is removed by filtration and the remainder is removed enzymatically, is available internationally. However, recent analysis has demonstrated that it contains a significant quantity of galactose, rendering it unsuitable for galactosaemia (Table 18.3) [84]. Lactase enzyme drops, which reduce the lactose content of cow’s milk, are also unsuitable.

Hard mature cheeses

A small number of hard mature cheeses are allowed. Most cheese types have high levels of casein (which contains no more than 1% lactose) and low levels of whey (which contains 70% lactose). The lactose content is reduced during the cheese making process: by removal of whey by drainage (during this stage approximately 98% will be removed); type of starter culture and coagulating enzyme can have an effect as can the acid produced – all influence the properties of the curd and the degree of whey expulsion. For harder cheeses the curd is cut into small cubes, which allows fluid to drain from the individual pieces of curd. Any residual lactose in cheese curd is metabolisd during its ripening [85] and, generally, the longer the cheese has matured the lower its lactose content.

In the UK, the following cheeses are allowed: Emmental, Gruyere, Jarlsberg, Parmigiano Reggiano and Grana Padano Italian Parmesans with an EU PDO (Protected Designation of Origin) seal on the label; also West Country Farmhouse mature Cheddar cheese with an EU PDO seal on the label. All of these cheeses have been extensively tested for their lactose and galactose content [86] and have been shown to contain minimal lactose and galactose on repeated analysis. Information regarding suitable West Country Farmhouse mature Cheddar cheese is available from www.farmhousecheesemakers.com. A PDO seal only guarantees that a food genuinely originates from a region and is produced to a specified quality; it does not indicate that it contains minimal lactose. Many food stuffs carry the PDO seal, e.g. other types of cheese, sausages, hams and regional breads, and these are not necessarily lactose free. However, the PDO seal should always be on the label of any West Country Farmhouse Cheddar cheese or Parmigiano Reggiano and Grana Padano Italian Parmesans to indicate their suitability.

All other cheeses are not permitted. Specific analysis has been commissioned by the UK Galactosaemia Medical Advisory Panel to test Gouda, Edam and some soft and processed cheeses, but all contain lactose and galactose; Mini Emmental Baby Bel contains a mean of 6–7 mg/100 g lactose and so is also unsuitable. The latter cheese is only fermented for 196 days and is usually on the retail market by 32 weeks of age [87].

Enzyme treated cheese products

A Lactofree Cheddar type of cheese has been produced from Lactofree (Arla) milk. Initial findings suggest this is low in lactose and galactose [84], but as there has been only limited analysis it is considered unsuitable in the galactosaemia diet.

Inclusion of cheese in the diet

There are different guidelines in different countries on the inclusion of cheese in the diet for galactosaemia. A survey of European practices [88] found that hard cheese such as Emmental and Gruyere were allowed in 63% of countries. Gouda was allowed in some countries but not others. In Australia and New Zealand some mature Cheddar cheese made by traditional methods are allowed [89]. In the USA some clinics allow mature hard cheese, e.g. Emmental, Gruyere, Tilsider [78].

Acceptability of low lactose/low galactose cheese

For many patients and carers the allowance of low lactose, but milk derived, cheese is a difficult concept to comprehend. However, a recent survey conducted by the UK Galactosaemia Support Group indicated there was a wide acceptance with 76% of patients eating one or more suitable types of cheese. The most preferred of the low lactose/low galactose cheeses were West Country Farmhouse Cheddar (70%), Emmental (31%), Italian Parmesan (24%), Gruyere (18%) and Jarlsberg (14%) [90].

Interpreting food labels

European ingredient listing rules [91–93] applied across the EU give clear guidance about food labelling of prepackaged foods that contain intentional milk, milk derivatives or lactose, which have to be clearly identified. Milk or lactose in carry-over additives or flavourings, and any other substances used as processing aids are also acknowledged. This only applies to prepackaged foods, e.g. canned and packet foods and alcoholic drinks, so foods sold loose (i.e. unpackaged), foods served in restaurants and certain fancy confectionery products are exempt.

However, the UK Foods Standards Agency (FSA) [94] has introduced The Provision of Allergen Information for Non Prepackaged foods – Voluntary Best Practice Guidance, targeted at food producers. It is requested that food suppliers communicate honestly with customers about the contents of any unpackaged foods that are sold; and that all employees receive training about food allegens (including milk), have up to date knowledge about the ingredient content of foods sold, consider cross-contamination and have an agreed practice for dealing with allergy information. The FSA has also launched a Chef Allergen card. The customer’s food allergy requirements are completed on a credit card which is handed to a chef who will then be able to decide if they are able to produce a lactose free meal for the individual. At the end of 2014, new UK legislation will be introduced that will require businesses to provide allergy information on food sold unpackaged in catering outlets, deli-counters, bakeries and sandwich bars.

Cross-contamination of manufactured foods with milk

Both milk free and milk containing foods may be manufactured in the same plant or even using the same machinery. Cross-contamination with milk is always possible and such foods may be voluntarily labelled may contain milk or milk products. It is likely that the quantity of milk that such a product would contain if cross-contaminated would be minute. The UK Galactosaemia Support Group Medical Advisory Panel permits foods that only carry a risk of cross-contamination with milk.