G6PD Deficiency in Babies and Families: Screening, Test Results and Inheritance

This page focuses on G6PD deficiency in babies, screening, test results and inheritance. For the full disease overview, see glucose-6-phosphate dehydrogenase deficiency. For a practical list of foods, medicines and household products to avoid, see G6PD deficiency: foods and medicines to avoid.

Why the G6PD enzyme matters: the pentose phosphate pathway

Red blood cells have no nucleus and cannot make new proteins, so they rely on a small set of enzymes to survive about 120 days. G6PD is the first step in the pentose phosphate pathway, the only source of NADPH in a red cell. NADPH keeps glutathione in its active form, and glutathione neutralizes oxidants such as hydrogen peroxide.

When G6PD is low, oxidative stress from infections, certain drugs or fava beans overwhelms the cell. Hemoglobin clumps into Heinz bodies, the spleen removes damaged cells, and the cells burst inside blood vessels. This sudden destruction (acute hemolysis) causes the symptoms: pallor, fatigue, a fast heartbeat, jaundice and dark urine from released hemoglobin. Between episodes, most people have no symptoms at all.

G6PD deficiency in newborns

Babies with G6PD deficiency are about twice as likely to develop significant newborn jaundice. The cause is partly faster red cell breakdown and partly a slower liver processing of bilirubin, especially when the baby also carries a common variant of the UGT1A1 gene (Gilbert-type).

Warning patterns in a baby with G6PD deficiency:

• Jaundice appearing in the first 24 hours
• Bilirubin rising faster than expected, sometimes suddenly after discharge
• A trigger such as naphthalene mothballs on clothes or bedding, or certain herbal remedies taken by a breastfeeding mother

Very high bilirubin can damage the brain, a condition called kernicterus, which causes hearing loss, cerebral palsy and developmental problems. It is preventable with timely phototherapy. The American Academy of Pediatrics now lists G6PD deficiency as a risk factor that lowers the bilirubin threshold for treatment, and recommends checking G6PD activity in babies with jaundice needing phototherapy when the cause is unclear or the family background suggests risk.

Treatment of newborn jaundice with G6PD deficiency

• Phototherapy: blue light breaks down bilirubin in the skin.
• Exchange transfusion: replaces the baby's blood when bilirubin is dangerously high or rising despite phototherapy.
• Feeding support: frequent feeds help clear bilirubin through stool.
• Removing triggers: keep mothballs, henna and camphor away from the baby.

Newborn screening for G6PD deficiency

Screening practice varies:

• Many countries with high rates, including parts of Asia, the Middle East and the Mediterranean, screen all newborns.
• In the US, G6PD is not on the core federal screening panel, but some states and hospitals test, and many test jaundiced babies or those at higher risk.

If your baby was not screened and you have a family history or a background from a high-prevalence region, ask the pediatrician about testing.

Understanding G6PD test results

Typical interpretation

• Normal: activity above about 80% of the normal median.
• Intermediate: about 30 to 80%. Common in heterozygous females. Some drugs, such as tafenoquine for malaria, require normal activity.
• Deficient: below about 30%. The person is at risk of hemolysis with triggers.

These cutoffs are approximate and each laboratory reports its own reference range.

Why a result can be falsely normal

During or just after a hemolytic episode, the oldest and most deficient red cells have been destroyed. The young cells that remain have more enzyme, so the test can look normal. A recent blood transfusion has the same effect. If a result is normal but hemolysis was clearly triggered, repeat the test about 3 months later.

How G6PD deficiency is inherited

The G6PD gene sits on the X chromosome.

• Males have one X. If it carries the variant, they are affected (hemizygous).
• Females have two X chromosomes. With one changed copy, they are heterozygous carriers. Because one X is randomly switched off in each cell, carriers can have anything from normal to clearly low activity, and some have hemolysis.
• Females with two changed copies (homozygous) are affected like males.

Fathers never pass G6PD deficiency to their sons, because sons receive the father's Y chromosome.

Variants and severity

The WHO groups variants by enzyme activity and symptoms. The common African variant (A-) usually causes milder, self-limiting episodes. The Mediterranean variant causes more severe hemolysis and is the one most linked to favism. A rare group of variants causes ongoing hemolytic anemia even without triggers.

Caring for a child with G6PD deficiency

• Tell every doctor, dentist and pharmacist. Keep a written diagnosis and a list of unsafe medicines.
• Avoid fava beans, naphthalene mothballs and henna.
• Check before giving any new medicine, including over-the-counter and herbal remedies.
• Treat infections promptly, since infection is the most common trigger of hemolysis in children.
• Know the signs of hemolysis: pallor, tiredness, yellow eyes and dark urine.

Frequently asked questions

Is G6PD deficiency in babies serious?

Most babies with G6PD deficiency do well. The main risk is severe newborn jaundice, which can damage the brain if bilirubin gets very high. With monitoring and phototherapy when needed, this is preventable. After the newborn period, most children only have problems if they meet a trigger.

Can a girl have G6PD deficiency?

Yes. Girls who inherit one changed gene are carriers and can have low enzyme activity in some red cells, enough to cause hemolysis with strong triggers. Girls with two changed genes are fully affected. Standard screening tests can miss carriers, so a quantitative test is better for females.

What does a G6PD test result of "deficient" mean?

It means your red blood cells have too little G6PD enzyme activity to handle oxidative stress, usually below about 30% of normal. You are not anemic all the time, but certain medicines, fava beans, mothballs and infections can trigger red cell breakdown. Ask for a list of drugs to avoid.

Can G6PD deficiency skip a generation?

It can seem to. A grandfather with G6PD deficiency passes the gene to all his daughters, who are usually healthy carriers. Each of their sons then has a 50% chance of being affected. That pattern can make the condition look as though it skipped a generation.

What are the symptoms of G6PD deficiency in the pentose phosphate pathway?

G6PD is the first enzyme of the pentose phosphate pathway, which makes NADPH to protect red cells. When it is low, oxidative stress causes red cells to break down. Symptoms appear only during these episodes: pallor, tiredness, fast heartbeat, jaundice, dark urine and sometimes back or belly pain.

Does G6PD deficiency go away?

No. It is lifelong because it is genetic, but most people never have symptoms if they avoid triggers. Babies who needed phototherapy for jaundice usually grow up healthy. Enzyme levels do not improve with age, so the trigger precautions apply for life.