MadSci Network: Medicine
Query:

Re: What is the most common disease caused by an enzyme deficiency?

Date: Mon Feb 18 20:22:33 2002
Posted By: June M. Wingert , RM(NRM),Associate Scientist
Area of science: Medicine
ID: 1013381961.Me
Message:

Greetings,
The following will give you the information you need to understand the
most common human enzyme deficiency.
 http://www.rialto.com/g6pd/
Glucose-6-Phosphate Dehydrogenase(G6PD) deficiency is the most common 
human enzyme deficiency; an estimated 400 million people worldwide are 
affected by this enzymopathy (Scriver etal., 1995). One benefit of having 
G6PD deficiency is that it confers a resistance to malaria. G6PD 
deficiency is also sometimes referred to as favism since some G6PD 
deficient individuals are also allergic to fava beans. Individuals with 
reduced G6PD activity are at risk for several pathologies which can be 
potentially serious (even causing death) if they are not properly 
treated.The severity of the pathologies associated with G6PD deficiency 
has prompted researchers to study this condition. Since the discovery of 
G6PD deficiency in 1956, thousands of research papers have been published 
on various aspects of this genetic condition (Carson et al., 1956; 
Beutler, 1994). It is therefore important to learn about G6PD deficiency; 
more specifically, this WEB site will introduce the genetic, 
physiological, molecular, and clinical aspects of this condition.
hen the red blood cell can no longer transport oxygen effectively 
throughout the body, a condition called hemolytic anemia arises. In 
addition to hemolytic anemia, G6PD deficient individuals can expect 
several other clinical manifestations of their condition. These include 
neonatal jaundice, abdominal and/or back pain, dizziness, headache, 
dyspnea (irregular breathing), and palpitations (Cecil, 1992). Only 
neonatal jaundice and hemolytic anemia will be discussed here, since these 
are the two major pathologies associated with G6PD deficiency (see Cecil, 
1992, and Scriver et al., 1995, for a discussion of the other clinical 
manifestations of G6PD deficiency). 

NEONATAL JAUNDICE 
One of the problems experienced by G6PD deficient individuals presents 
itself immediately after birth. Neonatal jaundice is a common condition in 
all newborns, but when it persists, G6PD deficiency is suspected. Neonatal 
jaundice is a yellowish discoloration of the whites of the eyes, skin, and 
mucous membranes caused by deposition of bile salts in these tissues. This 
is a direct result of insufficient activity of the G6PD enzyme in the 
liver. In some cases, the neonatal jaundice is severe enough to cause 
death or permanent neurologic damage (Beutler, 1994). 

HEMOLYTIC ANEMIA 
Hemolytic anemia is another condition which may cause problems for G6PD 
deficient individuals. An anemic response can be induced in affected 
individuals by certain oxidative drugs, fava beans, or infections 
(Beutler, 1994). Death ensues if the hemolytic episode is not properly 
treated. In order to prevent a severe reaction or even death, G6PD 
deficient individuals are prohibited from taking certain drugs; a list of 
drugs that are commonly reported in the literature as inducing hemolysis 
in G6PD deficient individuals appears in Table 2. The common theme shared 
among all of these drugs is that they are oxidizing agents.In G6PD 
deficient individuals, oxidative stress may result in the denaturation, or 
unfolding, of the hemoglobin molecule, the principal oxygen carrying 
molecule inside the red blood cell. This results in the loss of biological 
function with respect to hemoglobin and leads to the inability of the red 
blood cell to effectively transport oxygen throughout the body (Yoshida & 
Beutler, 1986). For reasons still unknown, some G6PD deficient individuals 
do not exhibit drug-induced hemolytic anemia when exposed to certain drugs 
on this list; of course, a physician should always be consulted before any 
medications are taken. 

Primaquine, one of the first anti-malarial drugs, was the first drug to be 
implicated in inducing an anemic response (Carson et al., 1956). All known 
anti-malarial drugs are contra-indicated for G6PD deficient individuals 
(see Table 2); however, in cases of acute uncomplicated malaria, most anti-
malarial drugs can be safely administered (Baird, personal 
correspondence). It is interesting to note that a deficiency in G6PD has 
been shown to sometimes confer a resistance to the malaria-causing 
parasite, Plasmodium falciparum (Scriver et al., 1995). This resistance is 
due to the fact that the parasite selectively infects red blood cells. In 
G6PD deficient red blood cells, an essential metabolite for the survival 
of the parasite is present in insufficient quantities. This is due to 
decreased activity of G6PD within these cells which ultimately leads to 
the death of the parasite (Farid, personal interview). 

In addition to drug-induced hemolytic anemia, there is also fava bean- 
induced hemolytic anemia--called favism. Fava beans were the first, and 
only food product, to be implicated in inducing an anemic response in G6PD 
deficient individuals (Scriver et al., 1995). Inhaling the pollen of the 
fava bean plant can also induce hemolysis in favic individuals. Since some 
G6PD deficient individuals are allergic to fava beans, the deficiency is 
therefore sometimes referred to as favism (THE FAVISM HOMEPAGE). Favism 
has been known to exist since antiquity; the Greek philosopher and 
mathematician Pythagoras was said to have warned his disciples against the 
dangers of eating fava beans (Scriver et al., 1995). The compounds vicine 
and isouramil, abundant in fava beans, are hypothesized to be the 
causative agents of the hemolytic response (Beutler, 1994). 

Outside the areas where favism is prevalent, infection is probably the 
most common cause of hemolysis in subjects with G6PD deficiency. Oxidative 
metabolites produced by numerous bacterial, viral, and rickettsial 
infections have been identified as the cause of the anemic response. 
Particularly important infections that can precipitate a hemolytic episode 
are viral hepatitis, pneumonia, and typhoid fever (Cecil, 1992). 

TREATMENT 
Treatments for neonatal jaundice and hemolytic anemia have existed for 
many years. These treatments insure that the body tissues will be provided 
with enough oxygen by the red blood cells. Infants with prolonged neonatal 
jaundice are placed under special lights, called bili-lights, which 
alleviate the jaundice (Farid, personal interview). When an anemic episode 
occurs, individuals are treated with nasal oxygen and are placed on bed 
rest, which may afford symptomatic relief (Cecil, 1992). Anemic 
individuals are sometimes treated with human haptoglobin products (Ohga et 
al., 1995), and/or blood transfusions (Cecil, 1992). In acute hemolytic 
anemia, patients are administered folic acid (Cecil, 1992). 

Soon, G6PD deficient individuals will no longer have to worry about 
incurring a hemolytic episode in response to fava beans. Techniques are 
currently being developed to genetically engineer the fava bean so that 
the hypothesized causative agents of the hemolytic response are eliminated 
from the bean. This is especially significant since fava beans are an 
important part of the diet in the Middle East, where the frequency of G6PD 
deficiency and favism is high.

Thanks for taking the time to send in a question to the Mad Sci Network.

June Wingert

Mad Scientist



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