The Journal of Pediatrics
Volume 160, Issue 2 , Page 352, February 2012

Persistence of Fetal Hemoglobin Expression in an Older Child with Trisomy 13

Department of Medicine, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts

published online 01 September 2011.

Article Outline

 

A delayed fetal-to-adult hemoglobin switch occurs in infants with trisomy 13.1, 2, 3 The level of fetal hemoglobin (HbF) has been assessed in very few children with trisomy 13 surviving past infancy.1 A 4-year-old female with trisomy 13 confirmed by karyotype and chromosomal microarray analysis was followed by our complex care service. The patient had developmental delay, a seizure disorder, frequent aspiration requiring gastrostomy tube placement and feedings, and recurrent urinary and respiratory tract infections. She had undergone repair of a cleft palate, umbilical hernia, and polydactyly. She was maintained on a medication regimen of omeprazole, nitrofurantoin, melatonin, and levetiracetam.

A complete blood count showed normal values, with a white blood cell count of 6.06 × 103/μL, hemoglobin value of 11.6 g/dL, and platelet count of 187 × 103/μL. The red blood cell count was 3.84 × 106/μL, with a slightly elevated mean corpuscular volume at 90.3 fL, along with an elevated red cell distribution width of 15.8%, indicative of anisocytosis. HbF was elevated, but hemoglobin A2 was low for age (Figure). Taken together, these findings suggested that the patient had persistence of HbF without signs of anemia or stress erythropoiesis.

  • View full-size image.
  • Figure. 

    A hemoglobin high-performance liquid chromatography tracing showing the levels of various hemoglobins in the blood from a 4-year-old patient with trisomy 13. The levels of HbF and hemoglobin A2 are labeled, and the peaks are shaded in the tracing. The major peak in the center of the tracing is from HbA. The quantification of the peaks is shown with the labels as a percentage of total hemoglobin levels. Normal values at this age are <0.9% for HbF and 2.0%-3.3% for hemoglobin A2. HbA2, hemoglobin A2.

This case demonstrates that patients with trisomy 13 have both a delayed fetal-to-adult hemoglobin switch and persistence of HbF. Given that few children with this syndrome have such long survival, these rare observations are informative.4, 5 Recent work suggests that this phenomenon is attributable to elevated levels of microRNAs 15a and 16-1 produced from the triplicated chromosome 13.6 These observations provide insight into the pathophysiology of aneuploidy syndromes such as trisomy 13, and also suggest avenues by which HbF can be induced therapeutically in patients with hemoglobin disorders.

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References 

  1. Huehns ER, Hecht F, Keil JV, Motulsky AG. Developmental hemoglobin anomalies in a chromosomal triplication: D1 trisomy syndrome. Proc Natl Acad Sci USA. 1964;51:89–97
  2. Walzer S, Gerald PS, Breau G, O’Neill D, Diamond LK. Hematologic changes in the D1 trisomy syndrome. Pediatrics. 1966;38:419–429
  3. Pinkerton PH, Cohen MM. Persistence of hemoglobin F in D/D translocation with trisomy 13-15 (D1). JAMA. 1967;200:647–649
  4. Parker MJ, Budd JL, Draper ES, Young ID. Trisomy 13 and trisomy 18 in a defined population: epidemiological, genetic and prenatal observations. Prenat Diagn. 2003;23:856–860
  5. Rasmussen SA, Wong LY, Yang Q, May KM, Friedman JM. Population-based analyses of mortality in trisomy 13 and trisomy 18. Pediatrics. 2003;111:777–784
  6. Sankaran VG, Menne TF, Scepanovic D, et al. MicroRNA-15a and -16-1 act via MYB to elevate fetal hemoglobin expression in human trisomy 13. Proc Natl Acad Sci USA. 2011;108:1519–1524

PII: S0022-3476(11)00765-7

doi:10.1016/j.jpeds.2011.07.036

The Journal of Pediatrics
Volume 160, Issue 2 , Page 352, February 2012

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