August 2007
 “My baby is not right and she’s got
yellow eyes”
 5 week old Caucasian female who presents
with lethargy, jaundice and poor weight
gain.
 PCP referred to a gastroenterologist for
rising direct hyperbilirubinemia
 Birth history:
 FT C/S for failure to progress
 BW 3.61 kg
 NICU for 6 days b/c of hypothermia and hypoglycemia 
sepsis w/u done was negative
 NICU labs:
 initial glucose 27
 bili t/d (6dol) 15.3/1
 Diet: Breastfed until DOL 8 when changed to hydrolyzed
protein formula secondary to persistent elevated bili.
Feeding well per mom
 Elimination: 10 wet diapers/day, 2 yellow-brown seedy
stools/day
 Patient was seen by PCP for jaundice at 5 weeks.
 She was noted to have a bili t/d of 9.5/4.5
 Patient was referred to a gastroenterologist for further
workup
 What is direct hyperbilirubinemia exactly?
 Direct bilirubin >2 mg/dL
 Direct bilirubin > 20% of total bili
 Direct hyperbilirubinemia effects 1 in
2500 infants.
 That’s fairly common!
 BUT…it’s never normal!
Don’t be afraid to ask…
 Wt 3.55 kg (10-25%) Lt 55 cm (75%) HC 39 cm (50%)
 T 98.7 P 160 R 36 B/P 92/58
 Gen: quiet, responds to mom, no apparent distress,
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minimal subcutaneous fat, no dysmorphic features
HEENT: mm dry, sclera icteric, OP clear
CV/RESP: RRR no murmurs, CTAB
Abd: soft, ND, no HSM, no masses
GU: normal female
Skin: capillary hemangioma in right axilla
Neuro: grossly intact, + moro, +suck, +grasp
Top 3 diagnoses
Top 3 tests
…with rationale por favor
 Elevated LFTs
 Hepatocellular injury
 Elevated Alk phos and GGT-- point to obstructive
conditions
 Make sure to fractionate the bili!
 TORCH titers, Ucx, Sweat test, Urine reducing
substances if indicated by Hx/PE
 Follow up on NBS!
 Consider liver function studies as well.
 139 106 13
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101
4.6 18 0.7 10.3
Alb 2.3
Bili t/d 8.9/4.2
AST 50/ALT 22/ AP 385
ESR 8 (0-20)
 NBS- normal from the
state lab
 14.6
11 537
33
s 14 l 81 m3
 Ammonia 58 (29-70)
 α 1 antitrypsin - normal
 UA- 1.004 pH 5; 1 WBC;
0 RBC; no RS
 Cultures sent BCx, UCx,
CSF Cx
 IVF
 IV Antibiotics
 Breastfeed or formula ad lib
 Is and Os monitored
 Scans ordered
 Abdominal u/s
 Reason for order: Exclude surgical cause of extrahepatic
biliary obstruction
 Result: NORMAL
 Hepatobiliary nuclear scan
 Reason for order: Look for patency of biliary tract R/O
biliary atresia
 Result: NORMAL, gallbladder visualized and excretion
was normal
 The astute T3, just joking it’s a L3, questions the UOP
on rounds. She noticed that it was 6 cc/kg/hr.
 The resident had failed to check the baby’s Is & Os for
the day. Whoops.
As a group, refine your problem definition and
differential
Do we need any other labs/ tests? Why?
 Intrahepatic Cholestasis
 Primary
 Alagille Syndrome
 Idiopathic Neonatal
Hepatitis
 Acquired
 Drugs/ Fetal Alcohol
 Sepsis
 TORCH
 Hep B
 HIV
 TPN
 Endocrine Disorders
 Hypothyroidism
 Hypopituitarism
 Extrahepatic Cholestasis
 Biliary Atresia
 Choledochal cyst
 Choledocholithiasis cyst
 Genetic/ Metabolic
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α 1 antitrypsin
Cystic fibrosis
Galactosemia/ Fructosemia
Gaucher disease
Niemann Pick
Glycogen storage disease
Trisomy 18
Trisomy 21
Tyrosinemia
Alagille
Syndrome
AD genetic d/o
with paucity of
bile ducts. May
also have PPS
and vertebral
defects
Features:
•Long nose with
bulbous tip
•Triangular face
•Broad forehead
 Most common and
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serious cause of direct
hyperbilirubinemia
Destroys the intra- and
extrahepatic biliary tree
May also see acholic
stools
Should be diagnosed
before 2 months--- HIDA
Tx: Kasai then transplant
 Idiopathic neonatal
hepatitis
 Self limited- resolves in
3-4 weeks
 Giant cells are seen on
biopsy
 Alpha 1 Antitrypsin
 Most common genetic
cause of acute and
chronic liver disease in
children
 Liver retains abnormally
folded protein
 May also develop lung
disease (later in life)
 Coagulopathy
 Fat malabsorption
 Ascites
 Encephalopathy
 What do we think about UOP of 6 cc/kg/hr?
 What could be the cause?
 Looking back at labs done during the
hospitalization, it was noted that the serum sodium
peaked at 149 mEq/L
 What are we worried about now?
 “Flavorless Urine”
 Characterized by:
 Inability to concentrate urine
 Polyuria
 Polydipsia
 Cause
 ADH deficiency- Central
 Lack of end organ response to ADH- Nephrogenic
 Thick limb of ascending loop of Henle
 Collecting duct
 Characteristics in infancy
 FTT
 Vomiting
 Constipation
 Unexplained fevers
 Shock (hypovolemic)
 Convulsions
 Urine Osmolality= 167 mOsml/L (>200)
 Serum Osmolality= 300 mOsml/L (275-295)
 DDAVP was given  UOsm of 310 mOsml/L
 What type of Diabetes Insipidus is this?
 CENTRAL
 The kidney responded appropriately to DDAVP dose.
DI
SIADH
 High serum Na
 Low serum Na
 Low urine SG <1005
 Low serum Cl
 Low urine osm 50-200
 Inappropriately
 Low vasopressin
concentrated urine
 Euvolemic or
hypervolemic
 Tx: Fluid restrict
 Tx: DDAVP
Why does this girl have central DI?
What tests do we want now?
 MRI was done- Pituitary was completely normal!
 In Central DI- the signal on T1 is usually abnormal
(not as bright (hyperintense) as usual)
 Further investigation of the pituitary was done. Why?
 Central DI
 The glucose in the NICU was low
 ? Cortisol deficiency
 ? Growth hormone deficiency
 Result: Serum cortisol  low for age
 The resident went back to spend some time examining
and observing the infant.
 She noted that the eyes seemed to “wander”. That is,
the baby could not fix her gaze
 Why? What should you do at this point?
 Ophthalmology consult
was obtained
 Impression:
Bilateral optic nerve hypoplasia
 So what do we have now?
 Direct hyperbilirubinemia
 Central Diabetes Insipidus
 Cortisol deficiency
 Optic Nerve Hypoplasia
 Can we tie all these problems into one diagnosis?
Septo-Optic Dysplasia
(SOD)
 One of the most common forms of congenital growth
hormone deficiency
 Results from incomplete development of forebrain &
pituitary
 Must have 2 of these 3 features for a diagnosis
 Optic nerve hypoplasia
 Absent septum pellucidum/corpus callosum
 Pituitary endocrinopathy (deficiency)
 Isolated GH deficiency
 Multiple pituitary hormone deficiencies
 May also see other midline defects (ex cleft lip)
 MRI results widely vary
 Varying degrees of endocrine
disturbance seen
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None
GH
TSH
LH/FSH
ACTH
Prolactin
ADH
 Did you know??
 Hypopituitarism can
lead to cholestasis
 Short stature
 Precocious/ Delayed Puberty
 Diabetes Insipidus (25%)
 Most cases are sporadic but familial forms do
occur suggesting genetic defects may play an
important role
 Viruses
 Teratogens
 Continued to have low cortisol (replaced)
 Became hypothyroid and was started on thyroxine
 Direct hyperbilirubinemia resolved with DDAVP
What are your take away points?
Hope you enjoyed the puzzler and learned something new!