A 2-month-old boy is brought to the emergency department due to progressively worsening "floppiness" and poor feeding. The infant was born in Eastern Europe via an uncomplicated vaginal delivery to a 38-year-old woman and then immigrated to the United States with his family. The parents describe the infant as a "good baby" who rarely cries and sleeps through the night but has lately been difficult to rouse for breastfeeding. Stools have also decreased to every other day and are small and pellet-like. Physical examination shows a hypotonic infant with a large anterior fontanelle, large tongue, and a reducible umbilical hernia. He has low tone and is unable to hold his head erect on his own. No other abnormalities are seen. Which of the following is the most likely cause of this patient's condition?
Congenital hypothyroidism | |
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*Avoid coadministration with soy products, iron, or calcium. | |
Congenital hypothyroidism is one of the most common causes of preventable intellectual disability. Most cases are due to thyroid dysgenesis (agenesis, hypoplasia, or ectopy), and iodine deficiency is a common cause in areas endemic for iodine deficiency (eg, Europe).
Neonates initially have no significant symptoms due to the presence of maternal thyroxine (T4) from transplacental transfer. T4 is responsible for the stimulation of protein synthesis as well as carbohydrate and lipid catabolism in many cells; as maternal T4 wanes, metabolism is impaired and marked by a slowing of physical and mental activity (lethargy, poor feeding, constipation, hypotonia). Accumulation of matrix substances cutaneously and internally results in nonpitting edema (eg, "puffy" face), umbilical hernia, protruding tongue, and a large anterior fontanelle. In addition, T4 is essential for normal brain development and myelination during early life, and infants are at risk of severe and irreversible intellectual disability.
Treatment with levothyroxine by age 2 weeks can normalize cognitive and physical development.
Therefore, universal newborn screening for congenital hypothyroidism is performed in the United States but not in all other countries.
(Choice A) Infants who are fed honey or exposed to spores from the soil are at risk for infantile botulism, which presents with constipation and flaccid paralysis. A large anterior fontanelle, umbilical hernia, and macroglossia are not seen.
(Choice B) Hypotonia and hypothyroidism are features of Down syndrome. However, the absence of other dysmorphic features (eg, upslanting palpebral fissures, bilateral epicanthal folds, single palmar crease) makes Down syndrome unlikely in this patient.
(Choice C) Galactosemia is caused by galactose-1-phosphate uridyltransferase deficiency. Patients with this condition present with jaundice, vomiting, hepatomegaly, and lethargy after ingesting galactose in breast milk or formula in the first few days of life. This patient was previously breastfeeding well and has no hepatomegaly.
(Choice D) Hirschsprung disease is caused by abnormal migration of neural crest cells into the rectosigmoid colon. The lack of ganglion cells in this colon segment impedes gastrointestinal motility, resulting in failed meconium passage and bilious emesis in a newborn.
(Choice F) Phenylketonuria is most commonly caused by phenylalanine hydroxylase deficiency, resulting in hyperphenylalaninemia. It presents with developmental delay, light pigmentation, and a musty body odor.
Educational objective:
Congenital hypothyroidism is usually asymptomatic at birth. After maternal T4 wanes, infants develop constipation, lethargy, hypotonia, macroglossia, an umbilical hernia, and a large anterior fontanelle.