Metabolic Medicine clinical outcomes

Clinical outcomes are measurable changes in health, function or quality of life that result from our care. Constant review of our clinical outcomes establishes standards against which to continuously improve all aspects of our practice.

About the Metabolic Medicine Service

Great Ormond Street Hospital’s (GOSH) service is the largest paediatric metabolic centre in the UK. We are the principal provider of specialist child metabolic medicine services for London (north of the Thames) and the surrounding counties, and we provide a national and international service for the management of rare and complex paediatric metabolic conditions.

We see patients from 0 to 16 years old with suspected or diagnosed metabolic disease, including disorders of intermediary metabolism, neurometabolic disorders, congenital disorders of glycosylation (CDG), disorders detected on newborn screening, galactosaemia, familial hypercholesterolaemia (FH) and mitochondrial disorders. We are one of three nationally-commissioned NHS specialised services for the management of children with lysosomal storage disorders (LSD).

The Clinical Biochemistry department at GOSH is one of the UK newborn screening centres. The Metabolic Medicine Service provides care for all neonates from our catchment area with positive neonatal screening results, which include phenylketonuria (PKU), medium-chain acyl-CoA dehydrogenase deficiency (MCADD), glutaric aciduria type 1 (GA1), isovaleric acidaemia (IVA), maple syrup urine disease (MSUD) and homocystinuria (HCU).

Our multi-disciplinary metabolic team is comprised of consultants and clinical nurse specialists, with specialist input from metabolic dieticians, biomedical scientists, physiotherapists, clinical psychologists, social workers, and speech and language therapists.

Clinical outcome measures

1. Home treatment for Lysosomal Storage Disorder (LSD)

LSD is an umbrella term for a group of more than 50 genetic disorders that are caused by a lysosomal enzyme deficiency. Worldwide, these conditions affect an estimated one in 7,700 people.

Many of the LSDs display a progressive disease pattern, which means that symptoms get worse over time if left untreated. Treatments for some of the LSDs include enzyme replacement therapy (ERT), which is administered intravenously every week or two, depending on the type of disorder. 

It is important for the wellbeing of the child and their family to seek, where possible, to reduce disruption caused by the treatment frequency. Home infusion can help, with fewer days of school missed, less disruption for parents and siblings, and reduced travel and financial implications. 

Home infusion can only be an option if it can be established safely with patient/family training, with protocols in case of infusion reactions, and with support from the specialist centre. 

1.1 Children with an LSD on home ERT

Table 1.1 Number of children with an LSD on home ERT

Number of patients with an LSD on home ERT

Patients as at March 2018

Number of current patients with an LSD


Number of current patients with an LSD on home ERT


Percentage of current patients with an LSD on home ERT


Of 104 current GOSH patients (as at March 2018), for whom homecare is suitable, all 104 (100 per cent) are on home ERT.

1.2 Children with an LSD on ERT who are transferred to home infusions within three months of commencement of therapy

Table 1.2 Number of children with an LSD on ERT who are transferred within three months of commencement of therapy, 2015-16 to 2017-18

New patients with an LSD on ERT who are transferred to home infusions


2016/17 2017/18
Patients transferred within three months 8 4 5
Patients transferred after three months 4 4 0
Total number of patients 12 8 5
Percentage of patients transferred within three months 67% 50% 100%

For 2017/18, 5 (100%) of children were transferred to home ERT within three months of commencement of therapy.

For April 2015 to March 2018, 17 (68%) children were transferred to home ERT within three months of commencement of therapy. Eight (32%) of children were transferred after three months because they had severe infusion reactions and were kept longer in order to get them on pre-infusion medication that stopped the reactions.

2. Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) seen for review

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a rare inherited genetic disorder in which there is a block in the metabolism of fat into energy when the body's demand for energy increases and calorie intake is often reduced. This means that when someone with MCADD develops an illness, such as diarrhoea and vomiting or an infection that prevents them eating, they are at risk of becoming more unwell, and they are also at risk of developing hypoglycaemia. 

MCADD is a lifelong condition that is present from birth. It is estimated to affect up to 1 in every 8,000 babies born in the UK and is usually picked up using the newborn blood spot test. Medical complications of the condition can usually be prevented, so early detection and medical management is very important.

2.1 Patients with MCADD seen for review within 24 hours

Newly identified patients with MCADD should be seen for a 'face-to-face review' within 24 hours of receiving information about the newborn screening result. At the review, they are provided with necessary information and an emergency regimen, which is a special feeding plan to provide patients with energy if they are unwell or unable to take their normal nutritional intake.

Numerator: The number of newly identified MCADD Newborn Screening (NBS) patients seen for a 'face-to-face review ' by the metabolic clinical team within 24 hours of receiving the screening report and provided with necessary information and emergency regimen.

Denominator: Total number of new positive diagnoses of MCADD by NBS at the centre.

Table 2.1 Number of MCADD patients seen for a review within 24 hours

MCADD patients seen for review


2016/17 2017/18

Number of newly identified MCADD NBS patients seen for a 'face-to-face' review by metabolic clinical team within 24 hours

8 8 5
Total number of new positive NBS diagnoses of MCADD 8 8 9
Percentage of newly identified MCADD NBS patients seen for a 'face-to-face' review by metabolic clinical team within 24 hours 100% 100% 56%

This measure is a national measure that is reported to commissioners by MCADD specialised services. In 2017/18, all patients received clinically appropriate care and were provided with the necessary information and an emergency regimen. As per national protocol, we see patients on the next working day after diagnosis. Therefore, a small number of patients who were diagnosed on the weekend were seen on the next working day, rather than ‘within 24 hours’. One patient was admitted to another hospital and was seen at GOSH once clinically stable. For clinically appropriate reasons one patient was not seen ‘face-to-face’, though the treatment and information were provided at birth, before newborn screening. This patient was subsequently seen at GOSH for a review.

3. Review of emergency regimen for children with organic acidaemia conditions

Children and young people with metabolic conditions will often need to follow an emergency regimen diet when they become ill (such as vomiting or diarrhoea) to help prevent deterioration of metabolic function and a possible admission to hospital. This involves drinking a special high glucose drink at specific times until they are able to resume their regular diet. This is particularly important for those with a group of conditions called organic acidaemias.

3.1 Patients with PA or MMA (non-vitamin B12 responsive) provided with an emergency regimen

A measure of our effectiveness that we report to NHS England each year is the number of patients with propionic acidaemia (PA) or methylmalonic acidaemia (MMA) that is non-Vitamin B12 responsive, who have an emergency regimen as per the British Inherited Metabolic Disease Group guidelines (

Fig 3.1: Percentage of patients with PA or MMA (non-vitamin B12 responsive) provided with an emergency regimen

Percentage of patients with PA or MMA provided with an ermergency regimen

These results show that 100% of our children and young people with these conditions are provided with an emergency regimen. This means that parents/carers are able to promptly implement the appropriate emergency regimen at home at the start of any illness that disrupts their child’s regular diet. This helps to avoid the co-occurrence of potentially serious metabolic problems when their child is unwell. 

3.2 Patients with PA or MMA (non-vitamin B12 responsive) with an appropriate emergency regimen, reviewed at least yearly

To ensure that the emergency regimen is up-to-date for each patient, the regimen should also be reviewed at least yearly and adjusted accordingly.

This measure shows the number of children and young people with PA or MMA (non-vitamin B12 responsive) whose emergency regimen has been reviewed within 12 months. To ensure relevance of the data, patients who moved countries, transitioned to adult health services or died prior to their review date are not included in the figures.

Fig 3.2 Percentage of patients with PA or MMA (non-vitamin B12 responsive) with an appropriate emergency regimen, reviewed at least yearly

Percentage of patients with PA or MMA with an appropriate emergency regimen reviewed at least yearly

Our results show that we have a near 100% achievement of yearly review of emergency regimens for our children and young people with PA or MMA (non-vitamin B12 responsive). This means that if they do become unwell, they can be given an up-to-date emergency regimen diet that is most appropriate for their age and weight to support their metabolic function during sickness.

4. Patients with Familial Hypercholesterolaemia who have been DNA tested

Familial hypercholesterolaemia (FH) is an inherited condition characterised by high levels of LDL-cholesterol. It results from mutations in genes affecting cholesterol metabolism. High cholesterol levels lead to atherosclerotic plaque deposition in the blood vessels causing premature coronary heart disease. With the right treatment the onset and severity of symptoms can be delayed. Diagnosis is based on the use of diagnostic criteria and there are currently three formal diagnostic criteria for FH widely used in Western countries. The identification of a pathogenic variant in a gene known to be associated with FH is nevertheless the gold standard for diagnosis. Published guidelines from the National Institute for Health and Care Excellence includes the standard, ‘Healthcare professionals should offer people with a clinical diagnosis of FH a DNA test to increase the certainty of their diagnosis and to aid diagnosis among their relatives.’

Here at GOSH, we follow this standard and we measure our performance against it to ensure that we perform DNA testing as part of the care we provide to our patients and their families. To standardise our approach to clinical diagnosis for this measure, we use the Simon Broome criteria as our first screen method for establishing a clinical diagnosis of FH.

The greater the number of patients with possible FH whose diagnosis is confirmed through DNA testing:

  • the more we can work with pro-actively to postpone any effects of the condition upon the cardiovascular system
  • the greater the number of families we can work with to aid diagnosis among family members

Table 4.1 Patients with possible FH who are DNA tested

Patients meeting Broome criteria

DNA tested

FH confirmed by DNA test

FH not confirmed by DNA test

DNA not tested













The table above shows that for 2016/17, 37 patients met the Simon Broome criteria for a clinical diagnosis of FH. Of these, 34 (92%) were DNA tested. Out of the patients who had DNA testing, 32 (94%) were genetically confirmed to have FH. This is in accordance with results from literature stating that genetic confirmation is accomplished in 70-95% of patients by testing for mutations in the most common genes affecting cholesterol metabolism.

We have additionally performed DNA testing on 14 out of 18 patients with high cholesterol levels but who did not meet the Simon Broome criteria. Six patients from that group were genetically confirmed as well, showing that criteria are helpful, but must be used in conjunction with clinical judgement to avoid missing FH confirmations. Genetic results have been communicated to the family and local doctors/GPs in order to proceed to further family member screening.

This information was published in October 2018 and will be updated in October 2019.