Transcript C-38_Kinra - Advocate Health Care

Case Report on Neonatal Iron Storage
Disease
Anushka Kinra, DO, Leanne Mihata, MD, Ali Ghazi-Askar MS, MD
Department of Pediatrics, Advocate Hope Children’s Hospital
Introduction:
Hypoglycemia is a common finding in the newborn period of life.
However, when co-existing with coagulopathy, direct
hyperbilirubinemia, and clinical jaundice, it should alert one to
consider liver failure. In this case report, we describe a patient with
neonatal iron storage disease, which is a rare disease that remains one
of the most common causes of liver failure in the neonate. If left
untreated this disease is fatal in the first few weeks of life and may
require a liver transplant (Leonis, et al).
Methods:
Literature search conducted via PubMed included search terms
“liver failure AND neonatal,” “hepatobiliary disease AND
neonatal,” “neonatal hemochromatosis,” “iron metabolism,”
“management of neonatal hemochromatosis” our search was
limited to English language text only.
Differential diagnosis of Neonatal
liver failure:
The differential diagnosis of liver failure in a neonate is
complex and should include anatomic, metabolic, endocrine
and infectious etiologies (Saenz, MS et al).
Anatomic
-Biliary atresia
-Choledochol cyst
-Alagille Syndrome
Metabolic
-Galactosemia
-Tyrosinemia
-Crigler-Najjar
-Neonatal Iron Storage Disease
Endocrine
-Hypothryoidism
-Hypopituitarism
Infectious
-Parvovirus B19
-Epstein-Barr Virus
-Cytomegalovirus
Case Presentation:
Etiology:
A one-hour-old female infant is admitted to the neonatal intensive
care unit after routine bedside glucose testing revealed a blood
glucose of 11. After hypoglycemia was confirmed with a venous
sample, intravenous access was immediately obtained and the baby
was given a bolus of D10W. The baby was born to a 32 year old
G2P2001 woman at 38 weeks plus 2 days gestation via cesarean
section secondary to decreased fetal movement. A biophysical
profile done on day of delivery was 4/10, and oligohydramnios had
also complicated the pregnancy. APGAR scores were 7 and 9 at 1
and 5 minutes. The baby transitioned well and was initially taken
to the newborn nursery while the mother recovered from surgery.
Maternal prenatal labs were available and revealed maternal blood
type of A positive, GBS positive screen, but as baby delivered via
cesarean section prior to onset of labor, intrapartum antibiotics
were not indicated. Maternal serologies for HIV, Hep B, and HSV
were negative; VDRL was negative and she was rubella immune.
Upon admission to the neonatal intensive care unit, the baby
was noted to have poor color, decreased activity, slightly icteric
sclera, a II/VI soft, systolic heart murmur, splenomegaly and
decreased tone with normal reflexes. There were no dysmorphic
features noted. She had mild respiratory distress, thus, was placed
on a nasal cannula at 2 liters per minute with good response. A
complete blood count and blood culture were obtained for sepsis
evaluation following placement of umbilical venous and arterial
catheters. Empiric antibiotics were started with ampicillin and
gentamicin. The WBC count was 6.7x103/µL (6.7x109/L),
differential 76% neutrophils, 1 band, 11% lymphocytes and 6%
monocytes, Hgb was 17.4 g/dL (17.4 g/L), Hct was 48% (0.48),
and platelet count was 29x103/µL (29x109/L), with a repeat platelet
count of 15x103/µL (15x109/L). A DIC panel was done which
revealed a prothrombin time of 36 seconds, activated partial
thromboplastin time of 57 seconds, fibrinogen of 43 mg/dL (normal
203-424 mg/dL) and quantitative d-Dimer of 10.58 mg/L. She had
minimal oozing of blood from her umbilical arterial line; head
ultrasound showed no intraventricular hemorrhage. She was
transfused platelets and fresh frozen plasma and serial DIC panels
were done every 8 hours. Total bilirubin done at 12 hours of life
was elevated at 12.2 mg/dL. Triple phototherapy was started and
serial bilirubin measurements obtained. A repeat bilirubin panel
done at 18 hours of life showed total bilirubin of 12.4 mg/dL and
direct bilirubin of 6.5 mg/dL. The baby was noted to have a heart
rate between 86-121 beats per minute on the second hospital day;
echocardiogram showed normal function, hypertrophy of the
intraventricular septum with no outflow tract obstruction and a
small patent foramen ovale. Electrocardiogram was normal.
Further evaluation revealed the following results: normal thyroid
studies; mild heterogeneity of echotexture of liver on ultrasound,
but otherwise normal study; negative hepatitis panel, negative work
up for CMV, toxoplasmosis, parvovirus, EBV, HHV 6, enterovirus
and acute HSV infection. Further studies led to the patient’s
diagnosis.
Etiology of NISD is not completely understood. However, the
prevailing theory proposes an alloimmune etiology where a mother
becomes sensitized to fetal antigen and may develop an IgG
antibody response to the antigen. For this to occur there must be an
exposure of the fetal liver antigen to maternal circulation and this
antigen must be recognized as “foreign.” (Whitington PF, Padmini)
This results in a humoral alloimmune (immunity gained from
individuals of the same species) response. When the maternal IgG
rises to a sufficient titer, they bind to the target antigen in the fetus
resulting in fetal dysregulation of iron metabolism and consequent
intrahepatic and extrahepatic iron deposition.
Case Discussion:
An example of iron deposition demonstrated in the liver and extra-hepatic sites
(spleen) on T2 weighted abdominal MRI image
Iron studies in this infant showed ferritin of 2643 ng/mL (range 8252), total iron of 177 mcg/dL (range 50-177), total iron binding
capacity of 186 mcg/dL (range 100-400) and iron saturation of 95%
(range 15-45). Serum ammonia level was 89 µmol/L (range 28-88),
and alpha fetoprotein level was 87,328 ng/mL (range 48,406 +/34,718 ng/mL). An abdominal magnetic resonance imaging study
revealed decreased signal intensity of the liver on T2-weighted
sequences and enlarged spleen measuring 8 centimeters without
altered signal intensity. On in-phase images, the liver intensity
decreased, which was suggestive of iron deposition. The pancreas
appeared normal. A buccal biopsy was done to evaluate for iron
deposition in the salivary glands, but no salivary glands were
visualized. The child was transferred to a liver transplant center
with the presumed diagnosis of neonatal iron storage disease
(NISD).
The Condition:
An example of a buccal biopsy demonstrating iron
deposition in salivary glandular tissue
Neonatal iron storage disease is a severe liver disease associated
with both hepatic and extrahepatic iron deposition, leading to
liver failure within the first few weeks of life. This disease was
formerly termed “Neonatal hemochomatosis.” However, since the
adult disease, Hemochromatosis has a complete different
pathophysiology, a nomenclature change has been made to more
accurately classify this as Neonatal iron storage disease. Patients
born with NISD are commonly born premature and exhibit
symptoms including hypoglycemia, coagulopathy, cholestatic
jaundice, and poor feeding. Additional findings include
splenomegaly and pancreatic islet cell hyperplasia leading to
glucose dysregulation.
Diagnosis:
The hallmark of NISD is extrahepatic siderosis with sparing of
the retiuloendothelial system confirmed by tissue biopsy or
MRI. (Knisely A.S. et al). Biopsy of the oral mucosa allows
for collection of glandular tissue where siderosis has occurred.
However, oral mucosal biopsies often fail because the
specimen is inadequate and do not contain submucosal glands
(Whitington PF).
Management:
Management of NISD includes iron chelation, supportive
therapy with anti-oxidants, post-natal exchange transfusion,
and liver transplantation (Escolano-Margarit, et al). Liver
transplantation is the only curative management for neonatal
iron storage disease.
Treatment of this patient included multiple blood product
transfusions to address her DIC and high glucose infusion rate
to compensate for her impaired glucose metabolism. Upon
transfer, patient received intensive therapy at a liver transplant
center with iron chelation and anti-oxidant therapy. However,
while awaiting liver transplant, she developed sepsis and
succumbed to her illness.
Conclusion:
There must be a high index of suspicion for NISD in any
neonate presenting with hypoglycemia, coagulopathy,
jaundice, cholestasis, and poor feeding. This allows for early
diagnosis and treatment. If a mother has given birth to a child
with NISD, early intervention and consultation with a
pediatric gastroenterologist, obstetrician, and pediatric
hematologist are essential for future pregnancies. Literature
has shown that after a child has been born with NISD, there is
a 75% chance or greater that each subsequent infant born to
that mother will be affected with NISD. Due to the high rate of
recurrence, counseling should be offered to mothers with
affected children who plan to become pregnant again so they
may start IVIG therapy by the 18th week of gestation
(Whitington, Hibbard). Finally, providing support and
counseling for a mother whose child has been diagnosed with
NISD is extremely important.
References:
Leonis MA, Balistreri WF. Neonatal hemochromatosis: it’s OK to say “no” to antioxidantchelator therapy. Liver Tranpl 2005;6:880-4
Saenz MS et al. Neonatal liver failure: a genetic and metabolic perspective. Current Opinion in
Pediatrics 2010, 22: 241-245
Whitington PF, Padmini M. Neonatal Hemochromatosis: Is it an alloimmune disease?
Pediatric;Gastroenterology and Nutrition 2005; 40: 544-9
J
Knisely A.S. et al. Neonatal hemochromatosis. Gastroenterol Clin N Am 32 (2003) 877-889
Whitington PF. Fetal and infantile hemochromatosis. Hepatology 2006; 43:654-660
Whitington, PF, Hibbard JU. High-dose immunoglobulin during pregnancy for recurrent
neonatal hemochromatosis. The Lancet. Vol 364 Iss 9446 1690-1698
Escolano-Margarit, MV et al. Exchange Transfusion as a Possible Therapy for Neonatal
Hemochromatosis. JPGN. Vol 50 Num 5 May 2010
Acknowledgements:
Dr. Nagpal, Dr. Alattar, Dr. McFall,
Dr. Jazmines, Dr. Collins, Dr. Ramilo, and Dr. Mehta