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• Draw up a diagnostic and treatment plan
on the basis of the probability diagnosis?
• Would it make any difference to your
differential diagnosis if the child was 1 day
old rather than 3 day old ? OR 10 day old?
Give reasons for your answer.
Learning Objectives
n ro uction
Jaundice occurs in approximately 60% of newborns but
only a few will require investigation and treatment.
Draw up a
diagnostic on the
basis of the
probability
diagnosis?
A transcutaneous bilirubinometer:
Serum bilirubin:
LFTs:
Aspartate aminotransferase (ASAT ) and
alanine aminotransferase (ALAT ) levels are
elevated in:
Hepatocellular disease.
Alkaline phosphatase and γ-
glutamyltransferase(GGT) levels are often
elevated in:
cholestatic disease.
Toxoplasmosis, rubella, herpes
simplex
Surface swabs including umbilicus,
throat swabs, urine culture, blood
culture, lumbar puncture, CXR.
Infection screen:
Reducing substance in urine:
Screening test for
galactosaemia
Thyroid function tests:
Blood type and Rh determination in mother and
infant.
Reticulocyte count.
Haemoglobin and haematocrit values.
Direct coombs test
Peripheral blood film for erythrocyte morphology.
Red cell enzyme assays: glucose-6-phosphate
dehydrogenase activity (G6PD deficiency), pyruvate
kinase deficiency.
Hemolytic work-up :
Ultrasound, radionuclide scan, liver biopsy
may be required for cholestatic jaundice in
the differentiation between hepatitis and
biliary atresia.
Draw up a treatment plan on the
basis of the probability diagnosis?
Doctors, nurses, and family members will
watch for signs of jaundice at the hospital
and after the newborn goes home.
When treatment is needed,
the type will depend on:
•The baby's bilirubin level.
•How fast the level has been
rising.
•Whether the baby was born
early .
IF
Physiological
jaundice :
The type seen in most newborns -- does not require
aggressive treatment.
with frequent feedings the baby often (up to 12 times a
day) to encourage frequent bowel movements. These help
remove bilirubin through the stools. And exposure to
indirect sunlight at home.
It will typically disappear in a few days (within 1 -2wk.)
Doctors may test the baby's bilirubin levels during that
time to make sure it has not gotten worse.
Phototherapy
treatment
Exchange
transfusion
Intravenous
immunoglobulin
IF baby has more severe jaundice, she/he may need
treatment including:
When unconjugated bilirubin is > 12
mg/dl (> 205.2 μmol/L)
And when unconjugated bilirubin is
> 15 mg/dl at 25 to 48 h, 18 mg/dl at
49 to 72 h, and 20 mg/dl at > 72 h
Phototherapy is not indicated for
conjugated hyperbilirubinemia.
Indication:
Phototherapy treatment
Phototherapy is the use of light to photoisomerize
unconjugated bilirubin into forms that are more water-
soluble and can be excreted rapidly by the liver and
kidney.
 It provides definitive treatment of neonatal
hyperbilirubinemia and prevention of kernicterus.
Phototherapy treatment
Treatment with phototherapy is
successful for almost all infants.
Side effects:
• Phototherapy is very safe, but it can have
temporary side effects, including a skin rash and
loose bowel movements.
• Overheating and dehydration can occur if the infant
does not get enough breast milk or formula.
Phototherapy is stopped when bilirubin levels decline
to a safe level.
is done to prevent or minimize
bilirubin-related brain damage.
The transfusion replaces an infant's
blood with donated blood in an attempt
to quickly lower bilirubin levels.
performed in infants who have not
responded to other treatments
Exchange transfusion :
oBilirubin >340 micromol/L
oWho have signs of or are at significant
neurologic risk of bilirubin toxicity
Indications:
Risks of exchange transfusions:
(uncommon) include:
bradycardia
vasospasm
air embolism
infection
thrombosis
If a baby have different blood
types, may get immunoglobulin (a
blood protein) through a needle
into a vein.
This can help her treat her jaundice
so that she’s less likely to need an
exchange transfusion.
Intravenous immunoglobulin
(also called IVIg):
Would it make any
difference to your
differential diagnosis if
the child was 1 day old
rather than 3 day old ?
OR 10 day old? Give
reasons for your
answer.
Best classified by age of onset and
duration:
1.Early: within 24 hrs of life.
2.Intermediate: 2 days to 2
weeks.
3.Late: persists for >2 weeks.
Early:
Haemolytic causes: Rh incompatibility- ABO incompatibility-
G6PD deficiency
Congenital infection .
 Increased haemolysis due to haematoma.
 Maternal autoimmune haemolytic anaemia: eg, systemic lupus
erythematosus.
Crigler-Najjar syndrome.
 Gilbert's syndrome.
• Physiological jaundice
• Breast milk jaundice (inadequate
intake)
• Sepsis
• Haemolysis
• Crigler-Najjar syndrome (glucuronyl
transferase absent/reduced)
• Polycythaemia
• Hypothyroidism, hypopituitarism.
• Galactosaemia.
Intermediate:
• Conjugated (dark urine, pale stools):
– Bile duct obstruction
– Biliary atresia
– Neonatal hepatitis
• Unconjugated:
– Physiological (rare).
– Breast milk jaundice
– Infection
– Hypothyroidism
References
• Kliegman Book.
• Merck Manual
• http://www.health.vic.gov.au/neonatalhandbook/conditions/jaundice-in-
neonates.htm
• http://www.nlm.nih.gov/medlineplus/ency/article/001559.htm
• http://www.emedicinehealth.com
• http://www.healthline.com
• http://www.patient.co.uk/doctor/neonatal-jaundice-pro
• http://www.nhs.uk/conditions/jaundice-newborn/pages/treatment.aspx
Than
k you

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Yellow Baby

  • 2. • Draw up a diagnostic and treatment plan on the basis of the probability diagnosis? • Would it make any difference to your differential diagnosis if the child was 1 day old rather than 3 day old ? OR 10 day old? Give reasons for your answer. Learning Objectives
  • 3. n ro uction Jaundice occurs in approximately 60% of newborns but only a few will require investigation and treatment.
  • 4. Draw up a diagnostic on the basis of the probability diagnosis?
  • 7. LFTs: Aspartate aminotransferase (ASAT ) and alanine aminotransferase (ALAT ) levels are elevated in: Hepatocellular disease. Alkaline phosphatase and γ- glutamyltransferase(GGT) levels are often elevated in: cholestatic disease.
  • 8. Toxoplasmosis, rubella, herpes simplex Surface swabs including umbilicus, throat swabs, urine culture, blood culture, lumbar puncture, CXR. Infection screen:
  • 9. Reducing substance in urine: Screening test for galactosaemia
  • 11. Blood type and Rh determination in mother and infant. Reticulocyte count. Haemoglobin and haematocrit values. Direct coombs test Peripheral blood film for erythrocyte morphology. Red cell enzyme assays: glucose-6-phosphate dehydrogenase activity (G6PD deficiency), pyruvate kinase deficiency. Hemolytic work-up :
  • 12. Ultrasound, radionuclide scan, liver biopsy may be required for cholestatic jaundice in the differentiation between hepatitis and biliary atresia.
  • 13. Draw up a treatment plan on the basis of the probability diagnosis?
  • 14. Doctors, nurses, and family members will watch for signs of jaundice at the hospital and after the newborn goes home.
  • 15. When treatment is needed, the type will depend on: •The baby's bilirubin level. •How fast the level has been rising. •Whether the baby was born early .
  • 16. IF Physiological jaundice : The type seen in most newborns -- does not require aggressive treatment. with frequent feedings the baby often (up to 12 times a day) to encourage frequent bowel movements. These help remove bilirubin through the stools. And exposure to indirect sunlight at home. It will typically disappear in a few days (within 1 -2wk.) Doctors may test the baby's bilirubin levels during that time to make sure it has not gotten worse.
  • 17. Phototherapy treatment Exchange transfusion Intravenous immunoglobulin IF baby has more severe jaundice, she/he may need treatment including:
  • 18. When unconjugated bilirubin is > 12 mg/dl (> 205.2 μmol/L) And when unconjugated bilirubin is > 15 mg/dl at 25 to 48 h, 18 mg/dl at 49 to 72 h, and 20 mg/dl at > 72 h Phototherapy is not indicated for conjugated hyperbilirubinemia. Indication: Phototherapy treatment
  • 19.
  • 20. Phototherapy is the use of light to photoisomerize unconjugated bilirubin into forms that are more water- soluble and can be excreted rapidly by the liver and kidney.  It provides definitive treatment of neonatal hyperbilirubinemia and prevention of kernicterus. Phototherapy treatment Treatment with phototherapy is successful for almost all infants.
  • 21. Side effects: • Phototherapy is very safe, but it can have temporary side effects, including a skin rash and loose bowel movements. • Overheating and dehydration can occur if the infant does not get enough breast milk or formula. Phototherapy is stopped when bilirubin levels decline to a safe level.
  • 22. is done to prevent or minimize bilirubin-related brain damage. The transfusion replaces an infant's blood with donated blood in an attempt to quickly lower bilirubin levels. performed in infants who have not responded to other treatments Exchange transfusion :
  • 23. oBilirubin >340 micromol/L oWho have signs of or are at significant neurologic risk of bilirubin toxicity Indications: Risks of exchange transfusions: (uncommon) include: bradycardia vasospasm air embolism infection thrombosis
  • 24. If a baby have different blood types, may get immunoglobulin (a blood protein) through a needle into a vein. This can help her treat her jaundice so that she’s less likely to need an exchange transfusion. Intravenous immunoglobulin (also called IVIg):
  • 25. Would it make any difference to your differential diagnosis if the child was 1 day old rather than 3 day old ? OR 10 day old? Give reasons for your answer.
  • 26. Best classified by age of onset and duration: 1.Early: within 24 hrs of life. 2.Intermediate: 2 days to 2 weeks. 3.Late: persists for >2 weeks.
  • 27. Early: Haemolytic causes: Rh incompatibility- ABO incompatibility- G6PD deficiency Congenital infection .  Increased haemolysis due to haematoma.  Maternal autoimmune haemolytic anaemia: eg, systemic lupus erythematosus. Crigler-Najjar syndrome.  Gilbert's syndrome.
  • 28. • Physiological jaundice • Breast milk jaundice (inadequate intake) • Sepsis • Haemolysis • Crigler-Najjar syndrome (glucuronyl transferase absent/reduced) • Polycythaemia • Hypothyroidism, hypopituitarism. • Galactosaemia. Intermediate:
  • 29. • Conjugated (dark urine, pale stools): – Bile duct obstruction – Biliary atresia – Neonatal hepatitis • Unconjugated: – Physiological (rare). – Breast milk jaundice – Infection – Hypothyroidism
  • 30.
  • 31. References • Kliegman Book. • Merck Manual • http://www.health.vic.gov.au/neonatalhandbook/conditions/jaundice-in- neonates.htm • http://www.nlm.nih.gov/medlineplus/ency/article/001559.htm • http://www.emedicinehealth.com • http://www.healthline.com • http://www.patient.co.uk/doctor/neonatal-jaundice-pro • http://www.nhs.uk/conditions/jaundice-newborn/pages/treatment.aspx

Notas del editor

  1. A bilirubin concentration > 10 mg/dL (> 170 μmol/L) in preterm infants or > 18 mg/dL in term infants warrants additional testing, including Hct, blood smear, reticulocyte count, direct Coombs' test, TSB and direct serum bilirubin concentrations, and blood type and Rh group of the infant and mother.  http://emedicine.medscape.com/article/974786-workup#a0719 Other tests, such as blood, urine, and CSF cultures to detect sepsis and measurement of RBC enzyme levels to detect unusual causes of hemolysis, may be indicated by the history and physical examination. Such tests also may be indicated for any neonates with an initial bilirubin level > 25 mg/dL (> 428μmol/L).  Investigations Usually, a TOTAL serum bilirubin level is the only testing required in a moderately jaundiced infant who presents on the second or third day of life and is otherwise well. Further investigation is essential for any baby who is also unwell, presents in the first 24 hours or has prolonged (after 10 days) jaundice.
  2. readings are taken by gently pressing the sensor on the infants' forehead or sternum, all device functions can be controlled using a colour touchscreen. Transcutaneous bilirubinometry can be performed using handheld devices that incorporate sophisticated optical algorithms. Use of such devices has been shown to reduce the need for blood sampling in infants with jaundice.[21]However, they cannot be used to monitor the progress of phototherapy.[22] Transcutaneous bilirubinometry performs better than visual assessment. The latter is not a reliable technique for estimating levels of bilirubin,[23] but the complete absence of jaundice as judged by the eye in good lighting conditions has quite high accuracy as far as predicting which infants are unlikely to develop high total serum bilirubin levels.[24] In infants with mild jaundice, transcutaneous bilirubinometry may be all that is needed to assure that total bilirubin levels are safely below those requiring intervention. In infants with moderate jaundice, transcutaneous bilirubinometry may be useful in selecting patients who require phlebotomy or capillary blood sampling for serum bilirubin measurement. In infants with extreme jaundice, transcutaneous bilirubinometry may be a useful tool to fast-track such infants to rapid and aggressive therapy. Usually, a total serum bilirubin level test is the only one required in an infant with moderate jaundice who presents on the typical second or third day of life without a history and physical findings suggestive of a pathologic process. Measurement of bilirubin fractions (conjugated vs unconjugated) in serum is not usually required in infants who present as described above. However, in infants who have hepatosplenomegaly, petechiae, thrombocytopenia, or other findings suggestive of hepatobiliary disease, metabolic disorder, or congenital infection, early measurement of bilirubin fractions is suggested. The same may apply to infants who remain jaundiced beyond the first 7-10 days of life, and to infants whose total serum bilirubin levels repeatedly rebound following treatment. Additional studies may be indicated in the following situations: Infants who present with jaundice on the first or after the third day of life Infants who are anemic at birth Infants who otherwise appear ill Infants in whom serum bilirubin levels are elevated enough to trigger treatment Infants in whom significant jaundice persists beyond the first 2 weeks of life Infants in whom family, maternal, pregnancy, or case histories suggest the possibility of a pathologic process Infants in whom physical examination reveals findings not explained by simple physiologic hyperbilirubinemia In addition to total serum bilirubin levels, other suggested studies may include the following, particularly if the rate of rise or the absolute bilirubin concentration is approaching the need for phototherapy: Blood type and Rh determination in mother and infant Direct antiglobulin test (DAT) in the infant (direct Coombs test) Hemoglobin and hematocrit values Serum albumin levels: This appears to be a useful adjunct in evaluating risk of toxicity levels because albumin binds bilirubin in a ratio of 1:1 at the primary high-affinity binding site. Nomogram for hour-specific bilirubin values: This is a useful tool for predicting, either before or at the time of hospital discharge, which infants are likely to develop high serum bilirubin values. Infants identified in this manner require close follow-up monitoring and repeated bilirubin measurements. The predictive ability has been shown both for bilirubin values measured in serum and for values measured transcutaneously. The nomogram has also been shown to work well for DAT-positive infants with AB0 incompatibility.[25] A positive DAT test result did not add any value to the clinical management of these infants beyond that already obtained by an hour-specific bilirubin value plotted onto the nomogram. Measurement of end-tidal carbon monoxide in breath: End-tidal carbon monoxide in breath (ETCO) may be used as an index of bilirubin production. Measurement of ETCO may assist in identifying individuals with increased bilirubin production and, thus, at increased risk of developing high bilirubin levels. An apparatus has been developed that makes measuring ETCO simple (CoSenseTM ETCO Monitor, Capnia, Palo Alto, CA, USA). readings are taken by gently pressing the sensor on the infants' forehead or sternum, all device functions can be controlled using a colour touchscreen.
  3.  Aspartate aminotransferase (ASAT ) and alanine aminotransferase (ALAT ) levels are elevated in hepatocellular disease. Alkaline phosphatase and γ-glutamyltransferase(GGT) levels are often elevated in cholestatic disease. Liver function tests: Aspartate aminotransferase (ASAT or SGOT) andalanine aminotransferase (ALAT or SGPT) levels are elevated in hepatocellular disease. Alkaline phosphatase and γ-glutamyltransferase(GGT) levels are often elevated in cholestatic disease. A γ-GT/ALAT ratio of more than 1 is strongly suggestive of biliary obstruction. However, it does not distinguish between intrahepatic and extrahepatic cholestasis.
  4. Infection screen (must be excluded in any baby who is unwell or presents in the first 24 hours or after day 3): toxoplasmosis, rubella, CMV and herpes simplex (TORCH) congenital infection screen, surface swabs including umbilicus, throat swabs, urine culture, blood culture, lumbar puncture, CXR. Tests for viral and/or parasitic infection: These may be indicated in infants with hepatosplenomegaly, petechiae, thrombocytopenia, or other evidence of hepatocellular disease.
  5. galactose-1-phosphate uridyltransferase deficiency, GALT deficiency, GALT,galactose diabetes Although it is a rare inherited disease it is among the most common carbohydratemetabolism disorders. It can be a life-threatening illness during the newborn period.[1] Thecardinal features are hepatomegaly Reducing substance in urine: This is a useful screening test for galactosemia, provided the infant has received sufficient quantities of milk. Definition This is a screening test to detect various substances in the urine that chemically react with an indicator metallic dye called cupric sulfate. The most common reducing substances examined include glucose or galactose. Alternative Names Clinitest How the test is performed Collect a "clean-catch" (midstream) urine sample. To do so, men and boys should wipe clean the head of the penis. Women and girls need to wash the area between the lips of the vagina with soapy water and rinse well. As you start to urinate, allow a small amount to fall into the toilet bowl (this clears the urethra of contaminants). Then, in a clean container, catch about 1 to 2 ounces of urine and remove the container from the urine stream. Give the container to the health care provider or assistant. For an infant, thoroughly wash the area around the urethra. Open a urine collection bag (a plastic bag with an adhesive paper on one end), and place it on your infant. For males, the entire penis can be placed in the bag and the adhesive attached to the skin. For females, the bag is placed over the labia. Place a diaper over the infant (bag and all). Check your baby frequently and remove the bag after the infant has urinated into it. For active infants, this procedure may take a couple of attempts -- lively infants can displace the bag, causing an inability to obtain the specimen. The urine is drained into a container for transport back to the health care provider. A Clinitest tablet is placed in a sample of the urine. If urinary reducing substances (glucose, galactose, or other reducing substances) are present, the urine will turn blue. screening test for galactosaemia (provided the infant has received sufficient quantities of milk).
  6. Blood type and Rh determination in mother and infant Direct antiglobulin test (DAT) in the infant (direct Coombs test) Hemoglobin and hematocrit values Serum albumin levels: This appears to be a useful adjunct in evaluating risk of toxicity levels because albumin binds bilirubin in a ratio of 1:1 at the primary high-affinity binding site. Nomogram for hour-specific bilirubin values: This is a useful tool for predicting, either before or at the time of hospital discharge, which infants are likely to develop high serum bilirubin values. Infants identified in this manner require close follow-up monitoring and repeated bilirubin measurements. The predictive ability has been shown both for bilirubin values measured in serum and for values measured transcutaneously. The nomogram has also been shown to work well for DAT-positive infants with AB0 incompatibility.[25] A positive DAT test result did not add any value to the clinical management of these infants beyond that already obtained by an hour-specific bilirubin value plotted onto the nomogram. Measurement of end-tidal carbon monoxide in breath: End-tidal carbon monoxide in breath (ETCO) may be used as an index of bilirubin production. Measurement of ETCO may assist in identifying individuals with increased bilirubin production and, thus, at increased risk of developing high bilirubin levels. An apparatus has been developed that makes measuring ETCO simple (CoSenseTM ETCO Monitor, Capnia, Palo Alto, CA, USA). Peripheral blood film for erythrocyte morphology Reticulocyte count Conjugated bilirubin levels: Measuring bilirubin fractions may be indicated in the circumstances described above. Note that direct bilirubin measurements are often inaccurate, are subject to significant interlaboratory and intralaboratory variation, and are generally not a sensitive tool for diagnosingcholestasis unless repeated measurements confirm the presence of an elevated conjugated bilirubin. Liver function tests: Aspartate aminotransferase (ASAT or SGOT) andalanine aminotransferase (ALAT or SGPT) levels are elevated in hepatocellular disease. Alkaline phosphatase and γ-glutamyltransferase(GGT) levels are often elevated in cholestatic disease. A γ-GT/ALAT ratio of more than 1 is strongly suggestive of biliary obstruction. However, it does not distinguish between intrahepatic and extrahepatic cholestasis. Tests for viral and/or parasitic infection: These may be indicated in infants with hepatosplenomegaly, petechiae, thrombocytopenia, or other evidence of hepatocellular disease. Reducing substance in urine: This is a useful screening test for galactosemia, provided the infant has received sufficient quantities of milk. Blood gas measurements: The risk of bilirubin CNS toxicity is increased in acidosis, particularly respiratory acidosis. Bilirubin-binding tests: Although they are interesting research tools, these tests have not found widespread use in clinical practice. Although elevated levels of unbound ("free") bilirubin are associated with an increased risk of bilirubin encephalopathy, unbound bilirubin is but one of several factors that mediate/modulate bilirubin toxicity. Thyroid function tests  
  7. Ultrasonography: Ultrasonography of the liver and bile ducts is warranted in infants with laboratory or clinical signs of cholestatic disease. Radionuclide scanning: A radionuclide liver scan for uptake of hepatoiminodiacetic acid (HIDA) is indicated if extrahepatic biliary atresia is suspected. At the author's institution, patients are pretreated with phenobarbital 5 mg/kg/d for 3-4 days before performing the scan.
  8. Intravenous immunoglobulin (also called IVIg). If you and your baby have different blood types, your baby may get immunoglobulin (a blood protein) through a needle into a vein. This can help her treat her jaundice so that she’s less likely to need an exchange transfusion. This treatment remains the standard of care, most commonly using fluorescent white light. (Blue light is most effective for intensive phototherapy.) Phototherapy is the use of light to photoisomerize unconjugated bilirubin into forms that are more water-soluble and can be excreted rapidly by the liver and kidney without glucuronidation. It provides definitive treatment of neonatal hyperbilirubinemia and prevention of kernicterus.
  9. This treatment remains the standard of care, most commonly using fluorescent white light. (Blue light is most effective for intensive phototherapy.) Phototherapy is the use of light to photoisomerize unconjugated bilirubin into forms that are more water-soluble and can be excreted rapidly by the liver and kidney without glucuronidation. It provides definitive treatment of neonatal hyperbilirubinemia and prevention of kernicterus.
  10. Phototherapy The infant is placed under artificial light in a warm, enclosed bed to maintain a constant temperature. The baby will wear only a diaper and special eye shades to protect the eyes. If the bilirubin level is not too high or is not rising quickly, you can do phototherapy at home with a fiberoptic blanket, which has tiny bright lights in it. You may also use a bed that shines light up from the mattress. The nurse will return daily to check your child's weight, feedings, skin, and bilirubin levels. Kernicterus: Neurological syndrome resulting from neurotoxic affects of unconjugated bilirubin on basal ganglia and brainstem nuclei Phase 1: Poor suck, hypotonia and lethargy
  11. Intravenous immunoglobulin (also called IVIg). If you and your baby have different blood types, your baby may get immunoglobulin (a blood protein) through a needle into a vein. This can help her treat her jaundice so that she’s less likely to need an exchange transfusion.
  12. Rh factor is a protein that may be found on the surface of red blood cells. If you carry this protein, your blood is Rh POSITIVE. If you don't carry this protein, your blood is Rh negative. Sometimes a mother with Rh-negative blood is pregnant with a baby that has Rh-POSITIVE blood. This can cause a problem if the baby's blood enters the mother's blood flow. The Rh-positive blood from the baby will make the mother's body create antibodies. This is called isoimmunization. The antibodies will attack any Rh-positive blood cells. This will not cause a problem for the mother. However, the antibodies can pass to the developing baby and destroy some of the baby's blood cells See more at: http://medicine.med.nyu.edu/conditions-we-treat/conditions/rh-incompatibility-and-isoimmunization#sthash.mvkEPRuj.dpuf When people who have one blood type receive blood from someone with a different blood type, it may cause their immune system to react An ABO incompatibility reaction can occur if you are given the wrong type of blood during a blood transfusion. It is a rare, but serious and potentially fatal, response by your immune system to incompatible blood BO incompatibility is a common and generally mild type of haemolytic disease in babies. The term haemolytic disease means that red blood cells are broken down more quickly than usual which can cause jaundice, anaemia and in very severe cases can cause death. During pregnancy, this breakdown of red blood cells in the baby may occur if the mother and baby’s blood types are incompatible and if these different blood types come into direct contact with each other and antibodies are formed. Gilbert's syndrome is a common, mild liver condition in which the liver doesn't properly process a substance called bilirubin. Bilirubin is produced by the breakdown of red blood cells. Gilbert's (zheel-BAYRZ) syndrome typically is harmless and doesn't require treatment. Gilbert's syndrome is caused by an inherited gene mutation Crigler-Najjar syndrome is a severe condition characterized by high levels of a toxic substance called bilirubin in the blood (hyperbilirubinemia). Bilirubin is produced when red blood cells are broken down. This substance is removed from the body only after it undergoes a chemical reaction in the liver, which converts the toxic form of bilirubin (called unconjugated bilirubin) to a nontoxic form called conjugated bilirubin. People with Crigler-Najjar syndrome have a buildup of unconjugated bilirubin in their blood (unconjugated hyperbilirubinemia)