Glutaric aciduria type 1 (GA1)

GA1 is an inherited organic acid disorder. An enzyme called glutaryl-CoA dehydrogenase is missing, so the body cannot process the amino acids lysine and tryptophan, which are building blocks of protein. Glutaric acid and a related substance, 3-hydroxyglutaric acid, accumulate in the brain and body.

The basal ganglia, the part of the brain that controls movement, are particularly vulnerable. Untreated, GA1 can cause long-term brain damage and physical disability, but with newborn screening and early treatment this can be prevented. Medical genetics summaries note that some babies are born with an unusually large head.

Babies with GA1 are usually healthy at birth. The risk is a metabolic crisis, also called metabolic decompensation, which is a rapid build-up of the harmful substances. It is usually triggered by childhood infections that cause fever, vomiting or diarrhoea, because illness makes the body break down its own protein.

A crisis can cause irritability, sleepiness and non-responsiveness, floppiness and falling over, poor feeding, breathing difficulties, seizures and coma. It can lead to serious illness and long-term brain damage and can be life-threatening. The sudden injury can produce lasting dystonia and other movement problems, with only partial recovery, which is why prevention matters more than treatment after the event.

• Early signs of trouble in a baby or toddler: not feeding well, unusual sleepiness, floppiness or new jerky movements.

• Fever that does not respond to normal fever medicine needs prompt treatment, as the NHS family leaflet stresses.

The newborn blood spot test, taken when a baby is about 5 days old, measures a substance called acylcarnitine, C5-DC. A high level suggests GA1 and is a screen positive result. The family is seen by a metabolic doctor, dietitian and specialist nurse, and blood and urine tests confirm or exclude the diagnosis.

While waiting for results parents can continue to breastfeed or give normal infant formula, feeding every 3 to 4 hours day and night or more often on demand. If the baby becomes unwell in this window they should be taken to hospital for assessment. Screening is a first step and does not replace clinical judgement: a child who develops unexplained movement problems or sudden drowsiness during illness still needs urgent metabolic assessment.

Treatment has three parts. The diet limits lysine and tryptophan while giving enough protein for growth. Babies receive a limited daily volume of breast milk or ordinary infant formula alongside a lysine-free, tryptophan-low infant formula, and the metabolic dietitian sets amounts by weight. The GP is asked to prescribe the special formula and the glucose polymer used in emergencies.

L-carnitine is a medicine that helps reduce glutaric acid in the blood. Regular blood tests check amino acid and nutrient levels and diet and medicines are adjusted with age, weight and results. With good management, severe movement problems can be prevented in the majority of children.

Family teaching covers a written emergency plan, keeping supplies in date and having them to hand, and keeping fever medicines available.

During illness an emergency regimen replaces normal protein feeds. It is made up of the GA1 specialist formula and glucose polymer powder, given regularly day and night to supply energy and limit the build-up of harmful substances. Metabolic Support UK summarises the steps: stop all protein in food and drink, start the regimen, continue carnitine as prescribed and phone the metabolic team.

Take the child to hospital immediately if they do not tolerate the emergency feeds, have an ongoing high temperature, or are getting worse. Bring the emergency regimen instructions, BIMDG guidelines, L-carnitine and the special formula. The British Inherited Metabolic Diseases Group publishes emergency guidelines for clinicians so that local hospitals can follow them; its adult guidance is suitable for patients over 40 kg.

GA1 is autosomal recessive. Both parents are carriers and in each pregnancy there is a 25% chance of an affected baby, a 50% chance of a carrier and a 25% chance of neither. Nothing the parents did could have prevented it.

In a later pregnancy the metabolic team writes a birth plan, which may include an extra blood spot test in the first days after birth in addition to routine screening. Parents should tell their midwife and GP about the family history and inform the metabolic team early. Metabolic Support UK reports roughly 1 in 100,000 children worldwide are thought to be affected.

Early diagnosis and treatment greatly improve outlook. Children identified by screening and managed well can avoid severe disability, whereas damage from a first crisis before diagnosis can be permanent. Care continues under the metabolic team throughout life, with adult metabolic services taking over in adolescence.