A 5-day-old term newborn is brought to the emergency department for multiple episodes of emesis. The breastfed infant has been having fewer wet diapers over the last 2 days. Vital signs show tachycardia, tachypnea, and hypotension. Physical examination shows an icteric, lethargic baby with a sunken fontanelle, dry mucous membranes, and hepatomegaly. A blood culture is drawn and empiric antibiotics are initiated. Hematologic studies show leukocytosis with bandemia. Serum studies show hypoglycemia and elevated transaminases. The ammonia level is normal. Newborn screen is pending. Preliminary results from arterial blood culture show gram-negative rods. The infant is placed on a special formula and gradually improves over the next few days. Which of the following steps in metabolism is most likely impaired in this patient?

Question

A 5-day-old term newborn is brought to the emergency department for multiple episodes of emesis.  The breastfed infant has been having fewer wet diapers over the last 2 days.  Vital signs show tachycardia, tachypnea, and hypotension.  Physical examination shows an icteric, lethargic baby with a sunken fontanelle, dry mucous membranes, and hepatomegaly.  A blood culture is drawn and empiric antibiotics are initiated.  Hematologic studies show leukocytosis with bandemia.  Serum studies show hypoglycemia and elevated transaminases.  The ammonia level is normal.  Newborn screen is pending.  Preliminary results from arterial blood culture show gram-negative rods.  The infant is placed on a special formula and gradually improves over the next few days.  Which of the following steps in metabolism is most likely impaired in this patient?

Quizplus · Accepted Answer

11ec160b_369e_54d2_9249_cdc930b1f2a6_MD0001_00 Lactose (milk sugar) is degraded by lactase, the intestinal disaccharidase, to galactose and glucose. Galactose is then phosphorylated to galactose-1-phosphate by the enzyme galactokinase (GALK). Galactose-1-phosphate is converted to glucose-1-phosphate by epimerization with transfer of uridine diphosphate (UDP) from UDP-glucose to UDP-galactose. This reaction is catalyzed by galactose-1-phosphate uridyl transferase (GALT). UDP-galactose is then epimerized to UDP-glucose by UDP-galactose-4 epimerase. Although GALT deficiency is the most common form, a defect in any of these three enzymes can cause galactosemia. Galactosemia can present with vomiting and lethargy soon after initiation of breastfeeding. In GALT deficiency, toxicity of accumulated galactose-1-phosphate is responsible for impaired liver function (transaminitis, hyperbilirubinemia, hypoglycemia) and renal dysfunction (hyperchloremic metabolic acidosis, aminoaciduria). Patients are also predisposed to Escherichia coli (gram-negative rod) sepsis. Restricting lactose intake (eg, breast milk) and initiation of soy milk-based formula can result in regression of cataracts and improvement in renal and liver function. Soy milk consists of sucrose, which is metabolized to glucose and fructose. Glucose and fructose do not need GALT or GALK to enter the glycolytic pathway and generate energy. (Choice A) Lactase hydrolyzes lactose to galactose in the small intestine. Primary lactase deficiency causes lactose intolerance and is rare in neonates. (Choice B) Aldose reductase converts galactose to galactitol. GALT and GALK deficiency can lead to galactitol accumulation in the lens, which can lead to cataract formation in patients with galactosemia. However, aldose reductase deficiency does not cause galactosemia. (Choice C) GALK phosphorylates galactose and its deficiency typically causes less severe manifestations of galactosemia with cataract formation (due to galactitol) being the most common manifestation. Because galactose-1-phosphate does not accumulate, liver and renal functions are preserved. (Choice E) Phosphoglucomutase isomerizes glucose-1-phosphate to glucose-6-phosphate, which then enters the glycolytic pathway. Its deficiency is rare. In GALT deficiency, accumulation of galactose-1-phosphate blocks phosphoglucomutase, thereby preventing energy production via glycolysis. Educational objective: Classic galactosemia results from deficiency of galactose-1-phosphate uridyl transferase. Clinical features include vomiting, lethargy, jaundice, and Escherichia coli sepsis. Cessation of breastfeeding and switching to soy milk-based formula is recommended. __________ References: Galactosemia: when is it a newborn screening emergency? (http://www.ncbi.nlm.nih.gov/pubmed/22483615)

A 5-Day-Old Term Newborn Is Brought to the Emergency Department