Introduction disease is an inherited, genetic disorder which results in the lack of an enzyme 'acid alpha-glucosidase. disease is also known as acid maltase deficiency or glycogen storage disease type II. To understand the implications of this it is useful to know a little about this enzymes normal activity. The human body contains many different types of cells. A basic cell has many components as you can see from the diagram below, including the nucleus which contains chromosomes. Within the cell there is a small compartment called the lysosome - this contains all the enzymes the cell needs to manage its recycling of waste products. The enzymes in the lysosome begin the process of breaking down glycogen but in disease this is ineffective. The glycogen accumulates in various types of muscle skeletal (eg limb, body & respiratory muscle), smooth (eg the muscles involved in feeding/swallowing) and cardiac (heart muscle predominantly in children). Inheritance Page 1
disease is an inherited genetic disorder described medically as an 'autosomal recessive disease. Each person has 23 pairs of chromosomes which contain genes they receive 1 set from each parent. Genes contain the necessary information to allow our body to be formed and to function. It is estimated that every human being has 8-10 genes that have changes within them (called mutations) however only some can cause disease. disease only produces symptoms when both copies of the gene are affected. This may well have occurred when both parents have 1 copy of the genetic mutation. They are said to be carriers (ie without any evidence of disease) but their offspring may inherit both copies of the faulty gene. There are other possibilities eg if 1 parent has disease and the other either has no mutation or is a carrier. In the former case all the children will be carriers and the latter there is a 50% chance of having an affected child and a 50% chance of a carrier. If you would like further information about the inheritance pattern in your personal circumstances or to know whether it is likely that any other members of your family are affected please discuss this with your physician or specialist nurse. Symptoms The signs and symptoms of disease are directly related to the muscles affected. The disease is progressive in nature, and affects proximal, respiratory and cardiac (infants) muscle. There are currently thought to be 2 main types of disease: Infantile Classic infantile is the most severe end of the spectrum with rapidly progressive cardiomegaly (enlarged heart) hepatomegaly (enlarged liver) weakness and hypotonia ('floppy ). This leads to early death usually in the first year of life Infantile variant has a slower progression and less severe cardiomegaly. It Page 2
usually presents during the first year of life Late onset Juvenile pompe presents later than infancy and typically does not include severe cardiomyopathy Adult onset is characterised by a slowly progressive myopathy (muscle weakness) that presents as an adult The severity of the disease and the rate of disease progression varies from person to person. Listed below are the possible symptoms: Page 3
Cardiomegaly (enlarged heart) Lysosomal Cardiomyopathy Disorders (weak heart) rarely seen Profound/rapidly progressive - hypotonia (floppy baby) Delayed motor milestones Frequent infections Respiratory insufficiency Cardio-respiratory failure (death) Failure to thrive, feeding difficulties Organomegaly enlarged liver, spleen & tongue Progressive proximal muscle weakness (esp. trunk and lower limbs) Gait abnormalities Muscle pain Difficulty climbing stairs Frequent falls Scapular winging Respiratory failure/insufficiency Morning headache & day time tiredness Orthopnea ( breathing difficulties when laying down) Sleep apnea ( stopping breathing whilst asleep) Exertional shortness of breath Respiratory infections Jaw muscle fatigue & swallowing difficulties At risk of food aspiration Weight stability Osteoporosis/osteopenia Neurological & hearing impairment Osteoporosis/osteopenia Adult onset Infantile onset Treatment Enzyme replacement therapy (ERT) Until recently in the UK treatment for disease was limited to supportive therapy. In April 2006 Genzyme corporation received a product licence for Myozyme. This is the direct replacement of the missing enzyme in disease a treatment known as enzyme Page 4
replacement therapy (ERT) This is an intravenous infusion that is give once per fortnight initially in hospital but with the possibility of home infusion if hospital infusions are uneventful. The infusion takes between 4-5 hours to give. This treatment is considered to be an orphan drug" and as such prescribing in England is restricted to NCG centres. In Scotland, Wales and N Ireland, permission must be obtained from the devolved NHS authorities in each region. Side effects are generally mild but may include: Hypersensitivity anaphylactic shock has been reported in a few patients Infusion reactions agitation, tremor, tachycardia (fast heart rate), cyanosis, flushing, hypertension (high blood pressure), pallor, tachypnoea (fast breathing), cough, vomiting, urticaria (rash), fever, rigors (chills), decreased oxygen saturation, hypotension (low blood pressure) & tachycardia (fast heart rate) Note: reactions are more likely if a patient has an acute underlying illness at the time of the Page 5
infusion, or if they have reacted to myozyme before. Supportive treatment This will vary considerably depending upon the nature and severity of the symptoms experienced. is a progressive disorder and therefore requires regular assessment to identify which treatments are appropriate. In general these tests should include assessment of cardiac and respiratory function (heart and lung), muscle strength and function, safety when swallowing and diet/weight maintenance. It is likely that people affected by pompe will also need to visit other doctors eg a neurologist, respiratory and/or cardiac physician as well as other healthcare professionals such as the physiotherapist, occupational therapist, speech therapist and dietician. At Addenbrooke s, patients are cared for by an experienced metabolic physician and a specialist nurse who will co-ordinate assessment, treatment and supportive care as necessary, with access to the multi disciplinary team. The input and support of a local physician is also essential. It is considered important for patients to adopt a healthy lifestyle by following dietary advice, exercising within limits and to avoid smoking in order to maintain or improve general health. Page 6