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Home , Hypotonia, Neonatal sepsis

and Lethargy in a Two-Day-Old Male Adrienne H. Long, MD, PhD,a,b Jennifer G. Fiore, MD,a,b Riaz Gillani, MD,a,b Laurie M. Douglass, MD,c Alan M. Fujii, MD,d Jodi D. Hoffman, MDe

A 2-day old term male infant was found to be hypotonic and minimally abstract reactive during routine nursing care in the newborn nursery. At 40 hours of life, he was hypoglycemic and had intermittent desaturations to 70%. His mother had an unremarkable and spontaneous vaginal delivery. The mother’s prenatal serology results were negative for infectious risk factors. Apgar scores were 9 at 1 and 5 minutes of life. On day 1 of life, he fed, stooled, and voided well. Our expert panel discusses the differential diagnosis of hypotonia in a neonate, offers diagnostic and management recommendations, and discusses the final diagnosis.

DRS LONG, FIORE, AND GILLANI, birth weight was 3.4 kg (56th PEDIATRIC RESIDENTS percentile), length was 52 cm (87th aDepartment of Medicine, Boston Children’s Hospital, d e percentile), and head circumference Boston, Massachusetts; and Section, Medical A 2-day old male infant born at Genetics Section, cDivision of Child , and 38 weeks and 4 days was found to be was 33 cm (12th percentile). His bDepartment of , Boston Medical Center, Boston, limp and minimally reactive during physical examination at birth was Massachusetts routine care in the newborn nursery. normal for gestational age, with Drs Long, Fiore, and Gillani conceptualized, drafted, Just 5 hours before, he had an appropriate neurologic, cardiac, and and edited the manuscript; Drs Douglass, Fujii, and appropriate neurologic status when respiratory components. The infant Hoffman edited the manuscript; and all authors fi evaluated by the same nurse. He had uneventfully roomed with his mother approved the nal manuscript as submitted and agree to be accountable for all aspects of the work. breastfed once in the interim. during the first 2 days of life. He breastfed well every 2 to 3 hours, with DOI: https://doi.org/10.1542/peds.2018-0788 His mother received routine prenatal good latching during lactation Accepted for publication Dec 18, 2018 care in the United States without assessments. He appropriately stooled Address correspondence to Adrienne H. Long, MD, complications. Prenatal ultrasounds and voided. Routine physical PhD, Department of Pediatrics, Boston Children’s and maternal prenatal serologies were assessments were performed every Hospital, 300 Longwood Ave, Hunnewell Building, unremarkable. His mother had a history 8 hours per protocol, which revealed Pavilion 129, Housestaff Lounge, Boston, MA 02115. E-mail: [email protected] of a positive purified protein derivative a consistently normal physical tuberculin test and was treated for examination including neurologic PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). latent 3 years before. She status. The new finding on day of life 2 had no other medical history. The that he was limp and minimally Copyright © 2019 by the American Academy of Pediatrics parents immigrated from El Salvador reactive represented a significant 1 year before and had not traveled out change from his previous clinical status. FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this of the country since that time. The article to disclose. couple’s first child was a girl who died The pediatric resident on call presented FUNDING: No external funding. in her sleep in El Salvador on the to evaluate the patient. The infant was second day of life of unknown cause. found ill appearing with a temperature POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest The parents denied consanguinity. of 35.4°C, pulse of 110 beats per minute, respiratory rate of 55 beats per to disclose. The patient was born via spontaneous minute, and blood pressure of 92/50 vaginal delivery to a now gravida 2, mm Hg. Oxygen saturation was 94% on To cite: Long AH, Fiore JG, Gillani R, et al. para 2 mother with Apgar scores of 9 room air with intermittent brief self- Hypotonia and Lethargy in a Two-Day-Old Male Infant. Pediatrics. 2018;144(1):e20180788 and 9 at 1 and 5 minutes of life. His resolving desaturations to 70%. He was

Downloaded from www.aappublications.org/news by guest on September 30, 2021 PEDIATRICS Volume 144, number 1, July 2018:e20180788 DIAGNOSTIC DILEMMAS sleepy with a weak cry. He was age, being an infant of a mother with for and and normocephalic with no distinctive diabetes, or having a maternal history provide respiratory support. I would features. On pulmonary examination, of b-blocker usage.1,2 This patient did obtain a point-of-care glucose, he had mild supraclavicular and not have these risk factors. Although complete metabolic panel, complete subcostal retractions with good air the absence of such risk factors is less blood count (CBC) with differential, entry bilaterally. He was diffusely common, it does not exclude the blood cultures, and a lumbar hypotonic with a prominent head lag. possibility that hypoglycemia was the puncture with cerebrospinal fluid The Moro reflex was absent. He had instigating factor that led to the (CSF) studies and culture. Urine a good suck reflex. Palmar grasp and presentation. culture in this setting is of low utility plantar grasp were present but weak. because isolated urinary tract Muscle bulk was normal. He had can also present are exceptionally normal cardiac, abdominal, similarly. Indications of neonatal uncommon in ,1 week old.10 fi dermatologic, and genitourinary sepsis are often nonspeci c and I would empirically start broad- examinations. He had strong radial include poor feeding, lethargy, spectrum antibiotics. Regarding the and femoral pulses and was well temperature instability (including patient’s desaturations and increased perfused throughout. hypothermia), and respiratory work of breathing, I would obtain symptoms. Furthermore, sepsis can a chest radiograph and venous blood lead to hypoglycemia through poor gas. I would tailor respiratory HOW WOULD YOU APPROACH THE feeding and increased metabolic support to the degree of respiratory INITIAL MANAGEMENT OF THIS demands. Although this patient does distress. NEWBORN WITH HYPOTONIA, not have risk factors associated with HYPOTHERMIA, AND DESATURATIONS early neonatal sepsis, namely positive Drs Long, Fiore, and Gillani IN THE NICU? WHAT INITIAL maternal group B streptococcus EVALUATION IS WARRANTED? (GBS) status, prolonged rupture of The infant was transferred to the NICU for further management. Dr Fujii, Neonatology membranes, or elevated maternal intrapartum temperature, sepsis Laboratory studies, including a full The constellation of symptoms, should still be high on the sepsis workup with , including hypotonia, hypothermia, differential.3 Neonatal sepsis occurs were obtained (Table 1). Point-of- and desaturations, is alarming for in 1 in 1000 births and causes 15% of care glucose was 32 mg/dL. The CBC a serious process in this 2-day-old all neonatal deaths.4–6 Furthermore, was reassuring, with a normal white 3 3 infant. Although a broad differential although GBS infections remain the blood cell count for age (16.8 10 m should be considered, the acuity and leading cause of early-onset neonatal cells/ L) and normal immature-to- timing of the presentation can narrow sepsis (∼36%),7 ∼80% of GBS total granulocyte ratio (1%). The CSF the differential to a smaller set of infections occur in patients whose cell count was consistent with more likely diagnoses. For example, mothers had negative perinatal test a mildly traumatic tap without fi had the patient developed symptoms results.8 Thus, this patient warrants signi cant pleocytosis. CSF immediately after birth, hypoxic complete workup for sepsis and chemistries revealed a low glucose of ischemic encephalopathy (HIE) would empirical treatment. 26 mg/dL, consistent with systemic be high on the differential. However, it hypoglycemia and a mildly elevated would be unlikely for HIE to manifest In the general population, other protein of 165 mg/dL. Serum acutely after 48 hours of otherwise diagnoses beyond these are chemistry was normal except for an normal activity. On the basis of significantly rarer. Such diagnoses isolated elevation in aspartate pathophysiology and epidemiology, could include in utero insults, aminotransferase (AST) (432 U/L) hypoglycemia or sepsis would be high neuromuscular disorders, metabolic with a high-to-normal alanine on my differential. and/or genetic disorders, aminotransferase (ALT) (58 U/L). endocrinological issues, and Venous blood gas from the infant was Severe hypoglycemia itself can lead to 9 congenital heart disease. However, unremarkable. His chest radiograph a presentation similar to this infant’s, such diagnoses should remain higher was normal. with altered mental status, poor tone, on the differential in patients such as and an inability to maintain body this who have a positive family Given concern for a possible temperature. Desaturations in this history of infant death. infectious etiology, empirical setting could be explained by , , and acyclovir hypoglycemic seizures. In term Initial management should be focused were started. Dextrose containing infants, common risk factors for on stabilizing the infant and intravenous fluids was provided with hypoglycemia include being small for evaluating the most likely causes of the goal to maintain serum glucose gestational age, large for gestational illness. I would start with evaluation .65 mg/dL. Within 6 hours, the

Downloaded from www.aappublications.org/news by guest on September 30, 2021 2 LONG et al TABLE 1 Initial Laboratory Evaluation (Day of Life 2) central versus peripheral hypotonia Laboratory Study Normal Values11 Test Result can help narrow the differential. To CBC do this, it is important to determine if WBC count, 103 cells per mL 9.4–34 16.8 the infant has hypotonia and/or Polymorphonuclear cells, % — 78 weakness.13 Hypotonia refers to Lymphocytes, % — 15 decreased resistance to stretch, — Monocytes, % 6 whereas weakness refers to Immature granulocytes,a % — 0.8 Immature-to-total granulocyte ratio, % ,30 1 decreased muscle strength. Central Hematocrit, % 56 53.5 hypotonia is accompanied by Platelet count, 103 cells per mL 192 271 increased DTRs and often altered CSF mental status. Weakness with central RBC count, cells per mL — 1350 m – hypotonia is less apparent at this age WBC count, cells per L012 8 ’ Protein, mg/dL 56–102 165 because the newborn s movements Glucose, mg/dL 34–119 26 are less controlled by the cortex. HSV PCR — Negative Examples of central etiologies include Blood gas structural abnormalities such as pH 7.29–7.45 7.41 cerebral malformation, HIE, and PCO2,mmHg 27–40 33.3 Base excess, mM 23.8 to 14.2 23 stroke. In contrast, peripheral Chemistry hypotonia is associated with Sodium, mM 130–145 143 noticeable weakness, which may Potassium, mM 3.7–5.9 5.2 present as a weak cry, a weak grasp, Chloride, mM 97–108 107 a reduced Moro response, or Bicarbonate, mM 17–24 18 Albumin, g/dL 3–3.9 3.3 decreased antigravity movements. , total, mg/dL ,11.5 5.9 These infants are often more alert. AST, U/L 47–150 432 Examples for peripheral hypotonia ALT, U/L 13–45 58 include , Alkaline phosphatase, U/L 150–420 131 congenital muscular dystrophies, and — HSV, herpes simplex virus; PCR, polymerase chain reaction; RBC, red blood cell; WBC, ; , not applicable. congenital or metabolic . a Immature granulocytes represents either metamyelocytes, myelocytes, and/or promyelocytes. Overall, central hypotonia is significantly more common than infant’s clinical status significantly setting of a normal CBC. However, an peripheral hypotonia in neonates. improved, though did not completely infectious etiology could not be ruled normalize. His lethargy, hypothermia, out; thus, the patient remained on After resolution of his hypoglycemia, and hypoglycemia completely empirical antibiotics. Importantly, the this patient had persistent neurologic resolved. He had no additional infant’s persistent, albeit mild, findings consistent with both central hypoxic episodes and the increased abnormalities on neurologic (increased DTRs) and peripheral work of breathing resolved. The examination in the setting of hypotonia (mild weakness and diffuse hypotonia observed on euglycemia prompted consideration normal mental status). In this setting, previous examinations was improved, of additional underlying causes that one should consider mixed muscle- although he still had a slightly led to his acute decompensation, such etiologies, such as congenital increased head lag, incomplete Moro as neurologic and metabolic muscular dystrophies or metabolic reflex, slightly increased deep tendon etiologies. disorders. reflexes (DTRs), and mildly weak palmar grasp. There was no evidence Timing of when the infant developed of muscle fasciculations. WHAT WOULD BE THE NEUROLOGIC AND hypotonia also provides important METABOLIC DIFFERENTIAL DIAGNOSIS information. The acute change in his The infant’s rapid clinical FOR THIS PATIENT? tone makes cerebral dysgenesis, improvement with the normalization syndromic causes such as Down of his serum glucose strongly Dr Douglass, Neurology syndrome or Prader-Willi syndrome, suggested hypoglycemia contributed The differential diagnosis for or spinal muscular atrophy less likely. to, at least in part, his initial a newborn with hypotonia is broad. The most common causes of sudden decompensation. The rapid timeline The localization can be anywhere onset hypotonia in a newborn are for improvement was also thought to along the neural axis: the brain, spinal toxic, metabolic, or infectious. be less consistent with sepsis for an cord, nerve, , Muscular conditions tend to have an underlying etiology, especially in the or muscle.12 However, identifying insidious onset.

Downloaded from www.aappublications.org/news by guest on September 30, 2021 PEDIATRICS Volume 144, number 1, July 2018 3 Dr Hoffman, Genetics circumstances. Such tests have high blood cells on microscopic Syndromic causes of hypotonia are sensitivity and are excellent screening examination (Table 2). Together, important to explore. Prader-Willi studies for many inherited metabolic these studies were highly suggestive fi syndrome can present as hypotonia diseases. In many states, expedited of signi cant rhabdomyolysis. Further and poor feeding in a newborn testing can be requested for infants assessment of cardiac involvement without overt physical signs of suspected of having metabolic revealed a mild increase in the – a genetic syndrome,14 although I disorders. CK muscle-brain isoform; however, agree that the patient’s acute this was thought to be most likely decompensation may make such Drs Long, Fiore, and Gillani cross-reactivity in the setting of significantly elevated total CK levels syndromes less likely. Metabolic Given concerns for possible (cardiac index 0.5%) (Table 3). disorders can certainly cause neurologic or metabolic etiologies, Reassuringly, there was no associated hypotonia and hypoglycemia in further imaging and blood studies increase in troponin I, and an a neonate. Thinking about metabolic were pursued. A head ultrasound echocardiogram was normal. Renal causes, I like the approach outlined was unremarkable. Metabolic 15 function did not appear significantly by Saudubray et al, which identifies laboratories were drawn in the impaired because the infant’s 3 broad categories: disorders of context of resolving hypoglycemia creatinine was not elevated beyond intoxication, disorders of energy (Tables 2 and 3). These studies were what would be expected 48 hours metabolism, and disorders of complex notable for a significant elevation in after birth. molecules. CK to .38 000 U/L (upper limit of normal for age is ∼800 U/L). Disorders of intoxication are due to Urinalysis showed trace ketones. problems with the use of basic Ammonia, lactate, and thyroid HOW DO THE ADDITIONAL STUDIES nutrients and include amino acid and NARROW THE DIFFERENTIAL? studies were normal. An expedited urea cycle disorders, organic New England Newborn Screen was acidemias, and disorders of metal Dr Douglass sent. Plasma and urine amino acids, intoxication. The toxic metabolites Given the degree of CK elevation, urine organic acids, plasma resulting from these disorders can a congenital acylcarnitines, and urine acylglycines lead to a worsening clinical picture comes to the top of the neurologic were sent and were anticipated to over time. Disorders of energy differential. These can have related take several days before the results metabolism are due to problems with would be known. energy production and use; examples malformations and can be consistent include mitochondrial disorders, In addition to the significantly with this patient’s mixed peripheral/ disorders of gluconeogenesis and elevated CK, recall that the infant had central hypotonia. Pure central glycogen storage, pyruvate an isolated elevation in AST without nervous system diagnoses are much metabolism disorders, and disorders a similar increase in ALT (Table 1). less likely at this point. Inborn errors of fatty acid oxidation. Finally, Bagged urinalysis revealed 31 blood of metabolism, however, are also on disorders of complex molecules on dipstick without an increase in red the differential. include entities such as lysosomal and peroxisomal disorders; these tend to be rarer overall. TABLE 2 Metabolic Laboratory Evaluation Laboratory Study Normal Values11 Test Result In the short-term, laboratories that would help explore the broad Serum metabolic studies Glucose, mg/dL 50–90 80 differential under inborn errors of Lactate, mM 1.1–3.5 2.1 metabolism are urinalysis for Ammonia, mM56–92 49 assessment of urine ketones, creatine CK, U/L 145–1578 .38 000 kinase (CK), ammonia, and lactate. Thyroid stimulating hormone, mIU/mL 2.43–24.3 3.27 – Blood amino acids, acylcarnitines, T4, ng/dL 0.94 4.39 1.16 Urinalysis (bag specimen) urine organic acids, and acylglycines Protein Negative 21 would be helpful, but results would Ketone Negative Trace not be available immediately. Blood Negative 31 Leukocyte esterase Negative Negative Dr Fujii Bacteria Negative Positive RBC count, cells per HPF 0–30–3 State newborn screenings are also WBC count, cells per HPF 0–56–10 extremely useful in these HPF, high-power field; RBC, red blood cell; T4, thyroxine; WBC, white blood cell.

Downloaded from www.aappublications.org/news by guest on September 30, 2021 4 LONG et al TABLE 3 Evaluation of Rhabdomyolysis very long-chain acyl coenzyme A Laboratory Study Normal Values11 Test Result dehydrogenase deficiency (VLCADD), CK, U/L 145–1578 45 197 a fatty acid oxidation disorder as CK–muscle-brain, ng/mL — 235 suspected above. Confirmation Cardiac index, % 2.5 0.5 plasma acylcarnitine profile (Fig 2) Troponin I, ng/mL ,4.8 0.027 revealed marked elevation in long – Urea nitrogen, mg/dL 2 19 16 and very long-chain acylcarnitine Creatinine, mg/dL 0.3–1.0 0.6 species (C12-C18), including — , not applicable. tetradecenoylcarnitine (C14:1), the most characteristic metabolic marker Dr Hoffman for renal protection in this patient of VLCADD. Ultimately, genetic fi fi With regard to the inborn errors of with signi cant rhabdomyolysis is sequencing con rmed the VLCADD metabolism, the patient appears also critical. diagnosis by identifying mutations in ACADVL relatively hypoketotic. It is important both alleles of the gene. to note that urine ketones can be Drs Long, Fiore, and Gillani challenging to interpret in the Given concern for a fatty acid FINAL DIAGNOSIS newborn period because many oxidation disorder, breast milk and infants poorly produce ketones. formula were restricted to eliminate VLCADD is a rare autosomal recessive However, this patient’s low ketones in fat from the diet, pending results of condition caused by mutations in the the setting of hypoglycemia and the metabolic workup. The patient ACADVL gene, resulting in significant rhabdomyolysis moves was maintained on dextrose adeficiency in the rate-limiting step metabolic disorders such as fatty acid containing intravenous fluids. The CK of fatty acid b-oxidation for long- oxidation disorders much higher on substantially downtrended with these chain fatty acids.16 The prevalence is the differential. However, this degree measures (Fig 1), which suggested reported to be 1 in 30 000 to 100 000 of rhabdomyolysis in the early that an underlying people.17 and cardiac newborn period would be an atypical (in which muscle damage was muscle rely on fatty acid b-oxidation presentation. Severe rhabdomyolysis abrogated by limiting feeds) may be for energy. During a fasting state typically is a dominant feature of fatty more likely than a muscular when glycogen stores are depleted, acid oxidation disorders that present dystrophy. Throughout this time, the patients with VLCADD cannot in adolescence rather than in infancy. infant continued to be well appearing, mobilize energy from fat stores, Although metabolic causes are now with only mildly persistent hypotonia leading to hypoketotic hypoglycemia, high on the differential, additional and slightly increased DTRs. There lethargy, and muscle damage. Buildup testing is necessary to make the final were no additional episodes of of toxic long-chain fatty acid diagnosis. lethargy, profound hypotonia, precursors leads to multiorgan hypothermia, or hypoglycemia. damage affecting the liver, heart, and skeletal muscle. HOW DO YOU ADDRESS THE SAFETY OF On day of life 4, the New England FEEDING AN INFANT WHEN METABOLIC Newborn Screen resulted with an There are 3 typical phenotypes DISORDERS ARE ON THE DIFFERENTIAL? increase in very long-chain described in patients with acylcarnitine species concerning for VLCADD.18 The most severe form Dr Hoffman presents in early infancy and is When an inborn error of metabolism characterized by hypoglycemia, is suspected, caution with feeding is hypotonia, cardiomyopathy, necessary. One must be mindful that arrhythmias, and hepatomegaly. in disorders of intoxication, toxic Patients with this severe early-onset metabolites upstream of the blocked presentation are at risk for metabolic pathway can impair organ multiorgan failure and fatal function. Thus, it is critical to remove arrhythmias. The second form is the nutrient suspected to be characterized by hypoketotic precipitating the illness. In the case of hypoglycemia and hepatomegaly, suspected fatty acid oxidation without cardiac involvement, and disorders, it is imperative to remove typically presents in early childhood. FIGURE 1 fats from the diet and provide the Infant’s serum CK levels over time after enteral The third form is characterized by patient with glucose as an immediate feeds were restricted to eliminate fat from diet exercise intolerance and source of energy. Ongoing hydration on day of life 3. rhabdomyolysis without

Downloaded from www.aappublications.org/news by guest on September 30, 2021 PEDIATRICS Volume 144, number 1, July 2018 5 FIGURE 2 Infant’s serum acylcarnitine profile on day of life 3. Serum concentrations were divided by the upper limit of normal to show fold increase above the normal range. Cx:y, x carbons in the fatty acid chain with y number of unsaturation sites; DC, dicarboxylic acid; OH, hydroxylation. hypoglycemia and can present in gastrostomy tube can be considered possible that built-up toxic later childhood or even adulthood. to assist with the management of metabolites contributed to both the minor illnesses. All care should be rhabdomyolysis and central deficits in Long-term prognosis is closely tied to provided in consultation with this patient. the severity of the initial presentation a metabolism specialist. and subsequent metabolic The patient from this case remained decompensations. Patients with the in the NICU until day of life 10. After The patient featured in this case is severe early-onset form of VLCADD diagnosis of his underlying metabolic unique in that he had a severe and have the poorest prognosis because disorder, appropriate enteral feeds early clinical presentation with of the risk for fatal cardiac (low in LCT and high in MCT) were significant rhabdomyolysis yet did manifestations. restarted to provide complete not exhibit any cardiac involvement. nutrition required for growth and Patients with all forms of VLCADD are His initial presentation of hypotonia, development. He was ultimately counseled to adhere to a diet low in hypoglycemia, and intermittent advanced to a regimen of 50% breast long-chain triglycerides (LCTs), avoid desaturations appropriately raised milk and 50% formula rich in MCT. prolonged fasting, and avoid concern for sepsis or symptomatic His CK levels continued to dehydration to prevent complications hypoglycemia. The family history of downtrend. The infant had such as symptomatic hypoglycemia, infant death and persistent a transient, mild increase in his serum metabolic acidosis, and neurologic abnormalities were troponin T which self-resolved. Serial rhabdomyolysis.19 Even mild important pieces of the history and echocardiograms revealed no cardiac childhood viral illnesses that lead to physical examination that triggered dysfunction throughout his diminished enteral intake can trigger prompt workup for inherited hospitalization. His hypotonia fully catabolism in VLCADD patients. If this explanations of hypotonia. Although resolved. He was discharged from the is suspected, serum glucose, an uncommon presentation in hospital with a strict feeding regimen chemistries, liver function tests, CK, neonates, the identification of (low in LCT and high in MCT), explicit and an electrocardiogram should be rhabdomyolysis ultimately allowed instructions for when to seek medical obtained. Concern for a catabolic the differential diagnosis to be care, and scheduled metabolism state should also prompt hydration narrowed, enabling the team to reach follow-up. with high-dextrose fluids (eg, the final diagnosis of VLCADD and dextrose 10% water with normal provide appropriate management. It The patient was subsequently saline at 1.5 times maintenance) and is interesting to note, however, that admitted to the hospital 4 times in his formula feeds with a high percentage VLCADD is not commonly associated first 8 months of life for viral illnesses of medium-chain triglycerides with increased DTRs, which added to resulting in diminished oral intake (MCTs). Use of a nasogastric tube or the complexity of this case. It is and elevated CK levels. He has

Downloaded from www.aappublications.org/news by guest on September 30, 2021 6 LONG et al otherwise been growing well and clinical outcomes are linked with how labor onset type and gestational age. meeting developmental milestones. fast treatment is initiated. Am J Obstet Gynecol. 2010;202(3): 245.e1–245.e12 He continues to be managed closely Workup and management of infants by a cardiologist and a metabolism/ suspected of metabolic disorders 5. Weston EJ, Pondo T, Lewis MM, et al. The genetics specialist. He has not should be performed in collaboration burden of invasive early-onset neonatal sepsis in the United States, 2005-2008. developed signs of cardiomyopathy. with metabolic specialists. Multiple The family received genetic Pediatr Infect Dis J. 2011;30(11): online resources also exist that can 937–941 counseling; because VLCADD has an assist clinicians in the diagnosis and autosomal recessive inheritance treatment of such patients. These 6. Oza S, Lawn JE, Hogan DR, Mathers C, Cousens SN. Neonatal cause-of-death pattern, the parents were advised include the New England Consortium estimates for the early and late that future offspring would have of Metabolic Programs,21 a 25% chance of being affected with 22 neonatal periods for 194 countries: GeneReviews, Inborn Errors of 2000-2013. Bull World Health Organ. VLCADD and a 50% chance of being 23 Metabolism Knowledgebase, and 2015;93(1):19–28 asymptomatic carriers. the American College of Medical 7. Schrag SJ, Farley MM, Petit S, et al. Genetics and Genomics ACTion Sheets Epidemiology of invasive early-onset and Confirmatory Algorithms.24 CONCLUSIONS neonatal sepsis, 2005 to 2014. Pediatrics. 2016;138(6):e20162013 Evaluating an infant with 8. Stoll BJ, Hansen NI, Sánchez PJ, et al; hypoglycemia or hypotonia is not ABBREVIATIONS Eunice Kennedy Shriver National uncommon in the newborn nursery. ALT: alanine aminotransferase Institute of Child Health and Human For a vast majority of these cases, AST: aspartate aminotransferase Development Neonatal Research inherited metabolic disorders are not CBC: Network. Early onset neonatal sepsis: the underlying cause. Other etiologies CK: creatine kinase the burden of group B Streptococcal such as transient hyperinsulinism, CSF: cerebrospinal fluid and E. coli disease continues. fi Pediatrics. 2011;127(5):817–826 sepsis, or HIE are signi cantly more DTR: deep tendon reflex likely. However, as illustrated in this GBS: group B streptococcus 9. Leyenaar J, Camfield P, Camfield C. A case, metabolic disorders should HIE: hypoxic ischemic schematic approach to hypotonia in remain on the differential, especially encephalopathy infancy. Paediatr Child Health. 2005; – in infants with a family history of LCT: long-chain triglyceride 10(7):397 400 infant death or in term infants with MCT: medium-chain triglyceride 10. Visser VE, Hall RT. 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Downloaded from www.aappublications.org/news by guest on September 30, 2021 8 LONG et al Hypotonia and Lethargy in a Two-Day-Old Male Infant Adrienne H. Long, Jennifer G. Fiore, Riaz Gillani, Laurie M. Douglass, Alan M. Fujii and Jodi D. Hoffman Pediatrics 2019;144; DOI: 10.1542/peds.2018-0788 originally published online June 21, 2019;

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Downloaded from www.aappublications.org/news by guest on September 30, 2021 Hypotonia and Lethargy in a Two-Day-Old Male Infant Adrienne H. Long, Jennifer G. Fiore, Riaz Gillani, Laurie M. Douglass, Alan M. Fujii and Jodi D. Hoffman Pediatrics 2019;144; DOI: 10.1542/peds.2018-0788 originally published online June 21, 2019;

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