Figure 1. Total bilirubin vs hours of life Case Presentation HPI: F.A. is a 5 month old female born term by SVD with vacuum assist with no other complications, who was discharged at 24 hours of life with a bilirubin of 6.7. She presented to the ED with gross developmental delay and increased fussiness. PMH was remarkable for hyperbilirubinemia noted on day of life three. She had a marked decrease in PO intake and voids, and was noted by parents to be inconsolable and irritable (Figure 1). She required a seven day hospitalization with intensive phototherapy and rehydration. Max T bili at that time was After phototherapy and rehydration, she symptomatically improved and was discharged home. She initially passed hearing test in newborn nursery, but failed repeat hearing test prior to discharge. General fussiness has been noted since birth but worsening over the last week and she continues with episodes of inconsolability, crying for most awake hours. Parents have noted upper body stiffness but with floppy neck muscles. At five months she does not lift her head, does not babble, cannot sit, but is able to recognize her parents, and has a social smile since 2-4 weeks of age. Vaccinations were up to date. Family immigrated from Iraq but patient was born in Texas. Physical Exam Patient is afebrile, intermittently fussy but non-ill appearing. Her weight is 8.15 kg (85th percentile), height is 64 cm (32 nd percentile), and head circumference is 40.5 cm (15 th percentile). HEENT exam reveals ability to focus, no visual tracking, and occasional unconjugate gaze. She also has difficulty with upward gaze. The tongue demonstrates choreoathetoid movements. She has poor head control, significant head lag, and moderate head control in the upright position. She is unable to lift her head from the prone position. Rigidity is noted of the upper and lower extremities but she is overall hypotonic. F. A. was admitted in stable condition. Workup for potential causes of her developmental delay and fussiness included obtaining basic electrolytes, CBC, and bilirubin levels which were unrevealing. Clinically she was well appearing though with intermittent fussiness, and nothing suggested sepsis or other overwhelming infection. Given her history, however, there was concern that our patient’s constellation of developmental delay and fussiness were sequelae of hyperbilirubinemia. An MRI was obtained, which showed basal ganglia changes consistent with kernicterus. Workup for potential causes of kernicterus revealed G6PD deficiency. She was seen by physical, occupational, and speech therapists while admitted. Upon discharge she was referred to hematology and neurology. Referral for ECI evaluation and instructions to follow up with PCP were also given. A case of Kernicterus: A cautionary tale Carmelle Tsai, MD PGY-1, Athra Kaviani, MD PGY-1, and Zena Ghazala, MD PGY-1 C H I L D R E N ’ S M E D I C A L C E N T E R, D A L L A S Labs and Imaging Clinical Course Discussion References One of the most concerning aspects of F. A.’s history was the rapid rate of rise of her serum bilirubin between 24 and 72 hours of life. Though the etiology was not completely clear, in hindsight we were able to identify multiple risk factors for hyperbilirubinemia. Major risk factors according to AAP guidelines included hemolytic disease (G6PD, although unknown initially), and exclusive breastfeeding. Minor risk factors included serum bilirubin in the high intermediate risk zone, and maternal age > 25 years of age 1. Though unclear from initial birth documentation, we also noted that our patient had a vacuum delivery and “caput” on her birth discharge physical exam. It is possible our patient may have developed a cephalohematoma from the delivery, which would also have been a major risk factor. The combination of the aforementioned risk factors likely contributed to the rapid rate of rise. This case was also notable because both clinical and lab findings were classic for the diagnosis of kernicterus. In acute bilirubin encephalopathy, neonates in the early phase are sleepy, hypotonic, and have a high pitched cry. In the intermediate phase, they may be febrile, lethargic, have poor suck, irritable, difficult to console, and may demonstrate hypertonia with retrocollis or opisthotonos. In the advanced stage, patients develop apnea, inability to feed, seizures, coma, hypertonicity, and may continue on to respiratory failure or intractable seizures. Thankfully F. A. did not enter the advanced stage, but her mother’s chief complaints upon admission when her serum bilirubin was found to be 34.7, were that F. A. was lethargic, not eating well, irritable, and difficult to console. In kernicterus, the chronic sequelae of bilirubin induced neurologic dysfunction (BIND), patients have choreoathetoid cerebral palsy, sensory hearing loss, and gaze abnormalities (particularly limitation of upward gaze) 2. Our patient’s physical exam was consistent with this description, and notably, our patient failed a repeat hearing screen at the end of her first admission. Additionally, our patient’s MRI showed classic findings of kernicterus, with globus pallidus lesions 3. Interestingly enough, in the Pilot Kernicterus Registry of 61 cases of kernicterus, G6PD deficiency was one of the leading etiologies identified 4. This case highlights the importance of close follow-up in newborns with hyperbilirubinemia. In F. A.’s case, her G6PD deficiency was unknown at birth but likely played a significant role in how quickly her serum bilirubin rose to toxic levels. This case is a sobering reminder to practitioners that we may not always know all of the risk factors that could lead to such significant hyperbilirubinemia, and when in doubt, closer follow-up can be preventative. It also adds to data that some have used to suggest that screening for G6PD could significantly impact the number of future cases of kernicterus, as it has been found to be a common etiology. Initial laboratory results reveal a total bilirubin of 0.50 mg/dL and direct bilirubin of 0.20 mg/dL. The results of serum electrolytes, liver enzyme studies, and complete blood count with differential are within the reference range for age. Her total CK is 214 units/L, lactate is 1.6 mmol/L, and pyruvate mmol/L. DAT is negative. Quantitative G6PD is 4.7 units/g Hgb (nl range ). Blood and urine cultures are negative. Brain MRI reveals symmetrical hyperintense lesions of the globus pallidus on T2 weighted imaging (Figure 2). Figure 2. MRI brain without contrast, T2 weighted imaging 1. Subcommittee on Hyperbilirubinemia. Management of Hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. Vol. 114 No. 1 July 1, 2004 pp Y Frank and S Ashwal. Neurologic Disorders Associated with Gastrointestinal Diseases and Nutritional Deficiencies. Swaiman: Swaiman's Pediatric Neurology, 5th ed. Elsevier, U Parashari et al. Changes in the globus pallidus in chronic kernicterus. Journal of Pediatric Neuroscience. Vol. 4 No. 2 July-Dec 2009 pp L Johnson, V Bhutani, A Brown. System-based approach to management of neonatal jaundice and prevention of kernicterus. The Journal of Pediatrics. Vol. 140 No. 4 April 2002 pp Many thanks to Dr. Katherine Rodgers, our attending physician.