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Introduction to inherited metabolic diseases

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Many children with inherited metabolic diseases now survive to adulthood. These patients may present with complications in both primary and acute 


Citation: Lodwig J, Peers K (2013) Rare diseases 3: introduction to inherited metabolic disorders. Nursing Times; 109: 46, 28.

Authors: Jane Lodwig and Kate Peers are clinical nurse specialists in inherited metabolic disorders at University Hospitals, Birmingham.


Inherited metabolic diseases (IMDs) are a group of over 500 inherited conditions caused by deficient activity of a single enzyme (Burton and Sanderson, 2005).

These conditions are often life-limiting, multi-systemic and relentlessly progressive. The vast majority of IMDs present in childhood, but milder forms may present in adulthood, and there are also likely to be many undiagnosed adults.

Early diagnosis, the development of new treatments and improved management in childhood have resulted in increasing numbers of patients surviving to adulthood (Cochrane et al, 2007). This increase in survival age has meant people often develop chronic complications of their condition with increased morbidity (Thornes, 2001). Complications and co-morbidities are frequently managed in both primary and acute care as well as in tertiary referral centres.

IMD disorders

The majority of IMD are autosomal recessive, meaning that both parents carry one defective gene for a particular enzyme but are not affected. When each parent passes on their defective gene to an offspring, the offspring is unable to produce functioning enzymes that would normally be required for metabolism of protein, fat or carbohydrate. This leads to toxic accumulation of by-products that would normally be removed by that enzyme.

For example, in the amino acid disorder phenylketonuria (PKU), those affected are unable to metabolise the amino acid phenylalanine, and accumulation of phenylalanine in the brain causes profound learning difficulties. PKU is managed with a low protein prescription diet, which, if strictly adhered to, results in normal development. In the UK, screening for PKU takes place in infancy with a heel prick test. Early diagnosis and treatment has significantly improved outcomes for the majority of affected individuals.

Urea cycle disorders result in high blood ammonia levels (by-products of protein metabolism), which cause encephalopathy, coma and death if untreated. Patients are most at risk during times of inadequate calorie intake from fat or carbohydrate, such as during times of illness or starving before and after a general anaesthetic. At these times muscle protein becomes the major source of energy. These patients are managed with high carbohydrate emergency regimens as well as ammonia-scavenging medication. It is important to note that hyperammonaemia can mimic alcohol or drug-induced behaviours and patients can be misdiagnosed with tragic results.

Many patients with these conditions carry cards to alert health professionals.

Lysosomal storage disorders

The lysosome is often described as the “recycling centre” of the body. It uses enzymes to break down unwanted by-products of metabolism and ultimately remove them.

Patients with these conditions lack a lysosomal enzyme, which results in accumulation of these products in multiple organs. There are about 50 recognised LSDs, all with different symptoms depending on the defective enzyme. Patients can present at any age and it is worth considering LSD if you see a patient who appears to have several unrelated organs affected by disease.

Some LSDs are treated with enzyme replacement therapy. These expensive therapies are not a cure but may reduce symptoms and delay disease progression.

Box 1. Useful links

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Readers' comments (1)

  • My niece died in 1995, aged 8, with an autosomal recessive disease - Late Onset Battens Disease. Looking at it in a simplistic manner, it would seem that these diseases could be managed by supplementing the body with whatever is deficit. Having said that, I am not that naïve to realise it is not that simple. I just hope that there is a solution soon and that future families don't have to suffer.

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