A 21-month-old previously healthy girl presented to the emergency 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, hyperglycemia, 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.

A 21-month-old girl initially presented to the emergency department (ED) with 2 days of rhinorrhea, poor oral intake, and a fever of 38.5°C. She was diagnosed with acute otitis media and discharged from the hospital on amoxicillin. She presented back to the same ED later that day with continued poor oral intake, decreased urine output, and lethargy. Her parents denied cough, shortness of breath, emesis, diarrhea, rash, seizurelike activity, focal neurologic deficits, head trauma, and ingestion. They stated that the patient had eczema and 1 previous episode of bronchiolitis but was otherwise healthy. Immunizations were up to date.

On examination, she was afebrile with a heart rate at the upper limit of normal (143 beats per minute). Her respiratory rate was 36. She was noted to be pale with sunken orbits; however, her mucous membranes were moist. Bilateral tympanic membranes were normal. On neurologic examination, she was minimally responsive to noxious stimuli and was given a Glasgow Coma Scale score of 9. There was no evidence of meningismus. The remainder of the examination results were within normal limits.

Dr Agrawal, what are your initial thoughts about this patient’s differential diagnosis? What would be your first steps in her diagnostic evaluation and management?

The red flag in this child’s current presentation is the markedly abnormal Glasgow Coma Scale score of 9. Hence, my initial evaluation would be focused on assessing why this child’s mental status is so depressed. The differential diagnosis for depressed mental status in this child includes central nervous system infection, central nervous system trauma and/or bleed, ingestion (diphenhydramine, benzodiazepine, barbiturates, marijuana, opiate, or anticholinergics), electrolyte disturbance (hypoglycemia, acute hyponatremia with cerebral edema, or acute hypernatremia with osmotic demyelination syndrome), and hepatic encephalopathy. In addition, severe acidosis may lead to mental status changes. Severe acidosis in this child may be secondary to dehydration with secondary poor perfusion; impending shock; unmasking an inborn error of metabolism, with the catabolic state being induced by her recent poor oral intake; a new-onset diabetes mellitus presenting in diabetic ketoacidosis (DKA); an intraabdominal catastrophe with associated necrotic bowel; uremia; acute anemia; or ingestion.

As a result, I would order a blood gas test to assess for acidosis, a finger-stick glucose test to rapidly assess for hypoglycemia, a complete blood cell (CBC) count to assess for anemia, a urinalysis to assess for ketosis, a urine toxicology screen to assess for ingested drugs of abuse leading to mental status changes, and a comprehensive metabolic panel (CMP) to assess for electrolyte derangements, uremia, or hepatic dysfunction. I would also assess for hypoxemia using pulse oximetry and order a chest radiograph (CXR) to assess for pneumonia or cardiomegaly. Given the markedly abnormal mental status, I would initiate fluid resuscitation and order a head computed tomography (CT) scan. I would also consider a lumbar puncture to assess for meningitis and/or encephalitis despite the current lack of fever and meningismus.

Initial workup included a finger-stick blood glucose test, a CBC count, a CMP, a blood gas test, lactate, a urinalysis, a urine drug screen, rapid influenza and respiratory syncytial virus tests, a CXR, and a head CT scan. The point-of-care blood glucose was elevated at 221 mg/dL. The CBC count revealed leukocytosis with a neutrophil predominance and bandemia (Table 1). The CMP was significant for hyponatremia, mild hyperkalemia, and elevated urea nitrogen, blood glucose, and transaminases. The blood gas test revealed a mild metabolic acidosis with respiratory compensation. The urinalysis was notable for glucosuria, trace ketones, and large blood with 2 to 5 red blood cells (RBCs) per high-power field (HPF). The urine drug screen result was negative. The rapid influenza and respiratory syncytial virus test results were also negative. The head CT scan and CXR were unremarkable. In addition, blood and urine cultures were collected to evaluate for sepsis, and the patient received 1 dose of ceftriaxone.

TABLE 1

Laboratory Data

TestReferenceTime: 0 hTime: 6 ha
WBC, K/μL 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/μL 214–459 281 262 
Differential, %    
 Segmented neutrophils 13–42 76 81 
 Band neutrophils 0–1 10 
 Lymphocytes 35–67 
 Monocytes 6–16 
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 
Creatinine, 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 
Bilirubin, IU/L <0.8 0.8 0.4 
Alkaline phosphatase, 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 1+ 
 Blood, mg/dL Negative Large 3+ 
 WBC, HPF <6 2–5 
 RBCs, HPF <3 2–5 10 
 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 — 
Amylase, U/L <106 — 
Lipase, U/L 147–199 — 46 
Hemoglobin A1C, % 3.4–6.1 — 5.0 
Ethanol, mg/dL <3.0 — <3.0 
Acetaminophen, μg/mL 0–50 — <2.0 
Salicylate, mg/dL Negative — 3.0 
TestReferenceTime: 0 hTime: 6 ha
WBC, K/μL 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/μL 214–459 281 262 
Differential, %    
 Segmented neutrophils 13–42 76 81 
 Band neutrophils 0–1 10 
 Lymphocytes 35–67 
 Monocytes 6–16 
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 
Creatinine, 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 
Bilirubin, IU/L <0.8 0.8 0.4 
Alkaline phosphatase, 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 1+ 
 Blood, mg/dL Negative Large 3+ 
 WBC, HPF <6 2–5 
 RBCs, HPF <3 2–5 10 
 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 — 
Amylase, U/L <106 — 
Lipase, U/L 147–199 — 46 
Hemoglobin A1C, % 3.4–6.1 — 5.0 
Ethanol, mg/dL <3.0 — <3.0 
Acetaminophen, μg/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.

Dr Cogen, given the elevated serum glucose, glucosuria, ketonuria, and mild acidosis, particularly in the setting of a patient presenting with altered mental status, should we be concerned for DKA?

Given the patient’s presentation, we must consider DKA. However, given that her pH is not <7.3 and her serum bicarbonate is not <15, she does not satisfy the biochemical criteria for the diagnosis of DKA.1 Additionally, with a diagnosis of DKA, one would expect polyuria, not oliguria (as seen with this patient), unless the patient was severely dehydrated or had impending renal compromise. Moreover, even with mild metabolic acidosis, one would expect moderate-to-large ketones. Trace ketonuria, as seen in this patient, could be secondary to starvation; however, the glucose is generally not elevated in starvation ketosis. If there is a concern for diabetes, a hemoglobin A1C should immediately be performed because that will generally confirm the diagnosis. In addition to DKA, other causes of hyperglycemia include medication and stress.

Given the concern for DKA, the patient was initially started on intravenous (IV) fluids and an insulin infusion, with improvement being seen in her hyperglycemia. She was subsequently transferred by air to our tertiary-care facility for further workup and management.

On arrival to our tertiary-care facility’s ED, the insulin infusion was discontinued given a low suspicion for DKA based on initial laboratories. The patient was continued on maintenance IV fluids. Her initial examination was still concerning for altered mental status, although the patient started responding to painful stimuli. A repeat CBC count, CMP, urinalysis, and blood gas test were obtained (Table 1). These repeat laboratories were notable for hypoalbuminemia, significantly elevated transaminases (more than double from before), and large blood on urinalysis with 10 RBCs per HPF. All other previously noted laboratory abnormalities had improved from previous results. Additional laboratories included γ-glutamyl transpeptidase, amylase, lipase, prothrombin time and partial thromboplastin time, hemoglobin A1C, ethanol level, and acetaminophen level (Table 1), with results all being within normal limits. Salicylate level was also obtained and was within the therapeutic range.

Dr Kumar, what specific infectious etiologies are on your initial differential for this patient? In addition to the workup already completed, would you recommend a lumbar puncture?

Given that this patient has elevated transaminases and altered mental status, I am particularly worried about viral encephalitis. Potential etiologies for viral encephalitis include herpes simplex virus, varicella zoster virus, enterovirus, adenovirus, cytomegalovirus, and Epstein-Barr virus. Given that this patient has significantly elevated transaminases, viral hepatitis is also on the differential. Depending on the vaccination history and exposure history, I would consider testing for hepatitis A virus, hepatitis B virus, and hepatitis C virus. In addition, the overall presentation raises some concern for tick-borne illness, including Rocky Mountain spotted fever and ehrlichiosis, which may be present without a corresponding rash. In general, when there is a history of fever and the examination is notable for altered mental status, encephalitis and/or meningitis is a significant concern, and a lumbar puncture is recommended.

A lumbar puncture was initially considered. However, several hours after arrival to the tertiary-care facility, the patient demonstrated increased alertness with ability to respond to questions appropriately. Thus, meningitis and/or encephalitis was considered less likely, and a lumbar puncture was not performed. Given the elevated transaminases, gastroenterology was consulted.

Dr Badalyan, what is your impression of the patient’s significantly elevated transaminases, and is there any further testing you would recommend?

In a patient with altered mental status and elevated liver enzymes, it is important to determine if liver failure is present because it may require a rapid referral to a transplant center. In this child, an essentially normal international normalized ratio and direct bilirubin are reassuring. Elevated transaminases are never used to diagnose liver failure.2 

The differential for elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) in a child with fever and altered mental status is broad and includes sepsis, toxic ingestion, and metabolic disorders. In an older child, I would also consider Wilson disease and autoimmune hepatitis because they can present with fulminant hepatitis.

In this child, it was peculiar that AST was significantly more elevated compared with the ALT (AST/ALT ratio = 4.77). Although ALT is more liver specific, high amounts of AST can be found outside of the liver, including in skeletal or cardiac muscle, RBCs, the kidney, the brain, and the pancreas. Higher AST in this child suggests dysfunction of one of these organs or tissues. Thus, a creatine kinase (CK) level is a useful test. An ammonia level and a complete abdominal ultrasound with Doppler (to evaluate the structure of the liver, portal system, kidneys, and pancreas) are also useful tests.

Dr Agrawal, given these initial laboratory results, is there anything you would add to the differential diagnosis? Are there additional laboratories you would send?

I am intrigued by the urinalysis, which revealed large blood but only 2 to 5 RBCs per HPF. Large blood in the urine in the absence of significant RBCs indicates that either RBCs are being broken down and releasing hemoglobin, which is contributing to hemoglobinuria, or there is myoglobinuria from muscle breakdown. The patient’s elevated transaminases are consistent with rhabdomyolysis, and perhaps profound weakness was the source of what the medical providers misperceived as mental status changes in this sick toddler. Therefore, I would recommend sending a CK level test in the ED to assess whether the large blood noted in the urine is actually myoglobinuria.

An ammonia level test was sent, and the result was normal (46 μmol/L; reference range 29–54 μmol/L). An abdominal ultrasound result was also normal. In addition, a CK level test was sent and was still pending at the time of admission to the hospitalist service. A repeat examination was notable for improved mental status, although the patient had poor movement of extremities in response to nailbed pressure with 2+ strength in the lower extremities and 3+ strength in the upper extremities.

Shortly after arrival on the floor, the patient’s CK value returned at 360 000 U/L (reference range 25–177 U/L).

Dr Melwani, can you share your thoughts about this patient’s differential diagnosis now? What is the differential diagnosis for rhabdomyolysis in a toddler?

The patient’s presentation was evolving and did not adequately match the illness script for a common disease. In general, the differential diagnosis for rhabdomyolysis is extensive and commonly caused by infection, trauma, prolonged muscle activity (exercise or seizures), or medications.3,4 We also considered motor neuron diseases (ie, spinal muscle atrophy), inflammatory myopathies (ie, polymyositis or dermatomyositis), and neuropathies (ie, Guillain-Barre syndrome).5 In addition, we included metabolic myopathies and muscular dystrophies in our differential diagnosis. Although her CK levels were significantly elevated, expected CK levels for each of the above diagnoses are variable and depend on many different factors. In general, the CK level correlates to the degree of muscle injury or damage irrespective of etiology.6 

Virus-induced rhabdomyolysis was considered given that the patient initially presented with fever and rhinorrhea. Dr Kumar, in your experience, can a viral infection lead to such a severe presentation of rhabdomyolysis, or would this be atypical?

Viral infections can cause severe rhabdomyolysis, up to 1000 times the upper limit of normal, but this is rare.7,8 Although influenza and other viruses have been known to cause significant elevations in CK levels, they do not typically cause such marked elevations on their own.7,8 However, marked elevations may be seen in children with an underlying genetic disorder predisposing them to muscle breakdown.

Given that the patient had no identifiable triggers and her CK level was thought to be too high to be secondary to a viral illness alone, the genetics and metabolism team was consulted to evaluate for possible inheritable myopathies.

Dr Chapman, are you worried that this patient might have an inheritable myopathy? If so, which diseases are you most worried about and why? What further testing, if any, would you recommend?

Yes, I am concerned that this patient might have an inheritable myopathy. The differential diagnosis includes long-chain fatty acid oxidation defects, glycogen storage diseases (particularly Pompe disease), muscular dystrophy or congenital myopathies, mitochondrial disorders, lipin-1 deficiency, and exercise-induced rhabdomyolyses, such as McArdle disease, carnitine palmitoyltransferase deficiency, and phosphoglycerate kinase deficiency.9 Given the age of presentation, degree of CK elevation, association with a viral illness, and potassium abnormalities at presentation, lipin-1 deficiency is favored over exercise-induced rhabdomyolyses. Muscular dystrophy and congenital myopathies are less likely in this patient given the absence of a previous history of weakness. Pompe disease is also less likely given that the patient was previously healthy with no history of previous weakness, respiratory distress, or known cardiomegaly; the CK value is also elevated for Pompe disease. A mitochondrial disorder is also lower on the differential given a normal lactate level, an appropriate amount of acidosis for presentation, and the patient’s normal growth and development thus far. A long-chain fatty acid oxidation defect is plausible, although there is no history of hypoglycemia, and the patient’s newborn metabolic screen result was normal.

Regarding further tests, I recommend sending an acylcarnitine profile and tests for serum amino acids and urine organic acids to evaluate for inborn errors of metabolism. I would also order an electrocardiogram (ECG) and consider an echocardiogram to look for evidence of Pompe disease and cardiomyopathy, respectively. Finally, I recommend sending a personalized gene panel to identify mutations in LPIN1, PYGM, CPT2, and PGK1. Mutations in these genes are associated with lipin-1 deficiency, McArdle disease, carnitine palmitoyltransferase II deficiency, and phosphoglycerate kinase deficiency, respectively.

A CXR and an ECG were performed, and cardiology was consulted to evaluate for cardiomyopathy. Dr Tague and Dr Sherwin, is the CXR or ECG suggestive of cardiomegaly?

On CXR, cardiomyopathies can be detected by measuring the diameter of the cardiac silhouette compared with that of the thoracic cavity. Also, examining the cardiac position and contours is helpful to estimate if cardiac chambers are enlarged. It is also important to look closely at the lung fields for any evidence of venous congestion or pleural effusions, which could suggest heart failure.10 

The CXR for this patient was taken on expiration, with only 7 ribs showing above the diaphragm, which can falsely make the heart appear enlarged. However, the cardiac position and lung fields were grossly normal. Therefore, the CXR has no evidence of cardiomegaly.

The ECG should be read systematically. I recommend examining the heart rate, rhythm, and axis first and then looking for any cardiac chamber enlargement, particularly left ventricular hypertrophy (LVH) or right ventricular hypertrophy.

This patient’s history and age was concerning for possible Pompe disease. On ECG, Pompe disease is characterized by a short PR interval (<0.12 seconds) and extreme voltages (LVH).11 The ECG for this patient qualified for borderline amplitudes of the R waves in the precordial leads concerning for possible LVH. However, LVH is less likely because of the insignificant S wave in precordial lead V1 and the lack of Q waves in the inferior precordial leads. In addition, this patient’s PR interval is normal (between 0.12–0.2 seconds), and on both the ECG and CXR, there were no other signs of cardiac chamber enlargement, making Pompe disease unlikely.

An acylcarnitine profile and tests for serum amino acids and urine organic acids were sent and returned within normal limits. A personalized gene panel to look for specific gene mutations in LPIN1, PYGM, CPT2, and PGK1 was also sent and, after discharge from the hospital, returned with positive results for a heterozygous splice-site substitution in the LPIN1 gene. Interestingly, mutations in the LPIN1 gene that result in lipin-1 deficiency are associated with recurrent episodes of rhabdomyolysis in childhood.

This patient’s presentation is typical for autosomal recessive acute recurrent myoglobinuria. Typically, these patients present with recurrent episodes of severe rhabdomyolysis characterized by severe muscle weakness and mental status changes secondary to dehydration and electrolyte abnormalities. Laboratories are notable for significantly elevated CK levels, elevated transaminases, and hematuria. In addition, common electrolyte disturbances include hyperkalemia, hyponatremia, and metabolic acidosis. Hyponatremia is thought to be secondary to the influx of extracellular fluid into the injured muscles. This patient was also noted to have hyperglycemia (likely stress related) as well as leukocytosis (likely due to a combination of inflammation and proinflammatory cytokines as well as hemoconcentration).

Lipin-1 deficiency is an increasingly recognized cause of recurrent rhabdomyolysis in childhood. However, the disease is rare, with ∼40 cases being reported in the literature to date. Children with this disease typically present between 15 months and 7 years of age with episodes of severe rhabdomyolysis and significantly elevated CK levels.9,12 These episodes are typically triggered by fever or mild illness, exercise, fasting, anesthesia, or medications.13 Almost all of the lipin-1 deficiency cases in the literature have presented acutely.9,12,14 These patients are at risk for rapid decompensation and cardiac arrest from arrhythmias secondary to hyperkalemia that may not be apparent on initial presentation. In fact, sudden death from arrhythmias due to hyperkalemia is not uncommon in lipin-1 deficiency. Between acute episodes, affected children have normal strength and exercise capacity, although they are more susceptible to exercise-induced myalgias.14 

Lipin-1 deficiency is, unfortunately, often not diagnosed until after a patient presents with severe rhabdomyolysis. The newborn metabolic screen does not test for many of the metabolic myopathies, including lipin-1 deficiency. Therefore, a clinician must have a high suspicion for lipin-1 deficiency to ensure appropriate diagnosis. If the history or physical examination of a child is notable for pain or weakness, a cardiac arrhythmia, concerning family history, or sudden death of a sibling, a CK level is recommended. Regardless of presenting symptoms or examination findings, a CK level test should also be sent if initial laboratories are notable for elevated transaminases or hematuria. A CK level >100 000 in a previously healthy young child should prompt practitioners to consider ordering molecular genetic tests for metabolic myopathies. Of note, the common screening test results for inborn errors of metabolism (pyruvate, lactate, ammonia, acylcarnitine profile, serum amino acids, and urine organic acids) are usually normal in patients with lipin-1 deficiency.

The mainstays of treatment during acute episodes of rhabdomyolysis are to (1) manage the underlying cause of rhabdomyolysis and halt or ameliorate the process, (2) provide supportive care with aggressive hydration, and (3) closely monitor and correct electrolyte, metabolic, and acid and/or base abnormalities. Correction of hyperkalemia is especially critical because acute hyperkalemia can result in cardiac arrhythmia and ultimately cardiac arrest.

The level of CK elevation in rhabdomyolysis correlates with the severity of skeletal muscle breakdown or injury. The higher the CK level, the higher the plasma myoglobin is expected to be and the higher the risk of acute kidney injury.15 Rhabdomyolysis-associated acute kidney injury is associated with higher mortality.15,16 When urine is acidic, the myoglobin complexes the Tamm-Horsfall protein and precipitates in the tubules, causing obstruction and acute tubular necrosis.17 Therefore, the mainstay of therapy to prevent and treat kidney injury is to aggressively hydrate the patient with a goal to achieve a brisk flow of urine and alkalinization to prevent precipitation.

Typically, aggressive hydration is initiated with normal saline or lactated Ringer solution with the goal of maintaining a urine output of 200 to 300 mL per hour.6 Alkalinization is achieved with a concurrent use of IV sodium bicarbonate to achieve a urine pH >6.0.6 If the patient remains oliguric or anuric despite aggressive hydration, or if the patient continues to have severe electrolyte abnormalities, hemodialysis is then used. In the setting of severe rhabdomyolysis, CK levels should be monitored every 4 to 6 hours, and IV fluids should be continued until CK levels decrease to ≤1000.6 In addition, patients with lipin-1 deficiency should receive high-concentration glucose solutions at the onset of rhabdomyolysis.18 

Parents of children with lipin-1 deficiency should be provided with a letter outlining emergency treatment to ensure that any symptoms of weakness or pain in the setting of illness are worked up rapidly with a high level of suspicion for rhabdomyolysis.13 In addition, patients with lipin-1 deficiency should avoid medications that are known to be associated with rhabdomyolysis, such as statins and certain anesthetics.14 For example, inhaled anesthetics and succinylcholine should be avoided because of their potential to result in muscle breakdown.14 In addition, before any major procedure or anesthesia, dextrose-containing fluids should be administered to prehydrate and block catabolism.18 During these procedures, CK levels should be monitored pre- and intraoperatively as well.

The patient was treated with aggressive hydration and bicarbonate, and her CK level appropriately decreased during her hospitalization (Fig 1). In retrospect, it is likely that the initiation of the insulin infusion may have prevented significant hyperkalemia and cardiac arrest by causing potassium to shift intracellularly. After hospitalization, initial sequencing of the 4 tested genes revealed a heterozygous change in LPIN1, which is typically not associated with disease.13 However, further testing later revealed a second mutation, confirming the diagnosis of lipin-1 deficiency. The patient has had routine follow-up with the genetics team. The patient was readmitted with a second episode of severe rhabdomyolysis with a peak CK of 800 000. However, this episode was appropriately recognized early, and the patient recovered quickly. She is currently growing and developing normally.

FIGURE 1

Patient’s CK level trended over time.

FIGURE 1

Patient’s CK level trended over time.

Close modal

Drs Suri and Meehan contributed to the concept and design of the case report and drafted the initial manuscript; Dr Melwani assisted with the conception of the case presentation and reviewed and revised the manuscript; and all authors approved the final manuscript as submitted.

Permission to present and publish this patient’s case was obtained from the patient’s family.

FUNDING: No external funding.

We thank Dewesh Agrawal, MD; Vahe Badalyan, MD; Kimberly A. Chapman, MD; Fran Cogen, MD; Madan Kumar, MD; Kirtida Mistry, MD; Elizabeth Sherwin, MD; and Lauren Tague, MD, for their numerous contributions to this article. We extend a special thank you to pediatric genetics fellow Charles Billington, MD, for his efforts in helping us communicate with the patient’s family.

ALT

alanine aminotransferase

AST

aspartate aminotransferase

CBC

complete blood cell

CK

creatine kinase

CMP

comprehensive metabolic panel

CT

computed tomography

CXR

chest radiograph

DKA

diabetic ketoacidosis

ECG

electrocardiogram

ED

emergency department

HPF

high-power field

IV

intravenous

LVH

left ventricular hypertrophy

RBC

red blood cell

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Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.