Allergy & Immunology Flashcards
What are TRECs? Associated with?
Severe combined immunodeficiency can be diagnosed on newborn screening by measuring T-cell receptor excision circles (TRECs), which are expressed in T cells of thymic origin. Absence of TRECs indicates low thymic output of T cells.
T-cell receptor excision circles
Small circles of DNA created in T-cells during their passage through the thymus as they rearrange their TCR genes.
Their presence indicates maturation of T cells.
TRECs are reduced in SCID (severe combined immunodeficiency disease).
What unit is used to measure TREC?
What does a high/low value mean?
Cq refers to the number quantification cycles used to quantify the concentration of TRECs in the quantification PCR assay.
A high Cq translates to low TRECs.
What factors affect TREC values?
Factors impacting TREC levels:
Inappropriate collection of NBS, severe illness including sepsis, ECMO (and requirement for significant blood products), cooling, and Down’s syndrome. Prematurity, especially prior to 26 weeks, can be an etiology of positive TREC screens and it is recommended to repeat immune work up when babies are of term.
The newborn screen is meant to identify any child that may have SCID or other T cell lymphopenias via examination of TREC (T-Cell Receptor Excision Circle). A low TREC level does not definitively mean that a baby has SCID or other T cell lymphopenias as false positive screens have been seen.
When is the optimal time to measure thyroid-stimulating hormone and free thyroxine in the neonate at risk for hyperthyroidism?
Between 3 and 5 days of age
Immediately after birth, there is a rise in the concentrations of TSH, thyroxine (T4), and triiodothyronine (T3) in the neonate. Thyroid-stimulating hormone concentration peaks in the first 24 hours after birth and remains elevated for up to 3 to 5 days.
Serum concentrations of T4 and T3 increase up to 6-fold within the first few hours after birth, peaking at 24 to 36 hours of age. Thyroid hormone concentrations gradually decrease to baseline by 3 to 5 days of age.
Even though maternal antithyroid drugs cross the placenta and may delay the presentation of hyperthyroidism, the first TSH and free T4 measurements should still be obtained at 3 to 5 days.
It is recommended that TSH and free T4 measurements be repeated at 10 to 14 days of age, and that the neonate be followed clinically for signs of thyroid dysfunction until at least 2 to 3 months of age.
What is the pathophysiology of transient neonatal Grave’s disease?
Graves disease (GD) is an autoimmune disorder caused by antibodies stimulating the thyroid-stimulating hormone (TSH) receptor —> IgG antibodies cross placenta and lead to activation of the TSH receptor and overproduction of thyroid hormone
When does the fetal thyroid gland first develop?
The fetal thyroid gland develops between 5 and 6 weeks of gestation
When does the fetal thyroid gland start secreting thyroxine?
10 weeks of gestation
When does the fetal TSH receptor begin to function / start secreting TSH?
Fetal thyroid hormone production is limited until 18 to 20 weeks of gestation, when the fetal TSH receptor begins to function. Until that time, the fetus relies on maternal thyroid hormone via transplacental passage.
Features of fetal thyrotoxicosis?
Fetal thyrotoxicosis can manifest as intrauterine growth restriction, fetal tachycardia, craniosynostosis with microcephaly, polyhydramnios or oligohydramnios, hydrops, and/or fetal death.
Polyhydramnios is secondary to fetal goiter and difficulties with swallowing because of esophageal obstruction.
When does neonatal Graves’ disease resolve?
Neonatal GD is a self-limited condition that resolves usually in 3 to 5 months with the clearance of the thyroid receptor antibodies
When do symptoms of neonatal Graves Disease occur?
More than 95% of neonates who will develop symptoms of hyperthyroidism do so in the first month after birth, the majority in the first 2 weeks.
What are symptoms of neonatal Graves Disease?
Signs and symptoms are secondary to excess thyroid hormone and may include:
- tachycardia
- hypertension
- irritability and sleep difficulties
- feeding difficulties with diarrhea
- poor weight gain or weight loss
Severe cases:
- thrombocytopenia
- hepatosplenomegaly with pulmonary hypertension
- cardiac failure
- death, if untreated
A small fontanelle and premature closure of cranial sutures may be found
Presence of any of these signs warrants immediate evaluation of thyroid function.
