GLUCOSE 6-PHOSPHATE

DEHYDROGENASE DEFICIENCY

VY DOAN
NOVEMBER 18TH, 2015

INTRODUCTION OF PATIENT

Age: 56 years old

Gender: Male
Ethnic Background: African American
Admitting Dx: Schizophrenia, Axis II, Hep C, Constipation, GAF 35

CURRENT MEDICAL CONDITIONS

Asthma

Glaucoma
Dyslipidemia
Vitamin D Deficiency
Chronic HCV
Fall Risk
GERD/PUD (Grade IV Esophagitis Cardiac/Fundal Ulcers with Gastritis)
Partial Edentulous
Colostomy Bag Placement S/P Abdominal Surgery and SBO
Chronic Leg Edema
G6PD Deficiency

ALLERGIES

Blue Dye No.9

Aspirin
Sulfamethizoles
Glucose-6-Phosphatase

G6PD DEFICIENCY-ETIOLOGY & INCIDENCE

Most common enzyme deficiency

Affects 400 million people world wide
10% of Males of African Descent in U.S.

High frequency in African, Mediterranean and Asian

variants

Figure 3 (A) Worldwide prevalence of G6PD deficiency according to the World Health
Organization (1989).

In 1989

Anna L. Peters, and Cornelis J.F. Van Noorden J Histochem

Cytochem 2009;57:1003-1011
Copyright by The Histochemical Society

In 2009

In 2009

MALARIA-WHATS THE LINK?

Rare in the U.S.
About 1,500 cases of malaria are diagnosed in the United States each year.
travelers and immigrants returning from countries where malaria transmission occurs (sub-Saharan

Africa and South Asia)

Worldwide, an estimated 198 million cases of malaria occurred in 2013
500,000 people died, mostly children in the African Region.

Caused by a bite from a mosquito infected with parasites

Most common form: Plasmodium Vivax (Africa)
Anopheles Mosquito
Source: Center for Disease Control and Prevention

ETIOLOGY
X-linked recessive disorder
Similar to hemophilia and color
blindness
Gene is maternal
Females are carriers males more
susceptible to abnormality
Females may be symptomatic
Homozygous (deficient) or if
inactivation of normal X chromosome
occurs.

NUTRIGENOMICS

140 known G6PD mutations

One missense mutation, or one amino acid

change in sequence of G6PD protein from

Variant B

VARIANTS

A+
High enzyme
levels
No hemolysis

A Lower Enzyme
levels
Acute int.
hemolysis
Class II*
(WHO)

G6PD
Mediterranean A More severe
than in other
G6PD A- alleles
Fava bean
hemolysis
Class III*
(WHO)

Most Common*

B
Wild type allele
(normal variant)

CLASSES (WHO)
G6PD Deficiency Class

G6PD Activity (% normal)

Phenotype

Class I

<10

Chronic nonspherocytic
hemolytic anemia

Class II

<10

Intermittent hemolysis

Class III

10-60

Class IV

60-150

Class V

>150

Source: http://www.pathophys.org/g6pd/

Normal Activity

PATHOPHYSIOLOGY
G6PD: enzyme for first step of the
Pentose Phosphate Pathway (HMP
shunt)
G6PD reduces NADP to
NADPH while oxidizing G6P
(rate-limiting step of the
pathway).
HMP Pathway : metabolic pathway
NADPH **
Phosphorylated sugars F6P and
G3P
CO2 and H+

*ROS=reactive
oxygen species

PATHOPHYSIOLOGY
Important product of PPP

What it is

Product per glucose entering

Importance

NADPH (nicotinamide
adenine dinucleotide
phosphate)

An electron carrier, the

+
reduced form of NADP

2 NADPH / 1 glucose

Used by the cell for

reductive reactions (FA
synthesis), protects

against oxidation
Fructose-6-phosphate
(F6P)

6 carbon sugar with

phosphate group

2 F6P / 3 glucose

Glyceraldehyde-3phosphate (G3P)

3 carbon sugar with

phosphate group

1 G3P / 3 glucose

Source: http://www.pathophys.org/g6pd/

Continue using for energy

or precursor for
biosynthesis

PATHOPHYSIOLOGY
GSH (Glutathione) converts
hydrogen peroxide and
organic hydroperoxides
(very reactive compounds)
into stable compounds
NADPH needed to
regenerate GSH from GSSG
(Oxidized glutathione)

WHAT DOES THIS ALL MEAN?

HMP Pathway only source of NADPH for

erythrocytes
GSH

Acute
Hemolysis

Peroxides

no protection from
reactive oxygen
species damage
to the cell membrane

PATHOPHYSIOLOGY

Oxidative
stress

Denatured
Hb

Heinz Bodies

Intravascular
hemolysis

Release
of
heme

Hyperbilirubinemia

Kernicterus

DIAGNOSIS
Quantitative spectrophotometric analysis
Rapid fluorescent spot test (Buetler) detects generation of NADPH from NADP

Fails to fluorescent under UV light test is positive

Quick results; inexpensive
Primarily done in children and neonates but can be done in adults if incidence of

hemolytic anemia occurs in reaction to oxidative drug or ingestion of fava beans

Not done routinely in the US
WHO recommends screening of all newborns in populations with a prevalence of

3-5 percent or more in males. (2015).

BUETLER TEST
Leslie, et. al Malaria Journal 2013 12:230 doi:10.1186/1475-2875-12-230

SIGNS + SYMPTOMS
Mostly Asymptomatic
Can include...
Neonatal Jaundice
Acute hemolytic anemia (uncommon)
10% (4 out of 40) developed acute hemolysis developed acute hemolysis in exposure to

oxidative drugs (Dapsone) -Serpa,Villareal-Williams, Giordano, 2010

Similar to other anemias fatigue, dizziness, possible hypotension

Chills, fever, pain in the back and abdomen, prostration, and shock.
Severe hemolysis jaundice and splenomegaly
Hemoglobinuria red or reddish-brown urine

PATIENT DIET

Mechanical Soft Advanced Diet (artificial sweeteners

only)
Estimated Needs:
2100-2500 kcals
67 gm (0.8 gm protein/kg body weight)
2.5-2.9 L (30-35 mL/kg)

PATIENT MEDICATIONS
Treatment of...

Medication

DNI

Vitamin
Deficiencies

MVM w/ Iron

N/V/C/D, abs. of Thyroxine (T4)

Asorbic Acid

**CAUTION: G6PD-deficit cause hemolytic anemia with high dose

Choleciferol

BUN/Creat, wt. dry mouth

Opthalmic

Brimonidine Tartrate

HTN, palpitations

Asthma

Montelukast

Dyspepsia, diarrhea

Constipation

Lactulose

High fiber diet w/ 1.5-2.0 L fuid/day

N/V/D, belching, cramps, Gluc

Docusate Sodium (DOK)

Same diet with Lactulose, bitter taste, throat irritation, N/D, Gluc

Bipolar Disorder

Lithium

thirst, wt, fatigue, diabetes, WBC, platelets

Schizophrenia

Olanzapine

appetite, wt, obesity, thirst, dry mouth, N/V/C, diabetes, drowsiness, Gluc,
TG, WBC

GERD

Omeprazole

*May abs of Fe., B12, and C (by 61%), N/D, ab pain

Depression

Paroxetine

appetite, wt, dry mouth, taste changes, N/V/C/D, Hb, Hct, Na, Chol,
WBC

DISCUSSION

Why are they normal?

Compensation by increased erythrocyte

production and/or removal of the oxidant stress.

AVOIDANCE IS KEY!

SUBJECTIVE (10/12/15)

Denies chewing/swallowing or GI complications

Pt. currently on colostomy bag d/t abdominal surgery

Denies any knowledge or family hx of G6PD deficiency
Educated on overview of disease, signs and symptoms

PES STATEMENT

Patient was not ready for diet/lifestyle changes related to

impaired cognitive abilities as evidenced by global assessment

functionality 30, inability to manage self-care and inability to
understand required changes.

INTERVENTIONS & RECOMMENDATIONS

Avoidance of sulfa drugs (listed on allergies)

and fava beans

Legumes (precautionary measure) and fava

beans to be put in Compnutrition

Closely monitor CBC for any significant

changes

Take out artificial sweeteners, although no

contraindication with G6PD deficiency

found.

PROGNOSIS

G6PD deficiency considered mild and benign condition

Main concern: avoidance of sulfa drugs, anti-malarials

(Primoquine), fava beans, moth balls, or legumes

Possible outcomes: acute kidney failure from ischemia but

is a rare complication.

SIGNIFICANT FINDINGS: MERGING THE LINK

Cancer Biomarker

G6PD plays crucial role in survival, proliferation, and metastasis of cancer cells
Recent studies showing G6PD inhibitors in cancer treatment (Zhang, et. al, 2014).
Reduce risk of coronary diseases

Cholesterol synthesis, Reductive Stress (Hecker, et. al 2012).

Protective against Malaria
Much like sickle cell anemia, G6PD has an innate ability to protect against malaria

infection
Females do not benefit from this protection (Leslie, et. al 2010).

GLOSSARY
1. Malaria: mosquito borne disease caused by a parasite. Signs and symptoms include fever,

chills, and flu-like illness. Estimated 198 million cases world wide of malaria, 500,000 deaths,
mostly effecting children in the African Region (CDC, 2015).
2. Hemophilia: Condition where the blood does not clot normally, lack of coagulation factor
(Mayo Clinic, 2015).
3. Kernicterus: rare neurological condition that occurs in some newborns with severe jaundice.
Complications can lead to brain damage and hearing loss. It is caused by very high levels of
bilirubin and is detected and seen in parts of the brain on autopsy (Medline Plus 2013).
4. Chronic nonspherocytic hemolytic anemia: caused by a very small subset of the G6PD
mutations which cause a more severe phenotype due to very low G6PD activity (Klowak, et.
al, 2015).

REFERENCES
1. Cappellini, M., & Fiorelli, MD, G. (January 2008). Glucose-6-Phosphate-Dehydrogenase Deficiency. The Lancet, 371(9606), 64-74. doi:10.1016/S0140-6736(08)60073-2
2. Center for Disease Control and Prevention. (2015, August 17). Retrieved October 30, 2015, from http://www.cdc.gov/malaria/
3. Herndon, J. (2012, June 14). G6PD Deficiency (B. Spriggs, MD, MPH, Ed.). Retrieved October 21, 2015.

4. Hecker, P., Mapanga, R., Kimar, C., Ribeiro, R., Brown, B., O'connell, K., . . . Stanley, W. (2012). Effects of glucose-6-phosphate dehydrogenase deficiency on the metabolic and cardiac
responses to obesogenic or high-fructose diets. AJP: Endocrinology and Metabolism.
5. Howes, R., Piel, F., Patil, A., Nyangiri, O., Gething, P., Dewi, M., . . . Hay, S. (2012). G6PD Deficiency Prevalence and Estimates of Affected Populations in Malaria Endemic Countries:
A Geostatistical Model-Based Map. Plos Med PLoS Medicine.
6. Kaplan, M., & Hammerman, C. (2010). Glucose-6-phosphate dehydrogenase deficiency and severe neonatal hyperbilirubinemia: A complexity of interactions between genes and
environment. Seminars in Fetal and Neonatal Medicine, 148-156.
7. Klowak, J., Wong, E., Verhovsek, MD FRCPC, M., & Chaudhry, S. (2015). Glucose-6 phosphate dehydrogenase deficiency. Retrieved November 16, 2015, from
http://www.pathophys.org/g6pd/
8. Leslie, T., Briceo, M., Mayan, I., Mohammed, N., Klinkenberg, E., Sibley, C, Rowland, M. (2010). The Impact of Phenotypic and Genotypic G6PD Deficiency on Risk of
Plasmodium vivax Infection: A Case-Control Study amongst Afghan Refugees in Pakistan. Plos Med PLoS Medicine.
9. WHO Working Group. Glucose-6-phosphate dehydrogenase deficiency. Bull World Health Organ. 1989;67:60111.

10. Zhang, C., Zhang, Z., Zhu, Y., & Qin, S. (2014). Glucose-6-phosphate Dehydrogenase: A Biomarker and Potential Therapeutic Target for Cancer. Anti-Cancer Agents in Medicinal
Chemistry ACAMC, 280-289.