Gaucher disease type 1: enzyme deficiency, inheritance and treatment

Cambridge University Hospitals describes Gaucher disease as a lysosomal storage disorder. Lysosomes are the recycling compartments inside cells, and in Gaucher disease the enzyme that should break down one of the products is not working effectively, so the material is stored. NICE names the missing enzyme as glucocerebrosidase and says the stored lipids create Gaucher cells in the liver, spleen, bone marrow and occasionally the lungs.

NICE explains there are three subtypes, of which type 1 (non-neuronopathic) is the most common, accounting for over 90% of people affected. The Gauchers Association says type 1 is sometimes misleadingly called adult Gaucher disease because people of all ages can be affected, and that it has a wide variation in signs, symptoms and course: many people have no symptoms and lead normal lives, though in some the disease can become life-threatening. In general, the later in life first symptoms appear, the less likely severe disease is.

The Gauchers Association says the most common sign is enlargement of the spleen or liver, which may be recognised in a child as young as 6 months and can distend the abdomen. An overactive spleen can lower red cells, white cells and platelets, causing anaemia, tiredness, infections and a tendency to nosebleeds and bruising.

Bones are often affected. Cambridge University Hospitals lists enlarged liver or spleen, bone pain, fatigue, increased risk of fracture, bleeding and infection. The Gauchers Association describes bone crises, sudden painful episodes from a lack of blood flow, thinner or deformed bones, and in more than half of people with type 1 a characteristic widening of the thigh bone above the knee on X-ray (the Erlenmeyer flask deformity).

• Enlarged spleen and liver, sometimes making the abdomen look swollen.

• Anaemia, low platelets and low white cells from an overactive spleen and affected marrow.

• Bone pain, bone crises, reduced bone density and fractures.

• Growth delay in children with severe disease.

Gaucher disease is autosomal recessive. Cambridge University Hospitals says a person needs two copies of the gene with the change, one from each parent, and that having one affected copy makes a person a carrier who is not affected. The Gauchers Association adds that the gene for glucocerebrosidase is on a non-sex chromosome, so males and females are affected equally.

The charity sets out the odds. If both parents are carriers, each pregnancy has a 25% chance of a child with Gaucher disease, a 50% chance of a carrier child and a 25% chance of a child who is neither. If one parent is a carrier and the other is not, none of the children will have the disease, but half are expected to be carriers. If one parent has the disease and the other is not a carrier, all children will be carriers. The odds for each pregnancy are independent of earlier children.

Carriers are more common in some groups. The Gauchers Association says approximately 1 in 10 people in the Ashkenazi population are carriers, and NICE gives the frequency of type 1 disease in people of Ashkenazi family origin as about 1 in 500 to 1 in 1,000 live births, compared with about 1 in 200,000 in non-Ashkenazi Europeans.

Cambridge University Hospitals says Gaucher-specific treatment is available as enzyme replacement therapy, an intravenous infusion usually given every one to two weeks, started in hospital and then given at home, or substrate reduction therapy, a daily tablet that slows production of the substances that build up. All medication is supplied to the home by a specialist homecare company. These treatments can only be received if you attend one of the UK national referral centres at least once a year for assessment and review.

NICE recorded in its eliglustat evaluation that clinical experts estimated 350 to 400 people with Gaucher disease of all types in England at the time.

Cambridge University Hospitals advises people to ask their doctor or specialist nurse about the effects and progression of the disease, to attend regular appointments with the lysosomal disorders team so they receive the most appropriate care and hear about new developments, and to consider contacting a patient support group. It reminds patients that if they are unwell outside clinic hours they should seek advice from their local healthcare team, and that an emergency doctor can ask the hospital for the metabolic consultant on call.

The Gauchers Association promotes awareness and research and provides support and information for people affected by Gaucher disease. Its pages cover the basis of the disease, the types, inheritance, and what to do after a diagnosis. For relatives, the practical point from the inheritance information is that brothers, sisters and children of a person with Gaucher disease may be carriers, and a genetics service can explain testing and what the results would mean for family planning.