Cholestasis and Hepatic Iron Deposition in an Infant with Complex Glycerol Kinase Deficiency Diana Montoya-Williams, MD, Meredith Mowitz, MD, MS
Total Page：16
File Type：pdf, Size：1020Kb
Cholestasis and Hepatic Iron Deposition in an Infant With Complex Glycerol Kinase Deficiency Diana Montoya-Williams, MD, Meredith Mowitz, MD, MS We present a 6-week-old male infant with persistent hyperbilirubinemia, abstract hypertriglyceridemia, elevated creatine kinase levels, and transaminitis since the second week of life. When he developed hyperkalemia, clinical suspicion was raised for adrenal insufficiency despite hemodynamic stability. A full endocrine workup revealed nearly absent adrenocorticotropic hormone. Coupled with his persistent hypertriglyceridemia (peak of 811 mg/dL) and elevated creatine kinase levels (>20 000 U/L), his corticotropin level lead to a clinical diagnosis of complex glycerol kinase deficiency (GKD), also known as Xp21 deletion syndrome. This complex disorder encompasses the phenotype of Duchenne muscular dystrophy, GKD, and congenital adrenal hypoplasia due to the deletion of 3 contiguous genetic loci on the X chromosome. Division of Neonatology, Department of Pediatrics, Our case exemplifies the presentation of this disorder and highlights the University of Florida, Gainesville, Florida important lesson of distinguishing between adrenal hypoplasia congenita and congenital adrenal hyperplasia, as well as the sometimes subtle Dr Montoya-Williams cared for the patient and drafted the initial manuscript; Dr Mowitz cared presentation of adrenal insufficiency. To our knowledge, it is also the first for the patient and reviewed and edited the reported case of complex GKD deficiency with the additional finding of manuscript; and both authors approved the fi nal hepatic iron deposition, which may indicate a potential area for exploration manuscript and agree to be accountable for all aspects of the work. regarding the pathogenesis of liver injury and cholestasis seen in cortisol- DOI: https:// doi. org/ 10. 1542/ peds. 2016- 1479 related endocrinopathies. Accepted for publication Dec 12, 2016 Address correspondence to Diana Montoya- Williams, MD, Department of Pediatrics, Division of Adrenal hypoplasia congenita (AHC) (DMD), which is then often labeled Neonatology, University of Florida, PO Box 100296, is a rare cause of congenital adrenal complex GKD or Chromosome Xp21 Gainesville, FL 32610. E-mail: dmontoyafontalvo@ insufficiency that often presents deletion syndrome due to the position peds.ufl .edu early in life, with salt wasting and of all 3 loci on the short arm of the X PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, hypoglycemia leading to growth chromosome.2 Isolated GKD can cause 1098-4275). failure and hemodynamic crises. 1 metabolic acidosis and hypoglycemia Copyright © 2017 by the American Academy of It may present similarly to the but is usually asymptomatic and Pediatrics more common congenital adrenal detected incidentally through FINANCIAL DISCLOSURE: The authors have hyperplasia, but has important hyperlipidemia testing, as it causes indicated they have no fi nancial relationships relevant to this article to disclose. clinical distinctions, such as the a pseudohypertriglyceridemia. 3 potential for hyperpigmentation, Complex GKD, however, carries a FUNDING: No external funding. cryptorchidism and other signs of much more serious prognosis, as it can POTENTIAL CONFLICT OF INTEREST: The authors hypogonadotropic hypogonadism, lead to life-threatening adrenal crises have indicated they have no potential confl icts of interest to disclose. and associated disorders. AHC can if unrecognized. be autosomal recessive or present as part of a contiguous X-linked To cite: Montoya-Williams D and Mowitz M. recessive genetic syndrome together PRESENTATION Cholestasis and Hepatic Iron Deposition in an with glycerol kinase deficiency (GKD) The case was a 3100-g 6-week- Infant With Complex Glycerol Kinase Defi ciency. Pediatrics. 2017;140(1):e20161479 and Duchenne muscular dystrophy old male infant transferred to our Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 140 , number 1 , July 2017 :e 20161479 CASE REPORT NICU for further evaluation of his aspartate aminotransferase and and mild hypotonia, but notably no persistent hyperbilirubinemia, alanine aminotransferase showing hepatomegaly. He also had extremely hypertriglyceridemia, elevated a persistent fivefold elevation dark skin, which the parents reported creatine kinase (CK) levels, and despite discontinuation of parenteral was not present at birth but had transaminitis. He was born at 40 nutrition. He was further noted to developed quickly after birth. The weeks’ gestation by spontaneous have elevated triglyceride levels up remainder of the examination vaginal delivery to a 30-year-old to maximum of 811 mg/dL despite was normal. Laboratories in the gravida 1 para 0 mother who was being fed several different types of first week of admission revealed Group B Streptococcus positive formula. normal electrolytes but continued but otherwise had unremarkable hypertriglyceridemia, cholestasis, Given the continued elevation in prenatal serologies. Apgar scores transaminitis, and CK elevations his bilirubin and transaminases, he were 9 and 9 at 1 and 5 minutes, ( Table 1). We investigated for inborn received an extensive gastrointestinal respectively, and birth weight errors of bile acid metabolism by workup, including normal was 2946 g. Mother received sending total and fractionated bile abdominal imaging (ultrasound adequate intrapartum antibiotic acid levels, as elevations of unusual and upper gastrointestinal series), prophylaxis but was diagnosed with bile acids have been associated with normal pancreatic enzyme and chorioamnionitis; thus, the patient severe cholestasis and subsequent ammonia levels, and negative received 48 hours of antibiotics at liver damage. 5, 6 Although our hepatitis serologies. A hepatobiliary birth. He was also noted to have mild patient’s total bile acid levels were iminodiacetic acid scan conducted at jaundice in the first few days of life elevated (>128 μmol/L), his profile 1 month of life revealed no excretion attributed to ABO incompatibility, indicated nonspecific cholestasis of tracer from the liver; thus, a liver although his hemoglobin levels given the predominance of primary biopsy was done, which revealed showed no evidence of hemolysis. bile acids. focal intracellular cholestasis On day of life 5, he became febrile, with giant cell transformation of Over the next 2 weeks, he remained lethargic, and more jaundiced. some hepatocytes and moderately hospitalized working on oral feeds. He developed severe refractory increased iron stores, but no Routine laboratories at 7 weeks of hypotension and respiratory steatosis, fibrosis, necrosis, age revealed hyponatremia (130 failure. Laboratory testing inflammation, or features of biliary mmol/L) and hyperkalemia (8.1 revealed a significant coagulopathy atresia. The hepatic siderosis mmol/L) with normal renal function (international normalized ratio 3.9), raised concerns for neonatal (creatinine 0.18 mg/dL) and good hyponatremia, and hyperkalemia hemochromatosis, a phenotype of urine output on full enteral feeds in the setting of significant oliguria. severe liver disease with extrahepatic and no medications. Although he He was also noted to have signs iron deposition that can result remained hemodynamically stable, of end-organ ischemia with an from various causes. 4 Our patient his ongoing lack of a unifying elevation in his troponins, creatinine, underwent a buccal biopsy to look diagnosis and these laboratory transaminases, and CK levels. He for iron staining and a brain MRI to findings led to an investigation was managed with broad-spectrum look for iron deposition, but these of his adrenal function. Both antibiotics for presumed sepsis, were both normal. He was evaluated his cortisol (2.0 μg/dL) and and with multiple vasopressors and for inborn errors of metabolism aldosterone (<3.0 ng/dL) levels were hydrocortisone for his refractory that can cause liver disease, such as abnormally low. Concurrent plasma hypotensive shock. He received galactosemia, tyrosinemia, or α-1 adrenocorticotropic hormone and intramuscular vitamin K and fresh- antitrypsin deficiency, and was found plasma renin activity levels were frozen plasma transfusions over to have borderline elevated levels of noted to be extremely elevated at several days until normalization of acylcarnitines known to be falsely 3192 pg/mL (normal 5–46 pg/mL) his international normalized ratio. elevated by parenteral nutrition. and 66 ng/mL per hour (normal Otherwise this workup was negative. Extensive infectious workup, for age <37 mg/mL per hour), including bacterial, viral, and fungal Given the persistent laboratory respectively. Combining this evidence studies, remained negative. He slowly abnormalities, transfer to our NICU of adrenal hypofunction with his improved and was weaned from the was requested. On admission, he elevated CK levels, complex GKD was ventilator and all blood pressure was clinically stable, but his weight suspected. The laboratory was asked support, including steroids. All was below the third percentile, to correct his triglyceride levels for laboratory values normalized with down from the 15th percentile serum glycerols, which revealed a the exception of his direct bilirubin, at birth. Examination revealed true triglyceride level within the CK levels, and transaminases, with cryptorchidism, scleral icterus, normal range. Furthermore, glycerol Downloaded from www.aappublications.org/news by guest on October 1, 2021 e2 MONTOYA-WILLIAMS and MOWITZ