What is an Inherited Metabolic Disorder?
‘Metabolism’ is the term given to all the life-sustaining chemical reactions that take place in the body. Inherited Metabolic Disorders (IMD) are a group of about 700-1000 rare disorders that affect the body’s metabolism.
Though collectively IMDs are not uncommon, the individual disorders are, thankfully, very rare. In the UK, at least 600 babies are born with an IMD every year. Currently there are around 20,000 children and adults living with an IMD in the UK, and half of those affected are not receiving treatment from a specialist service.
What causes an Inherited Metabolic Disorder?
A disorder occurs when there is a specific inherited, genetic defect in a vital chemical process in the body, which in turn leads to adverse effects on one or more organs. IMDs can occur either because of an excess of a toxic chemical caused by the metabolic defect, or due to a deficiency in a vital chemical caused by the defect.
What are the effects of an Inherited Metabolic Disorder?
The effects of an IMD vary in severity from mild and asymptomatic, to severe and life-threatening. Some IMDs worsen (decompensate) during stress, such as infection, starvation, and surgery. Although many IMDs are treatable, there are others, which do not yet have effective treatment.
There is a group of IMDs that affect development in babies and children. The difference between these IDMs compared with brain injuries suffered at birth, such as cerebral palsy, is that the damage to the brain - or to other organs - continues, meaning that not only do children fail to meet developmental milestones, but they may begin to regress and fall further behind.
Simon Towler of Shoosmiths’ clinical negligence team recently settled successfully two cases involving a failure to diagnose an IMD, leading to further injury. In both cases we argued that more tests should have been carried out to fully investigate the reasons for the developmental delay and regression.
Case one: ASA
In this disorder, there is a deficiency in the way the body breaks down a protein called Argininosuccinic Aciduria (ASA), which leads to an increase in the levels of ammonia in the body and, for reasons that are not understood, causes damage to the brain. About 1 in 70,000 babies are born with ASA; some become ill in the first few days of life, others may present later. The effects of high ammonia can quickly become life-threatening if untreated.
Signs and symptoms of ASA:
- Poor feeding
- Vomiting
- Floppiness
- Excessive sleepiness
- Rapid breathing
- Dehydration (lack of body fluids)
- Seizures
- Brittle hair
The child may have learning difficulties and delays in normal development, such as walking and talking, and it may also affect the liver or other parts of the body.
In ASA it is important that the patient is given enough protein to enable them to grow, but not too much, as waste protein causes high ammonia levels.
Our client was diagnosed with ASA after a delay of about four years. Once treatment was started the child showed real cognitive improvements, although the condition is incurable.
Case two: GAMT
Guanidinoacetate Methyltransferase (GAMT) Deficiency is an IMD that is characterised by neurological and muscular problems and is rarer than ASA. It is caused by defects in the GAMT gene which provides instructions to the body for making the guanidinoacetate methyltransferase enzyme, which is used to produce a compound called creatine, which the body needs to store and utilise energy. Only around 110 cases have been reported, and itis estimated that one-third of these are in people of Portuguese heritage.
Symptoms of GAMT deficiency often present from infancy up to three years of age and are more severe in organs and tissues that require large amounts of energy, such as the brain. The condition is characterised by mild to severe intellectual disability and a delay in reaching developmental milestones. Individuals may lose acquired skills such as sitting without support, and intellectual disability is linked with speech delay and behavioural problems. Without early treatment, neurological symptoms are often severe.
Symptoms of GAMT
- Speech delay or limited speech
- Involuntary movements
- Autistic spectrum disorders / ADHD.
- Epilepsy
Epilepsy is seen in most cases, and many different seizure types can result. The severity of seizures ranges from occasional to very serious seizures that do not respond to the usual anti-epileptic medication
Treatment includes high doses of oral creatine monohydrate along with ornithine supplements and/or dietary restriction of arginine. Dietary changes will be made following appointments with a specialist dietitian and regular follow-ups are required. Treatment improves some symptoms but it cannot reverse prior intellectual disability and developmental delay
In our client’s case, diagnosis was not made until they were 18 years old, a delay of over 16 years. Treatment has resulted in our client experiencing no further epileptic episodes and having more cognitive awareness and a much greater interest in life, amongst other improvements. Sadly, however it cannot change the damage caused in the years before to diagnosis.
IMDs are very rare, and a diagnosis cannot be made without a detailed set of tests and investigations, including extensive blood and genetic testing, MRI scans and MRS in some cases. For more information and support the charity Metabolic Support UK’s website provides details about metabolic conditions, medicines information, and access to peer support: Home - Metabolic Support UK.
Disclaimer
This information is for educational purposes only and does not constitute legal advice. It is recommended that specific professional advice is sought before acting on any of the information given. © Shoosmiths LLP 2025
