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Health condition

Inherited metabolic disorders, newborn screening, specialist centres and modern therapies.

Individually rare, together common. A UK-focused hub covering PKU, urea cycle disorders, lysosomal storage disease, mitochondrial disease and more.

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Why trust this guide

  • 01

    Editorial team

    Written by our editorial team from the UK sources listed on each page.

  • 02

    Sourced from guidance

    Checked against BIMDG, MetBioNet, NICE and the UK Newborn Blood Spot Screening Programme.

  • 03

    Current for 2026

    Reflects the current UK expanded newborn screening panel, NHS specialist commissioning and modern therapies including enzyme replacement and gene therapy.

Key facts

Metabolic disease at a glance.

The essentials, in plain English - what these disorders are, how the UK finds them and how they are treated today.

  • What it is

    A large family of inherited (usually autosomal recessive) disorders where a single enzyme or transporter fault blocks a metabolic pathway.

  • Also called

    Inborn errors of metabolism (IEM). Individually rare, collectively affect roughly 1 in 800 UK births.

  • Newborn screening

    The UK blood spot picks up nine conditions including PKU, MCAD, MSUD, IVA, GA1, HCU, sickle cell, cystic fibrosis and congenital hypothyroidism.

  • Major groups

    Amino acid, urea cycle, organic acid, fatty acid oxidation, lysosomal storage, mitochondrial, glycogen storage, peroxisomal and metal disorders.

  • Care setting

    Specialist commissioned NHS metabolic centres (Great Ormond Street, Birmingham, Alder Hey, Manchester/Salford) lead diagnosis and long-term care.

  • Modern therapies

    Diet, cofactors, enzyme replacement, substrate reduction, chaperones, transplant and, for a growing number, gene therapy.

Why this guide matters

The twelve groups you actually meet in clinic.

Metabolic medicine is broad but pattern-driven. These twelve groups cover the vast majority of what a specialist commissioned UK centre will see.

  • 1. Amino acid disorders

    PKU (phenylketonuria), maple syrup urine disease, tyrosinaemia, homocystinuria and ornithine transcarbamylase deficiency.

  • 2. Urea cycle disorders

    OTC deficiency, argininosuccinic aciduria and citrullinaemia - hyperammonaemia is the shared emergency.

  • 3. Organic acidaemias

    Methylmalonic, propionic, isovaleric and glutaric acidaemia - decompensation with acidosis during illness.

  • 4. Fatty acid oxidation

    MCAD, VLCAD and LCHAD - hypoketotic hypoglycaemia and Reye-like episodes.

  • 5. Lysosomal storage disorders

    Gaucher, Fabry, Pompe, MPS I to VII, Niemann-Pick and Krabbe - many now treatable with enzyme replacement or gene therapy.

  • 6. Mitochondrial disease

    MELAS, MERRF, Leigh syndrome and LHON - multi-system disease with the UK now offering mitochondrial replacement therapy for selected families.

  • 7. Glycogen storage diseases

    GSD types I to XV - hypoglycaemia, hepatomegaly and, in later types, muscle disease.

  • 8. Peroxisomal disorders

    X-linked adrenoleukodystrophy and Zellweger spectrum - very-long-chain fatty acids are the key test.

  • 9. Metal disorders

    Wilson disease (copper) and haemochromatosis (iron) - two treatable adult-onset conditions.

  • 10. Porphyrias

    Acute intermittent porphyria and erythropoietic protoporphyria - abdominal pain, neuropathy and skin sensitivity.

  • 11. Carbohydrate disorders

    Galactosaemia and hereditary fructose intolerance - dietary avoidance is transformative.

  • 12. Other and vascular

    Hereditary haemorrhagic telangiectasia (HHT) and rarer connective, endocrine and vascular genetic disorders.

How the diagnosis is made

From first suspicion to a specialist plan.

The steps a UK metabolic team will normally follow, in order - so you know what to expect and why.

  1. 01

    Assessing

    Family and pregnancy history

    Consanguinity, unexplained infant deaths, developmental regression or a known family diagnosis - all raise the index of suspicion.

  2. 02

    Assessing

    Presenting picture

    Neonatal collapse, failure to thrive, developmental delay, seizures, hepatosplenomegaly, hypoglycaemia or unexplained acidosis and coma.

  3. 03

    Assessing

    Newborn blood spot

    Day 5 heel-prick screens for PKU, MCAD, MSUD, IVA, GA1 and HCU alongside three non-metabolic conditions - a national safety net.

  4. 04

    Confirming

    First-line biochemistry

    Ammonia, lactate, glucose, ketones, blood gas, liver and creatine kinase - the pattern often points to the group.

  5. 05

    Confirming

    Specialist metabolic panel

    Plasma amino acids, urine organic acids, acylcarnitine profile, very-long-chain fatty acids and urine mucopolysaccharides where indicated.

  6. 06

    Confirming

    Enzymology and imaging

    White cell or fibroblast enzyme assays, MRI brain, echocardiography and ophthalmology - guided by the suspected group.

  7. 07

    Genetics

    Genetic confirmation and MDT

    Targeted panels, whole-exome or whole-genome sequencing confirm the diagnosis and open the door to a specialist commissioned MDT plan.

Typical pathway: a first suspicion to a specialist MDT plan in days, not months.

Symptoms

What metabolic disease actually looks like.

The classic patterns that should trigger a specialist metabolic referral - and the features that mean a child or adult needs urgent assessment now.

  • Neonatal collapse

    A previously well baby who deteriorates in the first days of life - drowsiness, poor feeding, tachypnoea and encephalopathy point to a metabolic emergency.

  • Failure to thrive

    Poor weight gain, vomiting and feeding aversion, often with subtle biochemical clues on routine bloods.

  • Developmental delay or regression

    Missed milestones or the loss of previously acquired skills - a red flag for lysosomal, mitochondrial and peroxisomal disorders.

  • Seizures and encephalopathy

    Difficult-to-treat neonatal seizures, movement disorders and unexplained coma need urgent metabolic assessment.

  • Hepatosplenomegaly

    A big liver and spleen with abnormal bone, eye or skin findings suggest a lysosomal storage disorder.

  • Hypoglycaemia and acidosis

    Recurrent low blood sugar, high anion-gap acidosis or high ammonia during illness are classic decompensation triggers.

  • Adult-onset presentations

    Fabry, Wilson, haemochromatosis, porphyria and mitochondrial disease often first show themselves in adulthood.

  • Red flag - metabolic emergency

    Any child with unexplained coma, high ammonia or severe acidosis needs immediate transfer to a specialist commissioned metabolic team.

Treatment

How metabolic disease is treated in the UK.

Diet and cofactors first, enzyme replacement, chaperones and substrate reduction where available, and transplant or gene therapy for the most severe forms.

  • Specialist metabolic diet

    Phenylalanine restriction in PKU, protein restriction in MSUD, tyrosinaemia and urea cycle disorders - all guided by a specialist commissioned metabolic dietitian.

  • Cofactors and vitamins

    Sapropterin for responsive PKU, biotin, B12 and carnitine for selected organic acid and fatty acid oxidation disorders.

  • Enzyme replacement therapy

    Imiglucerase and velaglucerase for Gaucher, agalsidase for Fabry, alglucosidase for Pompe and elosulfase or galsulfase for MPS - specialist commissioned NHS infusion services.

  • Chaperone and substrate therapy

    Migalastat stabilises the Fabry enzyme in amenable variants. Miglustat and eliglustat reduce substrate load in Gaucher disease.

  • Bone marrow transplant

    Haematopoietic stem cell transplant transforms outcomes in early-treated Hurler (MPS I) and cerebral X-linked adrenoleukodystrophy.

  • Liver and organ transplant

    Liver transplant is the definitive option for severe urea cycle disorders and selected organic acidaemias - a specialist commissioned pathway.

  • Gene therapy

    Approved and trial gene therapies for X-linked ALD, MPS and other lysosomal disorders - delivered through a specialist commissioned clinic.

  • Emergency regimens

    Written emergency plans, glucose polymer drinks and rapid hospital access during illness protect against metabolic decompensation.

What this guide is based on

The sources behind every claim on this page.

UK national guidance, NHS service specifications and specialist society standards, current at the time of last review.

Key references

Guidelines and standards we relied on.

A quiet reminder

This guide is for information, not medical advice.

Your NHS metabolic team knows the diagnosis, the emergency plan and the current therapies for your family. If in doubt, get in touch with them or your GP.

  • British Inherited Metabolic Disease Group (BIMDG). Emergency and management guidelines.

  • NHS England. Specialised services service specifications for inherited metabolic disorders (adult and paediatric).

  • UK Newborn Blood Spot Screening Programme. Handbook and expanded panel guidance.

  • NICE and BNF. Guidance on enzyme replacement therapies, sapropterin, migalastat and related medicines.

  • Metabolic Support UK and MetBioNet. Patient information and laboratory best-practice standards.

Red flags

When metabolic disease needs urgent attention.

Most people with an inherited metabolic disorder are safe with a plan. These are the moments when that plan needs to be activated straight away.

  • Neonatal metabolic emergency

    Hyperammonaemia, severe acidosis or unexplained coma in a newborn - stop feeds, give glucose and transfer to a specialist commissioned metabolic centre.

  • Missed newborn screening

    A baby born outside the UK or with an incomplete blood spot - arrange screening or targeted testing without delay.

  • Developmental regression

    Loss of previously acquired milestones is never simply a plateau - it warrants urgent metabolic and neurology review.

  • Cardiomyopathy in a child

    Unexplained hypertrophic or dilated cardiomyopathy can be the first sign of Pompe, fatty acid oxidation or mitochondrial disease.

  • Recurrent Reye-like episodes

    Vomiting, hypoglycaemia and encephalopathy with viral illness - think MCAD and other fatty acid oxidation defects.

  • Adult stroke without vascular risk

    A young adult stroke, especially with hearing loss or diabetes, can be MELAS or Fabry disease.

  • Unexplained hepatosplenomegaly

    Consider Gaucher, Niemann-Pick and glycogen storage disease before labelling as idiopathic.

  • Family history of infant deaths

    Two or more unexplained neonatal or infant deaths in a family need genetic and metabolic assessment before the next pregnancy.

  • Acute porphyric attack

    Severe abdominal pain, neuropathy and dark urine after certain drugs - treat as a porphyria emergency until proven otherwise.

Living with it

A lifelong condition, with a clear team behind you.

Four things that make the biggest difference day to day - a written emergency plan, a specialist commissioned metabolic team, family testing and community support.

A quiet reminder

Small, steady habits protect the biggest gains.

Diet, medications and annual reviews only work when they are part of an ordinary routine, not an emergency response.

  1. 01 Plan

    Keep the emergency plan close

    A written BIMDG-style plan, glucose polymer drinks and a direct hospital contact turn frightening illnesses into manageable ones.

  2. 02 Team

    Stay linked to the specialist centre

    Annual review with a specialist commissioned metabolic MDT keeps therapy, growth and complications on track through childhood and adult life.

  3. 03 Family

    Cascade and prenatal options

    Genetic counselling, cascade testing for siblings and prenatal or preimplantation options are all part of routine care.

  4. 04 Community

    Use the patient community

    Metabolic Support UK, MPS Society, Gauchers Association and disease-specific charities offer practical help and peer expertise.

Frequently asked

Everything we get asked about inherited metabolic disorders.

Quick answers on screening, diagnosis, NHS treatment and family planning.

  • What are inherited metabolic disorders?

    They are a large family of inherited (usually autosomal recessive) conditions where a single enzyme or transporter fault blocks a metabolic pathway. Individually rare, they collectively affect around 1 in 800 UK births and range from silent adult-onset conditions to life-threatening neonatal emergencies.

  • How are they diagnosed in the UK?

    The day 5 newborn blood spot screens for PKU, MCAD, MSUD, IVA, GA1 and homocystinuria. Beyond screening, diagnosis rests on plasma amino acids, urine organic acids, acylcarnitine profiles, enzymology and genetic testing coordinated through a specialist commissioned NHS metabolic centre such as Great Ormond Street, Birmingham, Alder Hey or Manchester and Salford.

  • Which conditions does the newborn blood spot cover?

    Nine in total - phenylketonuria, medium-chain acyl-CoA dehydrogenase deficiency (MCAD), maple syrup urine disease, isovaleric acidaemia, glutaric aciduria type 1 and homocystinuria, alongside sickle cell disease, cystic fibrosis and congenital hypothyroidism. Anything else needs targeted testing when there are clinical clues.

  • What treatments are actually available on the NHS?

    Diet and cofactors for many amino acid and organic acid disorders, enzyme replacement therapy for Gaucher, Fabry, Pompe and several MPS conditions, chaperone therapy with migalastat for amenable Fabry variants, bone marrow transplant for Hurler and cerebral X-linked ALD, liver transplant for severe urea cycle disorders, and an expanding list of gene therapies delivered through specialist commissioned clinics.

  • When should I suspect a metabolic disorder in an unwell child?

    Unexplained neonatal collapse, high ammonia, severe acidosis, recurrent hypoglycaemia, unexplained encephalopathy, developmental regression, hepatosplenomegaly, cardiomyopathy or a family history of unexplained infant deaths should all prompt urgent metabolic assessment.

  • What about family planning?

    Most inherited metabolic disorders are autosomal recessive, so siblings and future children can be affected. A clinical genetics team can offer cascade testing, carrier testing for partners, prenatal diagnosis and preimplantation genetic testing through NHS specialist commissioning.

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