Neonatal jaundice or Neonatal hyperbilirubinemia,

or Neonatal icterus (from the Greek word ),

attributive adjective:icteric, is a yellowing of the skin and
other tissues of a newborn infant. A bilirubin level of more
than 85 mol/l (5 mg/dL) leads to ajaundiced appearance
in neonates whereas in adults a level of 34 mol/l (2 mg/dL)
is needed for this to occur. In newborns, jaundice is detected
by blanching the skin with pressure applied by a finger so
that it reveals underlying skin and subcutaneous tissue.
[1]
Jaundiced newborns have yellow discoloration of the white
part of the eye, and yellowing of the face, extending down
onto the chest.
Neonatal jaundice can make the newborn sleepy and
interfere with feeding. Extreme jaundice can cause
permanent brain damage from kernicterus.
In neonates, the yellow discoloration of the skin is first noted
in the face and as the bilirubin level rises proceeds caudal to
the trunk and then to the extremities.[2] This condition is
common in newborns affecting over half (5060%) of all
babies in the first week of life.[3]
Infants whose palms and soles are yellow, have serum
bilirubin level over 255 mol/l (15 mg/dL) (more serious
level). Studies have shown that trained examiners
assessment of levels of jaundice show moderate agreement
with icterometer bilirubin measurements.[2] In infants,
jaundice can be measured using invasive or non-invasive
methods.
Causes[edit]
In neonates, jaundice tends to develop because of two
factors - the breakdown of fetal hemoglobin as it is replaced
with adult hemoglobin and the relatively immature
metabolic pathways of the liver, which are unable to
conjugate and so excrete bilirubin as quickly as an adult.
This causes an accumulation of bilirubin in the blood
(hyperbilirubinemia), leading to the symptoms of jaundice.
If the neonatal jaundice does not clear up with
simple phototherapy, other causes such as biliary atresia,
PFIC, bile duct paucity, Alagille syndrome, alpha 1antitrypsin deficiency, and other pediatric liver diseases
should be considered. The evaluation for these will include
blood work and a variety of diagnostic tests. Prolonged
neonatal jaundice is serious and should be followed up
promptly.
Severe neonatal jaundice may indicate the presence of other
conditions contributing to the elevated bilirubin levels, of
which there are a large variety of possibilities (see below).
These should be detected or excluded as part of
the differential diagnosis to prevent the development of
complications. They can be grouped into the following
categories:

Neonatal
jaundice

Unconj
ugated
bilirubi
n

Conjugated
bilirubin

Physiol
ogical
jaundic
e of
Neonat
es

Pathol
ogic

Hemo
lytic

Nonhemoly
tic

Intrin
sic
cause
s

Extrinsi
c
causes

Hepa
tic

Posthepat
ic

Membrane conditions
Spherocytosis
Hereditary elliptocytosis

Systemic conditions

Sepsis

Arteriovenous malformation

Enzyme conditions

Glucose-6-phosphate dehydrogenase
deficiency (also called G6PD deficiency)

Pyruvate kinase deficiency

Globin synthesis defect

sickle cell disease

Alpha-thalassemia, e.g. HbH disease

Extrinsic causes of hemolysis[edit]

Alloimmunity (The neonatal or cord blood gives a

positive direct Coombs test and the maternal blood
gives a positive indirect Coombs test)

Hemolytic disease of the newborn (ABO)[1]

Rh disease[1]

Hemolytic disease of the newborn (antiKell)

Hemolytic disease of the newborn (antiRhc)

Other blood type mismatches

causing hemolytic disease of the newborn
Non-hemolytic causes[edit]

Breast milk jaundice

Cephalohematoma

Polycythemia

Urinary tract infection

Sepsis

Hypothyroidism

Gilbert's syndrome

Crigler-Najjar syndrome

High GI obstruction
Conjugated (Direct)[edit]
Liver causes[edit]

Infections

Sepsis

Hepatitis A

Hepatitis B

TORCH infections

Metabolic

Galactosemia

Alpha-1-antitrypsin deficiency, which is

commonly missed, and must be considered in DDx

Cystic fibrosis

Dubin-Johnson Syndrome

Rotor syndrome

Drugs

Total parenteral nutrition

Idiopathic
Post-liver[edit]

Biliary atresia or bile duct obstruction

Alagille syndrome

Choledochal cyst
Non-organic causes[edit]
Breastfeeding failure jaundice[edit]
"Breastfeeding failure jaundice" or "lack of breastfeeding
jaundice," is caused by insufficient breast milk intake,
[4]
resulting in inadequate quantities of bowel movements to
remove bilirubin from the body. This can usually be
ameliorated by frequent breastfeeding sessions of sufficient
duration to stimulate adequate milk production.

Breast milk jaundice[edit]

Whereas breast feeding jaundice is a mechanical problem,
breast milk jaundice is a biochemical occurrence and the
higher bilirubin possibly acts as an antioxidant. Breast milk
jaundice occurs later in the newborn period, with the
bilirubin level usually peaking in the sixth to 14th days of
life. This late-onset jaundice may develop in up to one third
of healthy breastfed infants.[5]

Unconjugated[edit]
Hemolytic[edit]
Intrinsic causes of hemolysis[edit]

First, at birth, the gut is sterile, and normal gut flora

takes time to establish. The bacteria in the adult gut
convert conjugated bilirubin to stercobilinogen which is
then oxidized to stercobilin and excreted in the stool. In
the absence of sufficient bacteria, the bilirubin is deconjugated by brush border -glucuronidase and
reabsorbed. This process of re-absorption is
called enterohepatic circulation. It has been suggested

that bilirubin uptake in the gut (enterohepatic

circulation) is increased in breast fed babies, possibly as
the result of increased levels of epidermal growth factor
(EGF) in breast milk.[6] Breast milk also contains
glucoronidase which will increase deconjugation and
enterohepatic recirculation of bilirubin.

Second, the breast-milk of some women contains a

metabolite of progesterone called 3-alpha-20-beta
pregnanediol. This substance inhibits the action of the
enzyme uridine diphosphoglucuronic acid
(UDPGA) glucuronyl transferase responsible for
conjugation and subsequent excretion of bilirubin. In
the newborn liver, activity of glucuronyl transferase is
only at 0.1-1% of adult levels, so conjugation of bilirubin
is already reduced. Further inhibition of bilirubin
conjugation leads to increased levels of bilirubin in the
blood.[7] However, these results have not been
supported by subsequent studies.[8]

Third, an enzyme in breast milk called lipoprotein

lipase produces increased concentration of
nonesterified free fatty acids that inhibit hepatic
glucuronyl transferase, which again leads to decreased
conjugation and subsequent excretion of bilirubin.[9]
Physiological jaundice[edit]
Most infants develop visible jaundice due to elevation
of unconjugated bilirubin concentration during their first
week. This common condition is called physiological
jaundice. This pattern of hyperbilirubinemia has been
classified into two functionally distinct periods.
Phase one
1. Term infants - jaundice lasts for about 10 days with
a rapid rise of serum bilirubin up to 204 mol/l
(12 mg/dL).
2. Preterm infants - jaundice lasts for about two
weeks, with a rapid rise of serum bilirubin up to
255 mol/l (15 mg/dL).
Phase two - bilirubin levels decline to about 34 mol/l
(2 mg/dL) for two weeks, eventually mimicking adult
values.
1. Preterm infants - phase two can last more than one
month.
2. Exclusively breastfed infants - phase two can last
more than one month.
Mechanism involved in physiological jaundice are mainly:

Relatively low activity of the

enzyme glucuronosyltransferase which normally
converts unconjugated bilirubin to conjugated bilirubin
that can be excreted into the gastrointestinal tract.
[10]
Before birth, this enzyme is actively down-regulated,
since bilirubin needs to remain unconjugated in order to
cross the placenta to avoid being accumulated in the
fetus.[11] After birth, it takes some time for this enzyme
to gain function.

Shorter life span of fetal red blood cells,[10] being

approximately 80 to 90 days in a full term infant,
[12]
compared to 100 to 120 days in adults.

Relatively low conversion of bilirubin

to urobilinogen by the intestinal flora, resulting in
relatively high absorption of bilirubin back into the
circulation.[10]
Diagnosis[edit]
Clinical Assessment
This method is less accurate and more subjective in
estimating jaundice.
Ingram icterometer: In this method a piece of transparent
plastic known as Ingram icterometer is used. Ingram
icterometer is painted in five transverse strips of graded
yellow lines. The instrument is pressed against the nose and
the yellow colour of the blanched skin is matched with the
graded yellow lines and bilirubin level is assigned.
Transcutaneous bilirubinometer: This is hand held,
portable and rechargeable but expensive and sophisticated.
When pressure is applied to the photoprobe, a xenon tube
generates a strobe light, and this light passes through the
subcutaneous tissue. The reflected light returns through the
second fiber optic bundle to the spectrophotometric module.
The intensity of the yellow color in this light, after correcting
for the hemoglobin, is measured and instantly displayed in
arbitrary units.
Any of the following features characterizes pathological
jaundice:
1. Clinical jaundice appearing in the first 24 hours or
greater than 14 days of life.

2. Increases in the level of total bilirubin by more than

8.5 mol/l (0.5 mg/dL) per hour or (85 mol/l)
5 mg/dL per 24 hours.
3. Total bilirubin more than 331.5 mol/l (19.5 mg/dL)
(hyperbilirubinemia).
4. Direct bilirubin more than 34 mol/l (2.0 mg/dL).
The aim of clinical assessment is to distinguish physiological
from pathological jaundice. The signs which help to
differentiate pathological jaundice of neonates from
physiological jaundice of neonates are the presence
of intrauterine growth restriction, stigma of intrauterine
infections (e.g. cataracts, small head, and enlargement of
the liver and spleen),cephalohematoma, bruising, signs of
bleeding in the brain's ventricles. History of illness is
noteworthy. Family history of jaundice and anemia, family
history of neonatal or early infant death due to liver disease,
maternal illness suggestive of viral infection (fever, rash
or lymphadenopathy), maternal drugs (e.g. sulphonamides,
anti-malarials causing red blood cell destruction in G6PD
deficiency) are suggestive of pathological jaundice in
neonates.[13]
Treatment[edit]
The bilirubin levels for initiative of phototherapy varies
depends on the age and health status of the newborn.
However, any newborn with a total serum bilirubin greater
than 359 mol/l ( 21 mg/dL) should receive phototherapy.[14]
Phototherapy[edit]
The use of phototherapy was first discovered, accidentally,
at Rochford Hospital in Essex, England. The ward sister
(Charge Nurse) of the premature baby unit firmly believed
that the infants under her care benefited from fresh air and
sunlight in the courtyard. Although this led to the first
noticing of jaundice being improved with sunlight, further
studies only progressed when a vial of blood sent for
bilirubin measurement sat on a windowsill in the lab for
several hours. The results indicated a much lower level of
bilirubin than expected based on the patient's visible
jaundice. Further investigation led to the determination that
blue light, wavelength of 420-480nm (peak 458nm), oxidized
the bilirubin to biliverdin, a soluble product that does not
contribute to kernicterus. Although some pediatricians
began using phototherapy in the United Kingdom following
Dr. Cremer's publishing the above facts in the Lancet in
1958, most hospitals only began to regularly use
phototherapy ten years later when an American group
independently made the same discovery.[15][16]

newborn infant undergoing (white light) phototherapy to

treat neonatal jaundice
Infants with neonatal jaundice are treated with colored light
called phototherapy. Physicians randomly assigned 66
infants 35 weeks of gestation to receive phototherapy. After
155 the levels of bilirubin, a yellowish bile pigment that in
excessive amounts causes jaundice, were decreased down
to 0.270.25 mg/dl/h in the blue light. This suggests that
blue light therapy helps reduce high bilirubin levels that
cause neonatal jaundice.[17]
Exposing infants to high levels of colored light changes
trans-bilirubin to the more water soluble cis-form which is
excreted in the bile. Scientists studied 616 capillary blood
samples from jaundiced newborn infants. These samples
were randomly divided into three groups. One group
contained 133 samples and would receive phototherapy with
blue light. Another group contained 202 samples would
receive room light, or white light. The final group contained
215 samples, and were left in a dark room. The total bilirubin
levels were checked at 0, 2, 4, 6, 24, and 48 hours. There
was a significant decrease in bilirubin in the first group
exposed to phototherapy after two hours, but no change
occurred in the white light and dark room group. After 6
hours, there was a significant change in bilirubin level in the
white light group but not the dark room group. It took 48
hours to record a change in the dark room groups bilirubin
level. Phototherapy is the most effective way of breaking
down a neonates bilirubin.[18]
Phototherapy works through a process of isomerization that
changes trans-bilirubin into the water-soluble cis-bilirubin
isomer.[19][20]

In phototherapy, blue light is typically used because it is

more effective at breaking down bilirubin (Amato, Inaebnit,
1991). Two matched groups of newborn infants with jaundice
were exposed to intensive green or blue light phototherapy.
The efficiency of the treatment was measured by the rate of
decline of serum bilirubin, which in excessive amounts
causes jaundice, concentration after 6, 12 and 24 hours of
light exposure. A more rapid response was obtained using
the blue lamps than the green lamps. However, a shorter
phototherapy recovery period was noticed in babies exposed
to the green lamps(1). Green light is not commonly used
because exposure time must be longer to see dramatic
results(1).

Ultraviolet light therapy may increase the risk of skin moles,

in childhood. While an increased number of moles is related
to an increased risk of skin cancer,[21][22][23] it is not ultraviolet
light that is used for treating neonatal jaundice. Rather, it is
simply a specific frequency of blue light that does not carry
these risks.
Increased feedings help move bilirubin through the
neonates metabolic system.[24]
The light can be applied with overhead lamps, which means
that the baby's eyes need to be covered, or with a device
called a Biliblanket, which sits under the baby's clothingclose
to its skin.
Exchange transfusions[edit]
Much like with phototherapy the level at which exchange
transfusions should occur depends on the health status and
age of the newborn. It should however be used for any
newborn with a total serum bilirubin of greater than 428
mol/l ( 25 mg/dL ).[14]
Complications[edit]
Prolonged hyperbilirubinemia (severe jaundice) can result
into chronic bilirubin encephalopathy (kernicterus).[25]
[26]
Quick and accurate treatment of neonatal jaundice helps
to reduce the risk of neonates developing kernicterus.[27]
Infants with kernicterus may have a fever [28] or seizures.
[29]
High pitched crying is an effect of kernicterus. Scientists
used a computer to record and measure cranial nerves 8, 9
and 12 in 50 infants who were divided into two groups
equally depending upon bilirubin concentrations. Of the 50
infants, 43 had tracings of high pitched crying.[30]
Exchange transfusions performed to lower high bilirubin
levels are an aggressive treatment.
[31]
------------------------------------------Hemolytic disease of the newborn, also known
as hemolytic disease of the fetus and
newborn, HDN, HDFN, orerythroblastosis fetalis,[1] is
an alloimmune condition that develops in a fetus, when
the IgG molecules (one of the five main types of antibodies)
produced by the mother pass through the placenta. Among
these antibodies are some which attack the red blood cellsin
the fetal circulation; the red blood cells are broken down and
the fetus can develop reticulocytosis and anemia. This fetal
disease ranges from mild to very severe, and fetal death
from heart failure (hydrops fetalis) can occur. When the
disease is moderate or severe, many erythroblasts are
present in the fetal blood and so these forms of the disease
can be called erythroblastosis fetalis (orerythroblastosis
foetalis).
Symptoms[edit]
Hemolysis leads to elevated bilirubin levels. After delivery
bilirubin is no longer cleared (via the placenta) from the
neonate's blood and the symptoms of jaundice (yellowish
skin and yellow discoloration of the whites of the eyes)
increase within 24 hours after birth. Like any other
severe neonatal jaundice, there is the possibility of acute or
chronickernicterus. Profound anemia can cause highoutput heart failure, with pallor, enlarged liver and/or spleen,
generalized swelling, and respiratory distress. The prenatal
manifestations are known as hydrops fetalis; in severe forms
this can include petechiae and purpura. The infant may
be stillborn or die shortly after birth.[citation needed]

the placenta during pregnancy, or medical procedures

carried out during pregnancy that breach the uterine
wall. In subsequent pregnancies, if there is a similar
incompatibility in the fetus, these antibodies are then
able to cross the placenta into the fetal bloodstream to
attach to the red blood cells and cause hemolysis. In
other words, if a mother has anti-RhD (D being the
major Rhesus antigen) IgG antibodies as a result of
previously carrying a RhD-positive fetus, this antibody
will only affect a fetus with RhD-positive blood.
The woman may have received a therapeutic blood
transfusion. ABO blood group system and the D antigen
of the Rhesus (Rh) blood group system typing are
routine prior to transfusion. Suggestions have been
made that women of child bearing age or young girls
should not be given a transfusion with Rhc-positive
blood or Kell1-positive blood to avoid possible
sensitization, but this would strain the resources of
blood transfusion services, and it is currently considered
uneconomical to screen for these blood groups. HDFN
can also be caused by antibodies to a variety of
other blood group system antigens, but Kell and Rh are
the most frequently encountered.
The third sensitization model can occur in women of

Mother's
Rh
factor

Father's
Rh
factor

Rh
positive

Baby's Rh
factor

Precautions

Rh
positive

Rh positive

None

Rh
negative

Rh
negative

Rh negative

None

Rh
positive

Rh
negative

Could be
Rh positive
or Rh
negative

None

Rh
negative

Rh
positive

Could be
Rh positive
or Rh
negative

Rh immune
globulin
injections

blood type O. The immune response to A and B

antigens, that are widespread in the environment,
usually leads to the production of IgM or IgG anti-A and
anti-B antibodies early in life. Women of blood type O
are more prone than women of types A and B to making
IgG anti-A and anti-B antibodies, and these IgG
antibodies are able to cross the placenta.[citation needed] For
unknown reasons, the incidence of maternal antibodies
against type A and B antigens of the IgG type that could
potentially cause hemolytic disease of the newborn is
greater than the observed incidence of "ABO disease."
About 15% of pregnancies involve a type O mother and
a type A, B, or AB child; only 3% of these pregnancies
result in hemolytic disease due to A/B/O incompatibility.
In contrast to antibodies to A and B antigens, Rhesus
antibodies are generally not produced from exposure to
environmental antigens.
Treatment[edit]

Causes[edit]
Antibodies are produced when the body is exposed to
an antigen foreign to the make-up of the body. If a mother is
exposed to a foreign antigen and produces IgG (as opposed
to IgM which does not cross the placenta), the IgG will target
the antigen, if present in the fetus, and may affect it in
utero and persist after delivery. The three most common
models in which a woman becomes sensitized toward (i.e.,
produces IgG antibodies against) a particular antigen are:

Fetal-maternal hemorrhage can occur due to

abortion, childbirth, ruptures in

Before birth, options for treatment include

intrauterine transfusion or early induction of labor when
pulmonary maturity has been attained, fetal distress is
present, or 35 to 37 weeks of gestation have passed. The
mother may also undergo plasma exchange to reduce the
circulating levels of antibody by as much as 75%.
After birth, treatment depends on the severity of the
condition, but could include temperature stabilization and

monitoring, phototherapy, transfusion with compatible

packed red blood, exchange transfusion with a blood
type compatible with both the infant and the
mother, sodium bicarbonate for correction of acidosis and/or
assisted ventilation.

Rhesus-negative mothers who have had a pregnancy who

are pregnant with a rhesus-positive infant are offered Rh
immune globulin (RhIG) at 28 weeks during pregnancy, at 34
weeks, and within 48 hours after delivery to prevent
sensitization to the D antigen. It works by binding any fetal
red blood cells with the D antigen before the mother is able
to produce an immune response and form anti-D IgG. A
drawback to pre-partum administration of RhIG is that it
causes a positive antibody screen when the mother is
tested, which can be difficult to distinguish from natural
immunological responses that result in antibody production.

Rhesus (Rh) factor is an inherited protein found on the

surface of red blood cells. If your blood has the protein,
you're Rh positive. If your blood lacks the protein, you're Rh
negative.
Rh positive is the most common blood type. Having an Rh
negative blood type is not an illness and usually does not
affect your health. However, it can affect your pregnancy.
Your pregnancy needs special care if you're Rh negative and
your baby's father is Rh positive.
Your health care provider will recommend an Rh factor test
during your first prenatal visit. This test will identify your
blood type and whether your blood cells carry the Rh factor
protein.
The Rh factor test is done during pregnancy to identify a
woman's Rh factor. In some cases, the baby's father might
need an Rh factor test, too.
During pregnancy, problems can occur if you're Rh negative
and the baby you're carrying is Rh positive. Usually, your
blood does not mix with your baby's blood during pregnancy.
However, during delivery or certain times during pregnancy,
a small amount of your baby's blood could come in contact
with your blood.
If you're Rh positive, Rh incompatibility isn't a concern. If
you're Rh negative and your baby is Rh positive, however,
your body might produce proteins called Rh antibodies after
exposure to the baby's red blood cells. The antibodies
produced aren't a problem during the first pregnancy. The
concern is with your next pregnancy. If your next baby is Rh
positive again, your body will produce Rh antibodies that can
cross the placenta and damage the baby's red blood cells.
This could lead to life-threatening anemia, a condition in
which there are not enough red blood cells. If this condition
is not prevented, each Rh positive baby you carry after your
first pregnancy might have severe anemia.
If you're Rh negative, you might need to have another blood
test an antibody screen during your first trimester and
again during week 28 of pregnancy. The antibody screen is
used to detect antibodies to Rh positive blood.
If you haven't started to produce Rh antibodies, you'll need
an injection of a blood product called Rh immune globulin.
The immune globulin prevents your body from producing Rh
antibodies during your pregnancy.
If your baby is born Rh negative, no additional treatment is
needed. If your baby is born Rh positive, you'll need another
injection shortly after delivery.
If you're Rh negative and your baby might be or is Rh
positive, you'll also need an Rh immune globulin injection
after any situation in which your blood could come into
contact with the baby's blood, including:

Miscarriage
Abortion
Ectopic pregnancy when a fertilized eggs
implants somewhere outside the uterus, usually in a
fallopian tube
Molar pregnancy a noncancerous (benign) tumor
that develops in the uterus
Amniocentesis a prenatal test in which a sample
of the fluid that surrounds and protects a baby in the
uterus (amniotic fluid) is removed for testing or treatment

Chorionic villus sampling a prenatal test in which

a sample of the wispy projections that make up most of
the placenta (chorionic villi) is removed for testing
Bleeding during pregnancy
Blunt trauma to the abdomen during pregnancy
Rotation of a baby in a breech position such as
buttocks first before labor
Fetal blood sampling
If the antibody screen shows that you're already producing
antibodies, an injection of Rh immune globulin won't help.
Your baby will be carefully monitored. If necessary, he or she
might be given a blood transfusion through the umbilical
cord during pregnancy or immediately after delivery.
If you're Rh positive, no action is needed.
If you're Rh negative and the baby's father is Rh positive,
there's a potential for your body to produce antibodies that
could harm your baby. If you have vaginal bleeding at any
time during pregnancy, contact your health care provider
immediately. Also, talk with your health care provider about
scheduling an Rh immune globulin injection during your
pregnancy and make sure you remind your health care team
of your Rh status during labor.

Glucose-6-phosphate dehydrogenase deficiency

From Wikipedia, the free encyclopedia
Glucose-6-phosphate dehydrogenase
deficiency (G6PD deficiency) also known as favism (after
the fava bean) is an X-linked recessive genetic condition that
predisposes to hemolysis (spontaneous destruction of red
blood cells) and resultant jaundice in response to a number
of triggers, such as certain foods, illness, or medication. It is
particularly common in people of Mediterranean and African
origin. The condition is characterized by abnormally low
levels of glucose-6-phosphate dehydrogenase, an enzyme
involved in the pentose phosphate pathway that is
especially important in the red blood cell. G6PD deficiency is
the most common human enzyme defect. [1] There is no
specific treatment, other than avoiding known triggers.
Carriers of the G6PD allele appear to be protected to some
extent against malaria, and in some cases dominant males
have shown complete immunity to the disease. This
accounts for the persistence of the allele in certain
populations in that it confers a selective advantage.[2] G6PD
deficiency resulted in 4,100 deaths in 2013 and 3,400
deaths in 1990.[3]
Signs and symptoms[edit]
Most individuals with G6PD deficiency are asymptomatic.
Symptomatic patients are almost exclusively male, due to
the X-linked pattern of inheritance, but female carriers can
be clinically affected due to unfavorable lyonization, where
random inactivation of an X-chromosome in certain cells
creates a population of G6PD-deficient red blood
cells coexisting with normal red cells. A typical female with
one affected X chromosome will show the deficiency in
approximately half of her red blood cells. However, in rare
cases, including double X deficiency, the ratio can be much
more than half, making the individual almost as sensitive as
a male.
Abnormal red blood cell breakdown (hemolysis) in G6PD
deficiency can manifest in a number of ways, including the
following:

Prolonged neonatal jaundice, possibly leading

to kernicterus (arguably the most serious complication
of G6PD deficiency)

Hemolytic crises in response to:

Illness (especially infections)

Certain drugs (see below)

Certain foods, most notably broad beans

Certain chemicals

Diabetic ketoacidosis

Very severe crises can cause acute kidney failure

Favism may be formally defined as a hemolytic response to
the consumption of broad beans. All individuals with favism
show G6PD deficiency. However, not all individuals with
G6PD deficiency show favism. Favism is known to be more
prevalent in infants and children, and G6PD genetic variant
can influence chemical sensitivity.[4] Other than this, the
specifics of the chemical relationship between favism and
G6PD are not well understood.
6-phosphogluconate dehydrogenase (6PGD) deficiency has
similar symptoms and is often mistaken for G6PD deficiency,
as the affected enzyme is within the same pathway,
however these diseases are not linked and can be found
within the same patient.

UDP-Glucuronosyltransferase (UGT), the microsomal enzyme

responsible for glucuronidation reactions, exists as a
superfamily of enzymes. Genetic polymorphism has been
described for 6 of the 16 functional human UGT genes
characterised to date, namely UGT 1A1, 1A6, 1A7, 2B4, 2B7
and 2B15. Since glucuronidation is an essential pathway for
the elimination of a myriad of xenobiotics and endogenous
compounds, genetic polymorphism of UGT is potentially of
toxicological and physiological importance. However,
functional significance has only been convincingly
demonstrated for genetic polymorphism of UGT1A1. Apart
from impaired bilirubin glucuronidation, the mutations
responsible for Gilbert syndrome also affect the elimination
of a limited number of xenobiotics. It has been proposed on
the basis of altered catalytic activity of mutants of UGT 1A6,
1A7 and 2B15 that genetic polymorphism of these forms
may be of toxicological significance, but this is yet to be
proven.
Glucuronidation is the addition of glucuronic acid to a
substrate. Glucuronidation is often involved in xenobiotic
metabolism of substances such as drugs,
pollutants, bilirubin,androgens, estrogens, mineralocorticoid
s, glucocorticoids, fatty acid derivatives, retinoids, and bile
acids. These linkages involve glycosidic bonds.[1]
a phase II detoxification pathway occurring in the liver in whi
ch glucuronic acid is conjugated with toxins. Effectively deto
xifies themajority of commonly prescribed drugs.
genetic polymorphism,
the recurrence within a population of two or more discontinu
ous genetic variants of a specific trait in such proportions th

at they cannot bemaintained simply by mutation. Examples i

nclude the sickle cell trait, the Rh factor, and the blood grou
ps. Compare balanced polymorphism.

KERNICTERUS
The symptoms depend on the stage of kernicterus.
Early stage:
Extreme jaundice
Absent startle reflex
Poor feeding or sucking
Extreme sleepiness (lethargy) and low muscle tone
(hypotonia)
Mid stage:
High-pitched cry
Arched back with neck hyperextended backwards
(high muscle tone/hypertonia)
Bulging fontanel (soft spot)
Seizures
Late stage:
High-frequency hearing loss
Intellectual disability
Muscle rigidity
Speech difficulties
Seizures
Movement disorder
Exams and Tests
A blood test will show a high bilirubin level (greater than 2025 mg/dL).
Note: Normal value ranges may vary slightly among different
laboratories. Talk to your doctor about the meaning of your
specific test results.