Table 1

Inherited metabolic disorders associated with epilepsy that are currently screened for in the UK

DisorderTypical clinical features that may be present in adult patientsGene (s)Main biochemical abnormality (initial investigative test in adulthood)Year in which universal UK newborn screening started (UK incidence, live births)*
PKULearning difficulties, eczema, parkinsonismPAH Increased phenylalanine (plasma amino acid profile)1970 (1 in 10 000)
MCADDLearning difficultiesACADM Increased C8:C10 ratio (acylcarnitine profile)2013 (1 in 10 000)
MSUDLearning difficulties, spastic diplegiaBCKDHA, BCKDHB, DBT Increased leucine, isoleucine, valine. Detectable alloisoleucine (plasma amino acid profile)2015 (1 in 200 000)
IVALearning difficultiesIVD Increased C5 carnitine (acylcarnitine profile). Increased isovalerylglycine (urine organic acid profile).2015 (1 in 100 000)
GA1Movement disorder with prominent dystoniaGCDH Increased 3-OH-GA (urine organic acid profile)2015 (1 in 100 000)
Homocystinuria (pyridoxine unresponsive)†Learning difficulties, thrombotic events, lens dislocation, marfanoid featuresCBS Increased homocysteine (plasma amino acid profile)2015 (1 in 100 000)
  • *Reference: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/642333/IMD_laboratory_handbook_2017.pdf

  • †People with homocystinuria (HCU) that present first in adulthood are often pyridoxine responsive. Individuals who are pyridoxine responsive are less likely to have other clinical clues such as marfanoid features, lens dislocation or learning difficulties. A typical clinical presentation to a neurologist of pyridoxine responsive HCU might be with a cerebral thrombosis and seizures. Pyridoxine responsive individuals are not picked up by current newborn screening methods and will therefore continue to present clinically.

  • GA1, glutaric aciduria type 1; IVA, isovaleric acidaemia; MCADD, medium-chain acyl-CoA dehydrogenase deficiency; MUSD, maple syrup urine disease; PKU, phenylketonuria.