Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzyme defect that affects red blood cells. The G6PD enzyme protects red blood cells from oxidative stress, a process that can lead to premature cell destruction. When the enzyme is deficient, red blood cells become vulnerable, leading to hemolytic anemia, often triggered by specific drugs, infections, or foods. Testing for this deficiency is a preventative measure, allowing individuals to manage the condition by avoiding known triggers and preventing potentially severe hemolytic episodes.
Deciding When Testing is Necessary
Testing for G6PD deficiency is primarily performed in three circumstances. In regions where the deficiency is common, particularly parts of Africa, Asia, and the Mediterranean, universal newborn screening is frequently implemented. This early testing, conducted within the first few days of life, identifies affected infants who are at risk for severe neonatal jaundice and potential brain damage.
Testing is also performed when a patient presents with a symptomatic acute hemolytic episode. This sudden destruction of red blood cells often follows exposure to certain oxidative medications, a severe infection, or the ingestion of fava beans. Symptoms of this crisis include unexplained anemia, jaundice, dark urine, and fatigue, prompting a provider to order the G6PD test to find the underlying cause.
A third indication for testing is a known family history of the deficiency. Since G6PD deficiency is an X-linked inherited disorder, testing individuals with affected relatives helps to identify carriers and those who may be asymptomatic. This preventative screening allows for proactive education about which substances to avoid, preventing the first severe crisis.
Primary Screening Methods
The initial step in identifying G6PD deficiency involves rapid, qualitative screening tests designed for speed and convenience. The most widely used method is the Fluorescent Spot Test (FST), which is both affordable and simple to perform. This test works by measuring the production of nicotinamide adenine dinucleotide phosphate (NADPH), the reduced coenzyme that G6PD generates during its normal function.
A blood sample is incubated with the necessary substrates, and a drop is then placed on filter paper and viewed under ultraviolet (UV) light. If the G6PD enzyme is present and functioning normally, the NADPH produced will fluoresce brightly. A sample from a deficient individual will show little to no fluorescence, directly indicating a lack of enzyme activity.
While highly useful for initial screening, the FST is qualitative, meaning it only provides a simple positive or negative result. It can sometimes fail to detect the condition in female carriers who have intermediate enzyme levels. Other screening options, like dye reduction tests, are also used, but they similarly serve as a preliminary step that requires further confirmation if the result is abnormal.
Confirmatory and Advanced Testing
For a definitive diagnosis, particularly when a screening test is ambiguous or when the severity needs to be precisely assessed, a quantitative G6PD assay is considered the gold standard. This test measures the actual amount of G6PD enzyme activity within the red blood cells, typically expressed in international units per gram of hemoglobin (U/g Hb). The spectrophotometric analysis provides a precise numerical value, allowing for classification of the deficiency level.
A consideration for this quantitative testing is the timing of the blood draw. Testing performed immediately following an acute hemolytic crisis can yield a false-negative result. This occurs because the oldest, most deficient red blood cells are destroyed during the crisis, leaving behind a higher proportion of young red blood cells, called reticulocytes. These newer cells contain higher amounts of G6PD activity, temporarily masking the underlying enzyme deficiency.
Providers often delay confirmatory testing until three months after a hemolytic episode has resolved, allowing the red blood cell population to return to a baseline state. Genetic testing, often involving DNA sequencing, is reserved for complex cases, such as identifying specific G6PD variants or when diagnosing female carriers. Molecular analysis can definitively identify the genetic mutation, regardless of the patient’s current red blood cell turnover.
Understanding and Interpreting Test Results
Interpreting the quantitative G6PD test results relies on comparing the measured enzyme activity to a laboratory’s established normal range. Deficiency is generally graded using the World Health Organization’s (WHO) classification system, which categorizes the severity based on the remaining enzyme activity. A severe deficiency is defined as having less than 10% of normal enzyme activity, while a moderate deficiency is between 10% and 60% of normal.
Individuals with severe deficiency typically experience chronic or pronounced episodic hemolysis, whereas those with moderate deficiency usually only have problems when exposed to triggers. It is important to note that a result within the normal range may still be inaccurate if the test was conducted during an acute hemolytic episode.
Upon receiving a deficient result, the next step involves consulting with a hematologist or a physician with expertise in blood disorders. The primary management strategy involves avoiding known trigger substances, including specific antimalarial and sulfa drugs, as well as fava beans. Understanding the specific class of deficiency helps guide the discussion about lifestyle adjustments and the level of vigilance required to prevent future hemolytic episodes.