G6PD Deficiency

This G6PD deficiency article was contributed by Dr Yeoh Seen Hun, Consultant General Paediatrician at Pantai Hospital Cheras. To book an appointment or learn more about Dr Yeoh Seen Hun and his clinic, click here.

What is G6PD deficiency and what causes it?

G6PD deficiency (Glucose-6-phosphate dehydrogenase deficiency) is a genetic disorder caused by mutations in the G6PD gene. This enzyme plays a crucial role in protecting red blood cells from oxidative damage. A deficiency can lead to episodes of hemolysis (destruction of red blood cells) when triggered by certain foods, infections, or certain medications.

G6PD deficiency is relatively common in Malaysia, especially among male newborns due to its X-linked inheritance, meaning that the condition occurs when there is a mutation on the one X chromosome present in males.

Estimated prevalence: 3%-6% of Malaysian newborns, with higher rates reported in certain ethnic groups particularly among Malays and Chinese.

It is one of the conditions screened for in the Malaysian national newborn screening program, due to the potential for severe jaundice and hemolytic crises.

What are the signs and symptoms of G6PD deficiency in newborns and children?

Glucose-6-phosphate dehydrogenase (G6PD) deficiency can present with varying severity in newborns and children, often triggered by oxidative stress—an imbalance caused by reactive oxygen species, which the body cannot neutralise efficiently due to the impaired pentose phosphate pathway. Here's a concise breakdown of the clinical signs and symptoms by age group:

In Newborns:

1. Neonatal Jaundice

• Appears within the first 24-72 hours of life. Jaundice may be prolonged and severe, with total serum bilirubin rising rapidly.
• Risk of kernicterus (bilirubin-induced brain damage) if untreated. In the most serious cases, elevated bilirubin levels caused by rapid red blood cells break can require interventions like exchange transfusion to prevent permanent damage.

2. Dark Urine

• Caused by bilirubinuria or hemoglobinuria.

3. No obvious signs at birth

• Most are asymptomatic until exposed to a trigger.

In Older Infants and Children:

1. Acute Hemolytic Anemia (AHA)
   Triggered by:

• Certain foods (e.g., eating fava beans) Medications ( e.g., sulfa drugs, antimalarials, certain antibiotics)
• Infections

2. Signs/Symptoms of AHA:

• Sudden pallor, fatigue, or weakness
• Jaundice (new or worsening)
• Dark or tea-colored urine
• Rapid heart rate, shortness of breath
• Splenomegaly in some cases

In severe cases: hemoglobinuria, back or abdominal pain, possibly shock, mild anemia, intermittent jaundice, and gallstones.

Key Points

Many affected individuals are asymptomatic unless exposed to oxidative stress. Prompt recognition is crucial to prevent complications like severe anemia or neurological damage from hyperbilirubinemia. Routine screening is done in Malaysia to catch it early.

What foods, medications or substances should be avoided for children with G6PD deficiency?

For children with G6PD deficiency, exposure to certain oxidative agents can trigger hemolytic anemia, a potentially serious condition. The following foods, medications, and substances must be strictly avoided:

Foods to Avoid

1. Fava beans (broad beans) - the most well-known trigger (favism).
2. Tonic water (contains quinine).
3. Artificial food dyes - especially those with blue or synthetic derivatives (rare, but avoid if possible).
4. Naphthalene-containing items:
   • Mothballs
   • Some traditional herbal remedies

Medications (Drugs) to Avoid

These are oxidative drugs known to cause hemolysis:

• Antibiotics
  • Sulfonamides (e.g. cotrimoxazole, sulfamethoxazole)
  • Nitrofurantoin
  • Dapsone
  • Chloramphenicol

• Antimalarials
  • Primaquine
  • Quinine
  • Chloroquine (use with caution)

• Pain Relievers/ Antipyretics
  • Aspirin (especially high doses)
  • Phenazopyridine

• Others
  • Methylene blue
  • Rasburicase
  • High-dose vitamin C (uncommon, but large doses can be harmful)

Household or Environmental Substances

• Mothballs (naphthalene)
• Henna (black henna in particular) – may be absorbed through skin
• Strong oxidising disinfectants or cleaning agents - use in well-ventilated areas

Summary:

Children with G6PD deficiency should avoid oxidative stress, especially during illness or fever. Any prescription or over the counter medication should be double-checked by a pharmacist or physician familiar with G6PD contraindications.

How is G6PD deficiency tested and managed at Pantai Hospital Cheras?

In Malaysia, G6PD (Glucose-6-Phosphate Dehydrogenase) deficiency is routinely screened, diagnosed, and managed, particularly because it's relatively common among Malaysian newborns.

Diagnosis of G6PD Deficiency in Malaysia

1. Newborn Screening

• Mandatory nationwide under the Ministry of Health Malaysia (MOH) since the 1980s.
• Performed via a heel-prick blood sample within 48-72 hours after birth.
• Sample analysed for G6PD enzyme activity using quantitative assays.
• Babies with low enzyme activity levels are flagged for confirmatory testing.

2. Confirmatory Testing

• Confirmatory quantitative enzyme assay.
• Sometimes includes DNA analysis to detect specific mutations, though not routine.

3. Follow-up

• Diagnosed infants are monitored closely by paediatricians.
• Affected children are given a G6PD alert card and their diagnosis recorded in their personal health record.

Management of G6PD Deficiency in Pantai Hospital Cheras

• General Strategy: Avoidance of Triggers
• No cure, so management is preventive:
  • Avoid oxidative stressors that can cause haemolys.

• Parental Education
  • Parents/caregivers are counselled upon diagnosis.
  • Given a list of prohibited drugs and substances.
  • Taught to recognise signs of haemolysis, e.g. jaundice, dark urine, pallor.

• During Haemolytic Crisis, Immediate medical attention. May require:
  • Hospitalisation
  • Hydration
  • Blood transfusions (if severe anaemia)
  • Treatment of underlying infection if present.

Can children with G6PD deficiency lead a normal and healthy life?

Yes - children with G6PD deficiency can live completely normal lives, healthy lives, provided proper precautions are taken.

What Enables a Normal Life:

1. Avoidance of triggers (medications, foods, chemicals, infections that cause oxidative stress).
2. Parental awareness and education from an early age.
3. Prompt treatment of infections or fever, as infections can precipitate haemolysis.
4. Routine vaccinations and check-ups same as any child.
5. Carrying a G6PD alert card to inform healthcare providers in emergencies.

G6PD deficiency does not affect intelligence, growth, or physical ability. Children can do sports, travel, and attend school like any other child. There is no restriction on physical activity unless a haemolytic crisis is occurring.