A Healthy Toddler With Fever and Lethargy Neha A. Suri, MD,a Colleen W. Meehan, MD, MPH,a Anjna Melwani, MDb

A 21-month-old previously healthy girl presented to the emergency abstract department initially with fever, rhinorrhea, and poor oral intake. She was subsequently discharged from the hospital on amoxicillin for treatment of acute otitis media but presented hours later on the same day with continued poor oral intake, decreased urine output, and lethargy. The patient was afebrile on examination without a focal source of infection or evidence of meningismus, but she was lethargic and minimally responsive to pain and had reduced strength in the upper and lower extremities. Initial laboratory analysis revealed leukocytosis with a neutrophil predominance and bandemia, hyponatremia, mild hyperkalemia, , elevated transaminases, a mild metabolic acidosis, glucosuria, ketonuria, and hematuria. Follow-up tests, based on the history and results of the initial tests, were sent and led to a surprising diagnosis. bDivision of Hospital Medicine and aDepartment of Pediatrics, Children’s National Health System, Washington, District of Columbia

Drs Suri and Meehan contributed to the concept and CASE HISTORY WITH SUBSPECIALTY mucous membranes were moist. design of the case report and drafted the initial INPUT Bilateral tympanic membranes were manuscript; Dr Melwani assisted with the conception of the case presentation and reviewed Dr Suri, Pediatrics, Resident, normal. On neurologic examination, she and revised the manuscript; and all authors Moderator was minimally responsive to noxious approved the final manuscript as submitted. stimuli and was given a Glasgow Coma Permission to present and publish this patient’s case A 21-month-old girl initially presented Scale score of 9. There was no evidence was obtained from the patient’s family. to the emergency department (ED) of meningismus. The remainder of the DOI: https://doi.org/10.1542/peds.2018-0412 with 2 days of rhinorrhea, poor oral examination results were within Accepted for publication Sep 18, 2018 intake, and a fever of 38.5°C. She was normal limits. diagnosed with acute otitis media and Address correspondence to Anjna Melwani, MD, discharged from the hospital on Dr Agrawal, what are your initial Division of Hospital Medicine, Children’s National Health System, 111 Michigan Ave NW, Suite 4800, amoxicillin. She presented back to the thoughts about this patient’s Washington, DC 20010. E-mail: amelwani@ same ED later that day with continued differential diagnosis? What would be childrensnational.org poor oral intake, decreased urine your first steps in her diagnostic PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, output, and lethargy. Her parents evaluation and management? 1098-4275). denied cough, shortness of breath, Copyright © 2019 by the American Academy of emesis, diarrhea, rash, seizurelike Dr Agrawal, Pediatric Emergency Pediatrics activity, focal neurologic deficits, head Medicine FINANCIAL DISCLOSURE: The authors have indicated trauma, and ingestion. They stated that The red flag in this child’s current they have no financial relationships relevant to this the patient had eczema and 1 previous presentation is the markedly abnormal article to disclose. episode of bronchiolitis but was Glasgow Coma Scale score of 9. Hence, FUNDING: No external funding. otherwise healthy. Immunizations were my initial evaluation would be focused POTENTIAL CONFLICT OF INTEREST: The authors have up to date. on assessing why this child’s mental indicated they have no potential conflicts of interest On examination, she was afebrile with status is so depressed. The differential to disclose. a heart rate at the upper limit of normal diagnosis for depressed mental status (143 beats per minute). Her respiratory in this child includes central nervous To cite: Suri NA, Meehan CW, Melwani A. A Healthy rate was 36. She was noted to be pale system infection, central nervous Toddler With Fever and Lethargy. Pediatrics.2019; 143(5):e20180412 with sunken orbits; however, her system trauma and/or bleed, ingestion

Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 143, number 5, May 2019:e20180412 DIAGNOSTIC DILEMMAS (diphenhydramine, benzodiazepine, a head CT scan. The point-of-care diagnosis. In addition to DKA, other barbiturates, marijuana, opiate, or blood glucose was elevated at causes of hyperglycemia include anticholinergics), 221 mg/dL. The CBC count revealed medication and stress. disturbance (, acute leukocytosis with a neutrophil hyponatremia with cerebral edema, or predominance and bandemia Dr Suri acute hypernatremia with osmotic (Table 1). The CMP was significant for Given the concern for DKA, the demyelination syndrome), and hepatic hyponatremia, mild hyperkalemia, patient was initially started on encephalopathy. In addition, severe and elevated urea nitrogen, blood intravenous (IV) fluids and an insulin acidosis may lead to mental status glucose, and transaminases. The infusion, with improvement being changes. Severe acidosis in this child blood gas test revealed a mild seen in her hyperglycemia. She was may be secondary to dehydration with metabolic acidosis with respiratory subsequently transferred by air to secondary poor perfusion; impending compensation. The urinalysis was our tertiary-care facility for further shock; unmasking an inborn error of notable for glucosuria, trace ketones, workup and management. , with the catabolic state and large blood with 2 to 5 red blood On arrival to our tertiary-care being induced by her recent poor oral cells (RBCs) per high-power field facility’s ED, the insulin infusion was intake; a new-onset diabetes mellitus (HPF). The urine drug screen result discontinued given a low suspicion presenting in diabetic ketoacidosis was negative. The rapid influenza and for DKA based on initial laboratories. (DKA); an intraabdominal catastrophe respiratory syncytial virus test results The patient was continued on with associated necrotic bowel; were also negative. The head CT scan maintenance IV fluids. Her initial uremia; acute anemia; or ingestion. and CXR were unremarkable. In examination was still concerning for addition, blood and urine cultures altered mental status, although the As a result, I would order a blood gas were collected to evaluate for sepsis, fi patient started responding to painful test to assess for acidosis, a nger- and the patient received 1 dose of stimuli. A repeat CBC count, CMP, stick to rapidly assess for ceftriaxone. hypoglycemia, a complete blood cell urinalysis, and blood gas test were (CBC) count to assess for anemia, Dr Cogen, given the elevated obtained (Table 1). These repeat a urinalysis to assess for ketosis, glucose, glucosuria, ketonuria, and laboratories were notable for a urine toxicology screen to assess for mild acidosis, particularly in the , significantly ingested drugs of abuse leading to setting of a patient presenting with elevated transaminases (more than mental status changes, and altered mental status, should we be double from before), and large blood a comprehensive metabolic panel concerned for DKA? on urinalysis with 10 RBCs per HPF. (CMP) to assess for electrolyte All other previously noted laboratory derangements, uremia, or hepatic Dr Cogen, Pediatric Endocrinology abnormalities had improved from previous results. Additional dysfunction. I would also assess for Given the patient’s presentation, we laboratories included g-glutamyl hypoxemia using pulse oximetry must consider DKA. However, given transpeptidase, , , and order a chest radiograph (CXR) that her pH is not ,7.3 and her and partial to assess for pneumonia or serum is not ,15, she thromboplastin time, hemoglobin cardiomegaly. Given the markedly does not satisfy the biochemical A1C, ethanol level, and abnormal mental status, I would criteria for the diagnosis of DKA.1 fl acetaminophen level (Table 1), with initiate uid resuscitation and order Additionally, with a diagnosis of DKA, results all being within normal limits. a head computed tomography (CT) one would expect polyuria, not Salicylate level was also obtained and scan. I would also consider a lumbar oliguria (as seen with this patient), was within the therapeutic range. puncture to assess for meningitis unless the patient was severely and/or encephalitis despite the dehydrated or had impending renal Dr Kumar, what specific infectious current lack of fever and compromise. Moreover, even with etiologies are on your initial meningismus. mild metabolic acidosis, one would differential for this patient? In expect moderate-to-large ketones. addition to the workup already Dr Meehan, Pediatrics, Resident, Trace ketonuria, as seen in this completed, would you recommend Moderator patient, could be secondary to a lumbar puncture? Initial workup included a finger-stick starvation; however, the glucose is blood glucose test, a CBC count, generally not elevated in starvation Dr Kumar, Pediatric Infectious a CMP, a blood gas test, lactate, ketosis. If there is a concern for Disease a urinalysis, a urine drug screen, diabetes, a hemoglobin A1C should Given that this patient has elevated rapid influenza and respiratory immediately be performed because transaminases and altered mental syncytial virus tests, a CXR, and that will generally confirm the status, I am particularly worried

Downloaded from www.aappublications.org/news by guest on September 27, 2021 2 SURI et al TABLE 1 Laboratory Data Test Reference Time: 0 h Time: 6 ha WBC, K/mL 6.48–13.02 18.7 10.59 Hemoglobin, g/dL 10.2–12.7 14.6 12.2 Hematocrit, % 30.9–37.9 43.1 33.8 Platelets, K/mL 214–459 281 262 Differential, % Segmented neutrophils 13–42 76 81 Band neutrophils 0–1104 Lymphocytes 35–67 6 5 Monocytes 6–16 8 9 Sodium, mmol/L 133–143 129 133 Potassium, mmol/L 3.3–4.7 5.6 5.4 Chloride, mmol/L 97–107 100 100 Carbon dioxide, mmol/L 16–25 17 16 Urea nitrogen, mg/dL 4–17 28 20 , mg/dL 0.20–0.79 0.45 0.19 Glucose, mg/dL 54–117 154 94 POC glucose, mg/dL 57–117 221 103 Calcium, mg/dL 8.9–9.9 7.6 7.5 Total protein, g/dL 6.0–7.8 5.8 6.0 Albumin, g/dL 3.5–4.7 3.5 2.9 AST, IU/L 16–57 2172 4563 ALT, IU/L 24–59 399 957 , IU/L ,0.8 0.8 0.4 , IU/L 185–383 131 138 Lactate, mmol/L 1.0–3.3 1.46 1.11 Blood gas pH 7.35–7.45 7.343 7.406

PCO2, mm Hg 40.0–50.0 27.6 24.9 Bicarbonate, mmol/L 22.0–29.0 15 15.7 Urine Specific gravity ,1.030 1.019 1.019 Glucose, mg/dL Negative 50 Negative Protein, mg/dL Negative 100 2+ Ketones, mg/dL Negative 5 1+ Blood, mg/dL Negative Large 3+ WBC, HPF ,62–51 RBCs, HPF ,32–510 Nitrites Negative Negative Negative Leukocyte esterase Negative Negative Trace Prothrombin time, s 11.8–14.3 — 14.8 Prothrombin time, INR 0.87–1.13 — 1.18 PTT activated (aPTT), s 22.5–38.0 — 30.1 GGT, U/L 2–15 — 9 Amylase, U/L ,106 — 9 Lipase, U/L 147–199 — 46 Hemoglobin A1C, % 3.4–6.1 — 5.0 Ethanol, mg/dL ,3.0 — ,3.0 Acetaminophen, mg/mL 0–50 — ,2.0 Salicylate, mg/dL Negative — 3.0 aPTT, activated partial thromboplastin time; GGT, gamma-glutamyl transferase; INR, international normalized ratio; POC, point of care; PTT, partial thromboplastin time; WBC, white blood cell count; —, not applicable. a Repeat laboratory results obtained after the initiation of IV hydration with normal saline, an insulin infusion, and ceftriaxone. about viral encephalitis. Potential transaminases, viral is also concern for tick-borne illness, etiologies for viral encephalitis on the differential. Depending on the including Rocky Mountain spotted include herpes simplex virus, vaccination history and exposure fever and ehrlichiosis, which may be varicella zoster virus, enterovirus, history, I would consider testing for present without a corresponding adenovirus, cytomegalovirus, and hepatitis A virus, , rash. In general, when there is Epstein-Barr virus. Given that this and . In addition, the a history of fever and the examination patient has significantly elevated overall presentation raises some is notable for altered mental status,

Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 143, number 5, May 2019 3 encephalitis and/or meningitis is and the . Higher AST in this Shortly after arrival on the floor, the a significant concern, and a lumbar child suggests dysfunction of one of patient’s CK value returned at puncture is recommended. these organs or tissues. Thus, 360 000 U/L ( 25–177 a (CK) level is U/L). Dr Suri a useful test. An ammonia level and Dr Melwani, can you share your A lumbar puncture was initially a complete abdominal ultrasound thoughts about this patient’s considered. However, several hours with Doppler (to evaluate the differential diagnosis now? What is after arrival to the tertiary-care structure of the , portal system, the differential diagnosis for facility, the patient demonstrated kidneys, and pancreas) are also rhabdomyolysis in a toddler? increased alertness with ability to useful tests. respond to questions appropriately. Dr Meehan Dr Melwani, Pediatric Hospital Thus, meningitis and/or encephalitis Medicine was considered less likely, and Dr Agrawal, given these initial ’ a lumbar puncture was not laboratory results, is there anything The patient s presentation was performed. Given the elevated you would add to the differential evolving and did not adequately transaminases, gastroenterology was diagnosis? Are there additional match the illness script for a common consulted. laboratories you would send? disease. In general, the differential diagnosis for rhabdomyolysis is Dr Badalyan, what is your impression Dr Agrawal extensive and commonly caused by ’ fi of the patient s signi cantly elevated infection, trauma, prolonged muscle I am intrigued by the urinalysis, transaminases, and is there any activity (exercise or seizures), or which revealed large blood but only 2 further testing you would medications.3,4 We also considered recommend? to 5 RBCs per HPF. Large blood in the urine in the absence of significant motor neuron diseases (ie, spinal fl Dr Badalyan, Pediatric RBCs indicates that either RBCs are muscle atrophy), in ammatory Gastroenterology being broken down and releasing myopathies (ie, polymyositis or ), and neuropathies In a patient with altered mental hemoglobin, which is contributing to 5 hemoglobinuria, or there is (ie, Guillain-Barre syndrome). In status and elevated liver enzymes, it addition, we included metabolic is important to determine if liver myoglobinuria from muscle ’ myopathies and muscular dystrophies failure is present because it may breakdown. The patient s elevated transaminases are consistent with in our differential diagnosis. Although require a rapid referral to fi rhabdomyolysis, and perhaps her CK levels were signi cantly a transplant center. In this child, an elevated, expected CK levels for each essentially normal international profound weakness was the source of what the medical providers of the above diagnoses are variable normalized ratio and direct bilirubin and depend on many different factors. are reassuring. Elevated misperceived as mental status changes in this sick toddler. In general, the CK level correlates to transaminases are never used to the degree of muscle injury or 2 Therefore, I would recommend diagnose liver failure. damage irrespective of etiology.6 sending a CK level test in the ED to The differential for elevated alanine assess whether the large blood noted Dr Meehan aminotransferase (ALT) and/or in the urine is actually myoglobinuria. aspartate aminotransferase (AST) in Virus-induced rhabdomyolysis was a child with fever and altered mental Dr Meehan considered given that the patient status is broad and includes sepsis, An ammonia level test was sent, and initially presented with fever and toxic ingestion, and metabolic the result was normal (46 mmol/L; rhinorrhea. Dr Kumar, in your disorders. In an older child, I would reference range 29–54 mmol/L). An experience, can a viral infection lead also consider Wilson disease and abdominal ultrasound result was also to such a severe presentation of autoimmune hepatitis because they normal. In addition, a CK level test rhabdomyolysis, or would this be can present with fulminant hepatitis. was sent and was still pending at the atypical? In this child, it was peculiar that AST time of admission to the hospitalist was significantly more elevated service. A repeat examination was Dr Kumar compared with the ALT (AST/ALT notable for improved mental status, Viral infections can cause severe ratio = 4.77). Although ALT is more although the patient had poor rhabdomyolysis, up to 1000 times the liver specific, high amounts of AST movement of extremities in response upper limit of normal, but this is can be found outside of the liver, to nailbed pressure with 2+ strength rare.7,8 Although influenza and other including in skeletal or cardiac in the lower extremities and 3+ viruses have been known to cause muscle, RBCs, the kidney, the brain, strength in the upper extremities. significant elevations in CK levels,

Downloaded from www.aappublications.org/news by guest on September 27, 2021 4 SURI et al they do not typically cause such level, an appropriate amount of acidosis The ECG should be read marked elevations on their own.7,8 for presentation, and the patient’s systematically. I recommend However, marked elevations may be normal growth and development thus examining the heart rate, rhythm, and seen in children with an underlying far. A long-chain fatty acid oxidation axis first and then looking for any genetic disorder predisposing them to defect is plausible, although there is no cardiac chamber enlargement, muscle breakdown. history of hypoglycemia, and the particularly left ventricular patient’s newborn metabolic screen hypertrophy (LVH) or right Dr Suri result was normal. ventricular hypertrophy. Given that the patient had no Regarding further tests, I recommend This patient’s history and age was fi identi able triggers and her CK level sending an acylcarnitine profile and concerning for possible Pompe was thought to be too high to be tests for serum amino acids and urine disease. On ECG, Pompe disease is secondary to a viral illness alone, the organic acids to evaluate for inborn characterized by a short PR interval genetics and metabolism team was errors of metabolism. I would also (,0.12 seconds) and extreme voltages consulted to evaluate for possible order an electrocardiogram (ECG) and (LVH).11 The ECG for this patient inheritable myopathies. consider an echocardiogram to look for qualified for borderline amplitudes of Dr Chapman, are you worried that evidence of Pompe disease and the R waves in the precordial leads this patient might have an inheritable cardiomyopathy, respectively. Finally, I concerning for possible LVH. However, myopathy? If so, which diseases are recommend sending a personalized LVH is less likely because of the fi you most worried about and why? gene panel to identify mutations in insigni cant S wave in precordial lead LPIN1 PYGM CPT2 PGK1 What further testing, if any, would , , ,and . V1 and the lack of Q waves in the you recommend? Mutations in these genes are associated inferior precordial leads. In addition, with lipin-1 deficiency, McArdle this patient’sPRintervalisnormal Dr Chapman, Pediatric Genetics and disease, carnitine palmitoyltransferase (between 0.12–0.2 seconds), and on Metabolism II deficiency, and phosphoglycerate both the ECG and CXR, there were no kinase deficiency, respectively. other signs of cardiac chamber Yes, I am concerned that this patient enlargement, making Pompe disease might have an inheritable myopathy. Dr Suri unlikely. The differential diagnosis includes A CXR and an ECG were performed, long-chain fatty acid oxidation and cardiology was consulted to Dr Meehan defects, glycogen storage diseases evaluate for cardiomyopathy. Dr fi (particularly Pompe disease), An acylcarnitine pro le and tests for Tague and Dr Sherwin, is the CXR or muscular dystrophy or congenital serum amino acids and urine organic ECG suggestive of cardiomegaly? myopathies, mitochondrial disorders, acids were sent and returned within lipin-1 deficiency, and exercise- normal limits. A personalized gene Drs Tague and Sherwin, Pediatric fi induced rhabdomyolyses, such as Cardiology panel to look for speci cgene LPIN1 PYGM CPT2 McArdle disease, carnitine mutations in , , ,and On CXR, cardiomyopathies can be PGK1 palmitoyltransferase deficiency, and was also sent and, after detected by measuring the diameter phosphoglycerate kinase deficiency.9 discharge from the hospital, returned of the cardiac silhouette compared Given the age of presentation, degree of with positive results for with that of the thoracic cavity. Also, CK elevation, association with a viral a heterozygous splice-site substitution examining the cardiac position and LPIN1 illness, and potassium abnormalities at in the gene. Interestingly, contours is helpful to estimate if LPIN1 presentation, lipin-1 deficiency is mutations in the gene that cardiac chambers are enlarged. It is fi favored over exercise-induced result in lipin-1 de ciency are also important to look closely at the rhabdomyolyses. Muscular dystrophy associated with recurrent episodes of lung fields for any evidence of venous and congenital myopathies are less rhabdomyolysis in childhood. congestion or pleural effusions, which likely in this patient given the absence of could suggest heart failure.10 a previous history of weakness. Pompe FINAL DIAGNOSIS AND DISCUSSION: disease is also less likely given that the The CXR for this patient was taken on AUTOSOMAL RECESSIVE ACUTE patient was previously healthy with no expiration, with only 7 ribs showing RECURRENT MYOGLOBINURIA FROM history of previous weakness, above the diaphragm, which can LIPIN-1 DEFICIENCY respiratory distress, or known falsely make the heart appear cardiomegaly; the CK value is also enlarged. However, the cardiac Drs Chapman and Mistry, Pediatric elevated for Pompe disease. A position and lung fields were grossly Nephrology mitochondrial disorder is also lower on normal. Therefore, the CXR has no This patient’s presentation is typical the differential given a normal lactate evidence of cardiomegaly. for autosomal recessive acute

Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 143, number 5, May 2019 5 recurrent myoglobinuria. Typically, rhabdomyolysis. The newborn Tamm-Horsfall protein and these patients present with recurrent metabolic screen does not test for precipitates in the tubules, causing episodes of severe rhabdomyolysis many of the metabolic myopathies, obstruction and acute tubular characterized by severe muscle including lipin-1 deficiency. necrosis.17 Therefore, the mainstay of weakness and mental status changes Therefore, a clinician must have therapy to prevent and treat kidney secondary to dehydration and a high suspicion for lipin-1 deficiency injury is to aggressively hydrate the electrolyte abnormalities. Laboratories to ensure appropriate diagnosis. If the patient with a goal to achieve a brisk are notable for significantly elevated history or physical examination of flow of urine and alkalinization to CK levels, elevated transaminases, and a child is notable for pain or weakness, prevent precipitation. hematuria. In addition, common a cardiac arrhythmia, concerning Typically, aggressive hydration is electrolyte disturbances include family history, or sudden death of initiated with normal saline or lactated hyperkalemia, hyponatremia, and a sibling, a CK level is recommended. Ringer solution with the goal of metabolic acidosis. Hyponatremia is Regardless of presenting symptoms or maintaining a urine output of 200 to thought to be secondary to the examination findings, a CK level test 300 mL per hour.6 Alkalinization is influx of extracellular fluid into the should also be sent if initial laboratories achieved with a concurrent use of IV injured muscles. This patient was also are notable for elevated transaminases sodium bicarbonate to achieve a urine noted to have hyperglycemia (likely or hematuria. A CK level .100 000 in pH .6.0.6 If the patient remains stress related) as well as leukocytosis a previously healthy young child should oliguric or anuric despite aggressive (likely due to a combination of prompt practitioners to consider hydration, or if the patient continues to inflammation and proinflammatory ordering molecular genetic tests for have severe electrolyte abnormalities, cytokines as well as metabolic myopathies. Of note, the hemodialysis is then used. In the hemoconcentration). common screening test results for setting of severe rhabdomyolysis, CK inborn errors of metabolism (pyruvate, levels should be monitored every 4 to Epidemiology and Clinical Features lactate, ammonia, acylcarnitine profile, 6hours,andIVfluids should be Lipin-1 deficiency is an increasingly serum amino acids, and urine organic continued until CK levels decrease to recognized cause of recurrent acids) are usually normal in patients #1000.6 In addition, patients with rhabdomyolysis in childhood. However, with lipin-1 deficiency. lipin-1 deficiency should receive high- the disease is rare, with ∼40 cases concentration glucose solutions at the being reported in the literature to date. Clinical Management onset of rhabdomyolysis.18 Children with this disease typically The mainstays of treatment during present between 15 months and acute episodes of rhabdomyolysis are 7 years of age with episodes of severe Precautions to (1) manage the underlying cause of rhabdomyolysis and significantly Parents of children with lipin-1 rhabdomyolysis and halt or elevated CK levels.9,12 These episodes deficiency should be provided with ameliorate the process, (2) provide are typically triggered by fever or mild a letter outlining emergency supportive care with aggressive illness, exercise, fasting, anesthesia, or treatment to ensure that any hydration, and (3) closely monitor medications.13 Almost all of the lipin-1 symptoms of weakness or pain in the and correct electrolyte, metabolic, deficiency cases in the literature have setting of illness are worked up and acid and/or base abnormalities. presented acutely.9,12–14 These patients rapidly with a high level of suspicion Correction of hyperkalemia is are at risk for rapid decompensation for rhabdomyolysis.13 In addition, especially critical because acute and cardiac arrest from arrhythmias patients with lipin-1 deficiency hyperkalemia can result in cardiac secondary to hyperkalemia that may should avoid medications that are arrhythmia and ultimately cardiac not be apparent on initial presentation. known to be associated with arrest. In fact, sudden death from arrhythmias rhabdomyolysis, such as and due to hyperkalemia is not uncommon The level of CK elevation in certain anesthetics.14 For example, in lipin-1 deficiency. Between acute rhabdomyolysis correlates with the inhaled anesthetics and episodes, affected children have normal severity of succinylcholine should be avoided strength and exercise capacity, although breakdown or injury. The higher the because of their potential to result in they are more susceptible to exercise- CK level, the higher the plasma muscle breakdown.14 In addition, before induced myalgias.14 is expected to be and the any major procedure or anesthesia, higher the risk of acute kidney dextrose-containing fluids should be Diagnosis injury.15 Rhabdomyolysis-associated administered to prehydrate and block Lipin-1 deficiency is, unfortunately, acute kidney injury is associated with catabolism.18 During these procedures, often not diagnosed until after higher mortality.15,16 When urine is CK levels should be monitored pre- and a patient presents with severe acidic, the myoglobin complexes the intraoperatively as well.

Downloaded from www.aappublications.org/news by guest on September 27, 2021 6 SURI et al ketoacidosis in children and adolescents. Pediatrics. 2004;113(2). Available at: www.pediatrics.org/cgi/ content/full/113/2/e133

2. Squires RH Jr, Shneider BL, Bucuvalas J, et al. in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr. 2006;148(5): 652–658

3. Elsayed EF, Reilly RF. Rhabdomyolysis: a review, with emphasis on the pediatric population. Pediatr Nephrol. 2010;25(1):7–18 4. Mannix R, Tan ML, Wright R, Baskin M. Acute pediatric rhabdomyolysis: causes FIGURE 1 and rates of renal failure. Pediatrics. Patient’s CK level trended over time. 2006;118(5):2119–2125 5. Teoh HL, Carey K, Sampaio H, Mowat D, Follow-up Sherwin, MD; and Lauren Tague, MD, Roscioli T, Farrar M. Inherited The patient was treated with for their numerous contributions to paediatric motor neuron disorders: aggressive hydration and bicarbonate, this article. We extend a special thank beyond spinal muscular atrophy. Neural Plast. 2017;2017:6509493 and her CK level appropriately you to pediatric genetics fellow decreased during her hospitalization Charles Billington, MD, for his efforts 6. Luck RP, Verbin S. Rhabdomyolysis: (Fig 1). In retrospect, it is likely that in helping us communicate with the a review of clinical presentation, ’ the initiation of the insulin infusion patient s family. etiology, diagnosis, and management. – may have prevented significant Pediatr Emerg Care. 2008;24(4):262 268 hyperkalemia and cardiac arrest by causing potassium to shift ABBREVIATIONS 7. Singh U, Scheld WM. Infectious intracellularly. After hospitalization, ALT: alanine aminotransferase etiologies of rhabdomyolysis: three initial sequencing of the 4 tested AST: aspartate aminotransferase case reports and review. Clin Infect Dis. 1996;22(4):642–649 genes revealed a heterozygous CBC: complete blood cell change in LPIN1, which is typically CK: creatine kinase 8. Agyeman P, Duppenthaler A, Heininger not associated with disease.13 CMP: comprehensive U, Aebi C. Influenza-associated myositis However, further testing later metabolic panel in children. Infection. 2004;32(4): – revealed a second mutation, CT: computed tomography 199 203 confirming the diagnosis of lipin-1 CXR: chest radiograph 9. Chan EK, Kornberg AJ, Ryan MM. A deficiency. The patient has had DKA: diabetic ketoacidosis diagnostic approach to recurrent routine follow-up with the genetics ECG: electrocardiogram myalgia and rhabdomyolysis in team. The patient was readmitted ED: emergency department children. Arch Dis Child. 2015;100(8): 793–797 with a second episode of severe HPF: high-power field rhabdomyolysis with a peak CK of IV: intravenous 10. Elliott P, Andersson B, Arbustini E, et al. 800 000. However, this episode was LVH: left ventricular hypertrophy Classification of the cardiomyopathies: appropriately recognized early, and RBC: red blood cell a position statement from the European the patient recovered quickly. She is Society of Cardiology Working Group on currently growing and developing Myocardial and Pericardial Diseases. Eur Heart J. 2008;29(2):270–276 normally. REFERENCES 11. Limongelli G, Fratta F. S1.4 1. Dunger DB, Sperling MA, Acerini CL, cardiovascular involvement in Pompe et al; European Society for Paediatric ACKNOWLEDGMENTS disease. Acta Myol. 2011;30(3):202–203 Endocrinology; Lawson Wilkins Pediatric We thank Dewesh Agrawal, MD; Vahe Endocrine Society. European Society for 12. Zeharia A, Shaag A, Houtkooper RH, et al. Badalyan, MD; Kimberly A. Chapman, Paediatric Endocrinology/Lawson Mutations in LPIN1 cause recurrent MD; Fran Cogen, MD; Madan Kumar, Wilkins Pediatric Endocrine Society acute myoglobinuria in childhood. Am MD; Kirtida Mistry, MD; Elizabeth consensus statement on diabetic J Hum Genet. 2008;83(4):489–494

Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 143, number 5, May 2019 7 13. Online Mendelian Inheritance in Man. 15. de Meijer AR, Fikkers BG, de Keijzer MH, 17. Zager RA. Studies of mechanisms and #268200: myoglobinuria, acute van Engelen BG, Drenth JP. Serum protective maneuvers in myoglobinuric recurrent, autosomal recessive. creatine kinase as predictor of clinical acute renal injury. Lab Invest. 1989; Available at: http://omim.org/entry/ course in rhabdomyolysis: a 5-year 60(5):619–629 268200. Accessed January 1, 2018 intensive care survey. Intensive Care 18. Pichler K, Scholl-Buergi S, Birnbacher R, – 14. Michot C, Hubert L, Brivet M, et al. LPIN1 Med. 2003;29(7):1121 1125 et al. A novel therapeutic approach for gene mutations: a major cause of 16. Ward MM. Factors predictive of acute LPIN1 mutation-associated severe rhabdomyolysis in early renal failure in rhabdomyolysis. rhabdomyolysis–the Austrian experi- childhood. Hum Mutat. 2010;31(7): Arch Intern Med. 1988;148(7):1553– ence. Muscle Nerve. 2015;52(3):437– E1564–E1573 1557 439

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Downloaded from www.aappublications.org/news by guest on September 27, 2021 A Healthy Toddler With Fever and Lethargy Neha A. Suri, Colleen W. Meehan and Anjna Melwani Pediatrics 2019;143; DOI: 10.1542/peds.2018-0412 originally published online April 5, 2019;

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