Summer Break

PediatricEducation.org is taking a summer break. The next case will be published on August 17, 2020. In the meantime, please take a look at Random Cases or the different Archives and Curriculum Maps listed at the top of the page.

We appreciate your patronage,
Donna D’Alessandro and Michael D’Alessandro, curators

What Are Common Fatty Acid Oxidation Metabolic Disorders?

Patient Presentation
A 4-week-old male came to clinic for his well child visit. He had been a full-term infant with no known problems, but his parents had been called on day 3 of life for a possible fatty acid oxidation defect on his neonatal screening test. The genetic team evaluated him and additional testing had been sent and eventually was negative. He had always been a vigorous feeder and occasionally would have an effortless emesis after feeding. He did have mild jaundice in the first few days of life that resolved. The family history was negative for any neonatal or infant deaths. There was a paternal second cousin who died in a car accident but no unexplained sudden deaths. The mother had 1 previous first trimester spontaneous abortion. The review of systems was negative.

The pertinent physical exam showed a healthy appearing male with growth parameters in the 10-50%. Weight was 25-50%. He had no obvious abnormal stigmata on his face, head or extremities. Cardiac examination had normal S1, S2 without murmurs. Abdominal examination had no masses or hepatosplenomegaly. Tone and strength were normal.

The diagnosis of a healthy male was made. The parents related their story to the pediatrician and noted there had “been a lot of crying” about the possible diagnosis. “I’m still pretty vigilant watching him. I know that he doesn’t have it, but I worry about any little spit up or funny movement. I guess most parents do, and I know I’ll probably stop doing that as he gets bigger,” the mother stated. The pediatrician offered that these reactions were totally normal for a healthy baby, but with any child who has or could have a health problem, it usually makes the parents more concerned.

Discussion
All cells and particularly their mitochondria need an energy source. Glucose is one of the most common ones, but also fatty acids, lactate, pyruvate, ketones, and amino acids. Fatty acids are formed with a carboxylic acid with a long aliphatic carbon chain usually with even numbers of carbon atoms (usually 4-28 most commonly). Most are unbranched and in foods are usually found in the form of esters.

Fatty acids are important energy sources for the heart (50-70%) but also skeletal muscle where resting muscle uses both glucose and fatty acids. During fasting or increased stress fatty acids become a major source of energy in skeletal muscle. Regulation is by several factors including physiological state, organ system, substrate and co-substrate availability (such as oxygen or carnitine), blood supply, hormones, etc. Long-chain fatty acids need the carnitine transfer system to transport the substance across the outer mitochondrial membrane. Medium and short-chain fatty acids enter the mitochondria directly. Therefore carnitine availability and metabolism is vital for long-chain fatty acids metabolism but not for shorter ones.

Health problems occur when there is insufficient energy production and also build up of precursor metabolites.

With the increase and expansion of neonatal screening programs, especially the use of tandem mass spectrometry, in the US, most infants are screened at birth for fatty acid metabolism problems and therefore can be treated very early in life. However patients can present with arrhythmias, Reye’s syndrome like illnesses and/or even sudden death. Other people may not present until later with more exercise fatigue. Symptoms are generally worsened by stress including fasting, exercise, and illness.

Learning Point
Common fatty acid inborn errors of metabolism include:

  • Very-long chain acyl-CoA dehydrogenase deficiency (VLDCASD)
    • Initial step of β-oxidation of long-chain fatty acids for carbon lengths of 14-20
    • ADVL genes (autosomal recessive) with elevated metabolites with carbon chain lengths of 12, 14, and 16
    • Presents in first months of life usually if severe but can present later
      • Heart – cardiomyopathy and arrhythmias
      • Skeletal – hypotonia, later disease often with muscle fatigue and/or rhabdomyolysis
      • Liver – hypoglycemia, hepatomegaly, hyperammonemia, lactic acidosis, elevated transaminases
    • Treatment
      • Frequent feeding, glucose infusion, low fat formulas and increased medium-chain triglycerides
  • Medium-chain acyl-CoA dehydrogenase deficiency (MCAD)
    • **Most commonly diagnosed fatty acid oxidation disorder on neonatal screening
    • Initial step in dehydrogenation of fatty acids for carbon lengths of 4-12
    • ACADM with elevated metabolites with carbon chain lengths of 8 and 10
    • Presents in 3-24 months with “Reye-like” presentation
      • Liver – hypoketotic hypoglycemia, hepatomegaly, elevated transaminase
      • Neurological – lethargy, seizures
      • Sudden death
    • Treatment
        Avoid fasting, frequent feeding, glucose infusion, uncooked starch
  • Short chain acyl-CoA dehydrogenase deficiency (SCAD)
    • ACADS with elevated metabolites with carbon chain lengths of 4
  • Carnitine palmitoyltransferase I
    • CPT1A with elevated carnitine and decreased carbon chain lengths of 16 and 18
    • Presents < 24 months
      • Heart – cardiomyopathy and arrhythmias
      • Liver – hypoketotic hypoglycemia, hepatomegaly, elevated transaminase, hyperammonemia
      • Neurological – lethargy, seizures
      • Sudden death
    • Treatment
      • Carnitine supplementation, avoid fasting, frequent feeding, glucose infusion
  • Carnitine palmitoyltransferase II
    • CPT2 with decreased carnitine and decreased carbon chain lengths of 16 and 18
    • Presents neonatal to first year usually
      • Heart – cardiomyopathy and arrhythmias
      • Liver – hypoketotic hypoglycemia, hepatomegaly
      • Skeletal – hypotonia, later disease often with muscle fatigue and/or rhabdomyolysis
      • Neurological – lethargy, seizures
      • Sudden death
      • Cystic kidneys
    • Treatment
      • Avoid fasting, frequent feeding, glucose infusion, increased medium-chain triglycerides
  • Systematic primary carnitine deficiency
    • SLC22A5 with decreased total carnitine

Questions for Further Discussion
1. What are common presentations for inborn errors of metabolism? A review can be found here
2. What causes hyperammonemia? A review can be found here
3. What are emergency treatment plan elements that needed to be listed for a patient with a suspected or known inborn error of metabolism?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Lipid Metabolism Disorders

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

El-Hattab AW. Inborn errors of metabolism. Clin Perinatol. 2015;42(2):413-439, x. doi:10.1016/j.clp.2015.02.010

Longo N, Frigeni M, Pasquali M. Carnitine Transport and Fatty Acid Oxidation. Biochim Biophys Acta. 2016;1863(10):2422-2435. doi:10.1016/j.bbamcr.2016.01.023

El-Gharbawy A, Vockley J. Defects of Fatty Acid Oxidation and the Carnitine Shuttle System. Pediatr Clin North Am. 2018;65(2):317-335. doi:10.1016/j.pcl.2017.11.006

Fatty acid. In: Wikipedia. ; 2020. https://en.wikipedia.org/w/index.php?title=Fatty_acid&oldid=947595395.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

What Are Some Pediatric Oncological Emergencies?

Patient Presentation
An 8-year-old female came to the hospital ward with fever up to 101.3 F and neutropenia. She was in her maintenance phase of chemotherapy for acute lymphoblastic leukemia and had received her last chemotherapy 3 weeks previously. Despite using granulocyte stimulating medications, she had had several previous hospitalizations for fever and neutropenia and had responded to antibiotics and monitoring without additional complications. She did endorse some mild abdominal pain but no specific nausea, emesis or diarrhea. The review of systems was negative for respiratory problems, other pain, rash, neurological problems or musculoskeletal problems. She was tired, but parents said this was usually true around this time of her chemotherapy cycle. She had some mild mucositis and was being treated with her oral regimen. She was drinking fairly well and urinating well.

The pertinent physical exam showed a slightly pale and tired patient with normal vital signs including a normal blood pressure. Her weight was 24.1 kg (just below 50%) and down 500 grams from her last clinic visit. HEENT showed alopecia. Mild buccal and tongue ulcerations without obvious thrush. She had no other mucositis noted or obvious lymphadenopathy. Her abdominal exam revealed some mild periumbilical tenderness without guarding. There was no pain in McBurney’s point and no costovertebral angle or suprapubic tenderness. She had no obvious masses and no hepatosplenomegaly. Her bladder was not distended. The rest of her examination was normal.

The laboratory evaluation showed a hemoglobin of 10.3 g mg/dL, total neutrophil count of 485, platelets were 130 x 1000/mm2. Other laboratories were normal include electrolytes, liver function tests, amylase and lipase, uric acid and lactate dehydrogenase.

The diagnosis of fever and neutropenia was made. She was started on antibiotics. The senior resident reminded the interns to monitor her closely especially for abdominal pain. “I know that this looks like a usual fever and neutropenia admission, but you never know that. It could always be something else, so watch her belly tonight. If you aren’t sure, just call me. I’d rather hear about it than not,” she reminded them. The patient’s clinical course showed that her abdominal pain resolved and she was released on day 5 after 24 hours fever free and her hematological counts were increasing.

Discussion
Pediatric cancers in the US number about 12,000 per year. After injury, it is the second leading cause of death in children and adolescents. Cancer presentations vary widely, but often begin with non-specific symptoms that continue or progress depending on the location and tumor type. Patients can present with oncological emergencies especially if there are mechanical obstruction such as superior vena cava syndrome or cerebral herniation. More commonly are infections due to immunosuppression. Cancer treatment also causes its own myriad of problems that clinicians need to be aware of to diagnosis and treat, but again they can have insidious or non-specific presentations. Patients often present with a commonly anticipated problem such as fever and neutropenia or abdominal pain, but it may be a sign of something more emergent. Patients not acting right initially, or not responding to treatment as expected, may have another problem.

Learning Point
Pediatric oncological emergencies include:

  • Cardiovascular/Pulmonary
    • Pericardial effusion or tamponade
    • Hemoptysis
    • Infection
    • Pulmonary embolism
  • Gastrointestinal
    • Bowel obstruction or perforation
    • Infection – appendicitis, tyhilitis or neutropenic colitis
    • Intussception
    • Pancreatitis
  • Hematologic
    • Anemia
    • Bleeding
    • Disseminated intravascular coagulation
    • Hyperleukocytosis
    • Leukopenia
    • Thrombocytopenia
    • Thrombosis
    • Transfusion reactions
  • Infection
    • Fever and neutropenia
    • Infection – bacterial, fungus, viral, parasitic
    • Septic shock
  • Metabolic
    • Tumor lysis syndrome
    • Calcium, hypo- or hyper-
    • Phosphate, hyper-
    • Potassium, hyper-
    • Sodium, hypo-
    • Urea, hyper-
  • Mechanical
    • Airway obstruction
    • Cerebral herniation
    • Spinal cord compression
    • Superior vena cava obstruction
    • Other locations that obstruct outflow
  • Neurologic
    • Cerebrovascular accidents
    • Seizures
    • Syndrome of inappropriate antidiuretic hormone
  • Other
    • Medication side effects
    • Medication interactions
    • Organ failure
    • Tumor rupture
  • Other problems, not necessarily are emergencies but can be
    • Dehydration
    • Graft vs host disease
    • Immunosuppression
    • Iron overload
    • Mucositis
    • Pain

Questions for Further Discussion
1. What are the most common pediatric cancers? A review can be found here
2. How do pediatric cancers present?
3. Steroids are used for many problems. What is the problem with using steroids if there is an undiagnosed malignancy?
4. What are PDQs from the National Cancer Institute and how can they be helpful? A review can be found here

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Cancer in Children and Cancer – Living with Cancer.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Prusakowski MK, Cannone D. Pediatric Oncologic Emergencies. Hematol Oncol Clin North Am. 2017;31(6):959-980. doi:10.1016/j.hoc.2017.08.003

Stephanos K, Picard L. Pediatric Oncologic Emergencies. Emerg Med Clin North Am. 2018;36(3):527-535. doi:10.1016/j.emc.2018.04.007

Handa A, Nozaki T, Makidono A, et al. Pediatric oncologic emergencies: Clinical and imaging review for pediatricians. Pediatr Int Off J Jpn Pediatr Soc. 2019;61(2):122-139. doi:10.1111/ped.13755

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

What Causes Early Pregnancy Vaginal Bleeding?

Patient Presentation

A 16-year-old female called into clinic with a history of abdominal pain for 3-4 days. She described pain that was mainly in her lower abdomen and said she was also having some dark brown vaginal discharge that started that morning. The pain was increasing and she was having nausea but no emesis. She was sexually active and was using Depo-Provera® as her method of birth control. Her last shot was 20 weeks previously. She had been tested for sexually transmitted infections at that time too because she had a new partner. She was worried she was pregnant and wanted to know what she should do. She also denied being light headed or feeling like she was going to pass out. She denied any other vaginal discharge before today.

The diagnosis of vaginal bleeding in the setting of possible early pregnancy was made and the patient was referred to the emergency room. In the emergency room, an early intrauterine pregnancy diagnosis was made. She was managed with expectant monitoring and the bleeding resolved. She eventually delivered a healthy baby boy.

Discussion

Pregnancy complications in early pregnancy range from mild to severe. They can include nausea and emesis which often is treated symptomatically, but can cause hyperemesis gravidarum and need hospitalization for intravenous fluids. Mild cramping and slight spotting are not uncommon. Some type of pregnancy bleeding is common with 20-40% of women experiencing it. Women who have early vaginal bleeding have a higher risk of later pregnancy complications.

Pregnancy in adolescents is about 10% of all pregnancies. Adolescent pregnancy can be associated with various problems including higher rates of threatened abortion, pre-eclampsia, Cesarean section, pre-term delivery and lower birth weights. A review can be found here.

Patients with vaginal bleeding need to be evaluated for hemodynamic stability. Young women especially can lose a significant amount of blood before becoming hemodynamically unstable. Physical examination may reveal abdominal tenderness or signs of an acute abdomen such as rigidity, distension and guarding. Vaginal speculum examination helps to determine location of the bleeding. Bimanual examination can help to determine cervical motion or pelvic tenderness, and uterus size. Evaluation includes serum hCG (human chorionic gonadotropin) levels, ultrasound to try to determine if there is an ectopic or intra-uterine pregnancy and other labs such as hemoglobin/hematocrit and type and cross-match for potential transfusion. The patient’s blood type should be obtained if not known and Rh D immunoglobulin given for Rh negative women. Signs of acute abdomen, cervical motion or pelvic tenderness and tissue in the cervical os are usual reasons for surgical and/or gynecological consultation. Patient with threatened abortion are often managed expectantly with most women having complete expulsion of the products of conception within a few weeks. Management of ectopic pregnancy is medical management with medication such as methotrexate or surgical management particularly if the patient is hemodynamically unstable or has signs of a surgical abdomen.

Learning Point
Potential causes of bleeding in early pregnancy include:

  • Ectopic pregnancy – increased risk with mini-pill or intrauterine device, pelvic infection or sexually transmitted infection, previous ectopic pregnancy, use of assisted reproduction for the pregnancy
  • Threatened abortion
  • Endometrial implantation
  • Malignancy
  • Vaginal or cervical polyps
  • Uterine infection
  • Gestational trophoblastic disease
  • Hemorrhoids

Questions for Further Discussion

1. How do you evaluate heavy menstrual bleeding? A review can be found here

2. How do you evaluate and treat dysfunctional uterine bleeding? A review can be found here

3. What are protective factors to help prevent teenage pregnancy?

Related Cases

To Learn More

To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Vaginal Bleeding and Health Problems In Pregnancy.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Breeze C. Early pregnancy bleeding. Aust Fam Physician. 2016;45(5):283-286.

Bleeding in Early Pregnancy. American Family Physician. https://www.ncbi.nlm.nih.gov/pubmed/30702267. Accessed April 13, 2020. 286.

Karatasli V, Kanmaz AG, Inan AH, Budak A, Beyan E. Maternal and neonatal outcomes of adolescent pregnancy. J Gynecol Obstet Hum Reprod. 2019;48(5):347-350. doi:10.1016/j.jogoh.2019.02.011286.

Pontius E, Vieth JT. Complications in Early Pregnancy. Emerg Med Clin North Am. 2019;37(2):219-237. doi:10.1016/j.emc.2019.01.004286.

Author

Donna M. D’Alessandro, MD

Professor of Pediatrics, University of Iowa