Galactosemia Flashcards
A 5-day-old female is brought to the emergency department with poor feeding, vomiting, lethargy, and jaundice. Physical examination reveals hepatomegaly and bilateral cataracts. Laboratory studies show elevated serum galactose and galactose-1-phosphate levels. The newborn screening test was positive for galactosemia. The infant is started on a lactose-free formula, which resolves her symptoms. Which of the following is the most likely deficient enzyme in this patient?
A) Galactokinase
B) Aldolase B
C) Galactose-1-phosphate uridyltransferase
D) Glucose-6-phosphatase
E) UDP-galactose-4-epimerase
Answer: Galactose-1-phosphate uridyltransferase
Explanation: Classic galactosemia is caused by a deficiency in galactose-1-phosphate uridyltransferase (GALT), leading to the accumulation of toxic metabolites like galactose-1-phosphate and galactitol. This results in symptoms such as failure to thrive, vomiting, diarrhea, hepatomegaly, jaundice, cataracts, metabolic acidosis, and an increased risk of E. coli sepsis in neonates. Early diagnosis through newborn screening and dietary restriction of lactose and galactose is crucial to prevent complications.
Incorrect Answers:
A) Galactokinase deficiency is a milder form of galactosemia and primarily presents with cataracts without systemic symptoms.
B) Aldolase B deficiency is associated with hereditary fructose intolerance, not galactosemia.
D) Glucose-6-phosphatase deficiency causes Von Gierke disease, characterized by severe fasting hypoglycemia and hepatomegaly.
E) UDP-galactose-4-epimerase deficiency can be asymptomatic or present with mild symptoms, depending on the subtype, and does not cause the severe symptoms seen in classic galactosemia.
A 3-day-old male is brought to the pediatric clinic with a history of poor feeding, vomiting, and yellowing of the skin. The parents report that symptoms began shortly after introducing formula. On physical examination, the infant is jaundiced and has hepatomegaly. Laboratory tests show elevated total and direct bilirubin, hypoglycemia, and metabolic acidosis. Newborn screening was positive for galactosemia. Which of the following best explains the pathophysiology of this condition?
A) Impaired conversion of galactose to galactose-1-phosphate
B) Accumulation of galactitol due to galactokinase deficiency
C) Impaired conversion of galactose-1-phosphate to UDP-galactose
D) Depletion of phosphate stores due to aldolase B deficiency
E) Deficient activity of UDP-galactose-4-epimerase
Answer: Impaired conversion of galactose-1-phosphate to UDP-galactose
Explanation: Classic galactosemia is caused by a deficiency of galactose-1-phosphate uridyltransferase (GALT), an enzyme responsible for converting galactose-1-phosphate to UDP-galactose. The accumulation of galactose-1-phosphate is toxic to tissues and disrupts normal metabolic processes, leading to failure to thrive, vomiting, jaundice, hepatomegaly, hypoglycemia, and metabolic acidosis. Early detection through newborn screening and dietary elimination of lactose and galactose is essential to prevent severe complications like sepsis, cataracts, and cognitive impairment.
Incorrect Answers:
A) Impaired conversion of galactose to galactose-1-phosphate is not the defect in classic galactosemia but in galactokinase deficiency.
B) Accumulation of galactitol occurs in galactokinase deficiency, leading to cataracts without systemic symptoms.
D) Depletion of phosphate stores due to aldolase B deficiency is seen in hereditary fructose intolerance, not galactosemia.
E) UDP-galactose-4-epimerase deficiency affects the conversion of UDP-galactose to glucose-1-phosphate, leading to a milder phenotype compared to classic galactosemia.
What are the three types of Galactosemia, and which enzymes are deficient in each?
1) Galactokinase Deficiency (Galactokinase)
2) Classic Galactosemia (GALT; Galactose-1-Phosphate Uridyltransferase)
3) Uridine Diphosphate Galactose-4-Epimerase Deficiency (UDP-Galactose-4-Epimerase)
What is the mode of inheritance for all types of Galactosemia?
Autosomal recessive
What is the relative frequency and severity of Galactokinase Deficiency?
Rare; mild disease severity
What is the relative frequency and severity of Classic Galactosemia?
Common; severe disease severity
What is the relative frequency and severity of Uridine Diphosphate Galactose-4-Epimerase Deficiency?
Rare; mild to moderate disease severity
What are the clinical features of Galactokinase Deficiency?
- Cataracts.
- Pseudotumor cerebri due to accumulation of galactitol in tissues.
- Social withdrawal (no tracking or smiling in infants).
What are the clinical features of Classic Galactosemia?
Loss of Galactose-1-Phosphate Uridyltransferase (GALT) leads to:
- Failure to thrive
- Hypoglycemia
- Vomiting
- Diarrhea
- Cataracts
- Hepatomegaly and jaundice
- Cognitive impairment
- Increased risk of E. coli sepsis (especially in neonates)
What are the clinical features of Uridine Diphosphate Galactose-4-Epimerase Deficiency?
Mostly asymptomatic but may include jaundice, hypotonia, dysmorphic features, and cognitive deficiencies
How is Galactosemia diagnosed?
Newborn screening test (elevated galactose/galactose-1-phosphate in blood).
urine galactose levels (reducing substances).
Enzyme activity levels.
Symptoms associated with labs (i.e. hyperbilirubinemia).
What is the main treatment for Galactosemia?
Complete cessation of lactose-containing feeds and lifelong adherence to a galactose- and lactose-free diet.
Soy diet.
Treat cataracts.
