Question 1

A 9-month-old child is presented to the emergency room by his parents who report that he has been vomiting and has severe diarrhea. The episodes of vomiting began when the parents started feeding their child cow's milk. The infant exhibits signs of failing to thrive. Laboratory tests show elevated blood galactose, hypergalactosuria, metabolic acidosis, albuminuria, and hyperaminoaciduria. These clinical and laboratory findings are most consistent with which of the following disorders?

A) alkaptonuria
B) essential fructosuria
C) hereditary galactosemia
D) Menkes disease
E) von Gierke disease

hereditary galactosemia

Accepted Answer

The symptoms and laboratory findings are consistent with hereditary galactosemia, a disorder caused by a deficiency in the enzyme galactose-1-phosphate uridyltransferase, leading to elevated blood galactose and associated complications. This patient is suffering from classic (type 1) galactosemia. Type 1 galactosemia occurs as a consequence of mutations in the gene encoding GALT. Classic galactosemia manifests by a failure of neonates to thrive. Vomiting and diarrhea occur following ingestion of milk; hence individuals are termed lactose intolerant. Clinical findings include impaired liver function (which if left untreated leads to severe cirrhosis), elevated blood galactose, hypergalactosemia, hyperchloremic metabolic acidosis, urinary galactitol excretion and hyperaminoaciduria. Unless controlled by exclusion of galactose from the diet, these patients can go on to develop blindness and fatal liver damage. Blindness is due to the conversion of circulating galactose to the sugar alcohol galactitol, by an NADPH-dependent aldose reductase that is present in neural tissue and in the lens of the eye.

Question 2

You are examining a patient who complains of gastric discomfort following the consumption of milk. Additional signs and symptoms include liver and kidney impairment as well as neural involvement. Blood work indicates an increased concentration of galactose-1-phosphate. This patient likely has a defect in which of the following enzymes?

A) fructose-1,6-bisphosphatase
B) galactokinase
C) galactose-1-phosphate uridyltransferase
D) glucokinase
E) ketohexokinase (fructokinase)

galactose-1-phosphate uridyltransferase

Accepted Answer

The symptoms and increased concentration of galactose-1-phosphate suggest a deficiency in galactose-1-phosphate uridyltransferase, leading to classic galactosemia.  This patient is suffering from classic (type 1) galactosemia. Type 1 galactosemia occurs as a consequence of mutations in the gene encoding galactose- 1-phosphate uridyltransferase (GALT). Classic galactosemia manifests by a failure of neonates to thrive. Vomiting and diarrhea occur following ingestion of milk; hence individuals are termed lactose intolerant. Clinical findings include impaired liver function (which if left untreated leads to severe cirrhosis), elevated blood galactose, hypergalactosemia, hyperchloremic metabolic acidosis, urinary galactitol excretion, and hyperaminoaciduria.

Question 3

A defect in which of the following enzymes of galactose metabolism would most likely be associated with hypoglycemia, hepatomegaly, and hyperaminoaciduria?&#10;A) galactokinase&#10;B) galactose-1-phosphate uridyltransferase&#10;C) galactose-4-epimerase&#10;D) phosphoglucomutase&#10;E) UDP-glucose pyrophosphorylase

Accepted Answer

A defect in galactose-1-phosphate uridyltransferase leads to classic galactosemia, which is associated with symptoms like hypoglycemia, hepatomegaly, and hyperaminoaciduria due to the accumulation of galactose-1-phosphate and its toxic effects on the liver and kidneys.  Mutations in the gene encoding galactose-1-phosphate uridyltransferase (GALT) result in classic galactosemia. This disorder manifests by a failure of neonates to thrive. Vomiting and diarrhea occur following ingestion of milk; hence individuals are termed lactose intolerant. Clinical findings include impaired liver function (which if left untreated leads to severe cirrhosis), elevated blood galactose, and hyperaminoaciduria

Question 4

A 5-week-old girl, who appeared to be healthy at birth, develops diarrhea and vomiting a few days after birth. Your current examination reveals that she has hepatomegaly, jaundice, and early cataract formation and is not meeting developmental milestones. You suspect that she has which of the following conditions?

A) galactosemia
B) Hurler syndrome
C) pyloric stenosis
D) Tay-Sachs disease
E) Type I glycogenosis (von Gierke disease.)

Accepted Answer

The symptoms of diarrhea, vomiting, hepatomegaly, jaundice, early cataract formation, and developmental delays in a newborn suggest galactosemia, a metabolic disorder caused by the inability to properly metabolize galactose.  Galactosemia is an autosomal recessive disorder due (in this more common and more severe form of the disease) to a lack of galactose-1-phosphate uridyl transferase. This results in the formation and accumulation of galactose metabolites. If the infant's diet is not modified to exclude milk products, this will result in damage to the liver (fatty change, cholestasis, cirrhosis, liver failure), eyes (cataract formation), and brain (mental retardation).

Question 5

Deficiencies in both galactokinase (GALK) and galactose-1-phosphate uridyltransferase (GALT) result in galactosemia. Which of the following additional symptoms would be useful in a differential diagnosis to confirm GALK deficiency from GALT deficiency?

A) hepatomegaly
B) hypotonia
C) lenticular cataracts
D) lethargy
E) urinary galactitol excretion

Accepted Answer

GALK deficiency specifically leads to the accumulation of galactitol, which causes lenticular cataracts, distinguishing it from GALT deficiency.  Patients with GALK deficiency often present with cataracts that will resolve upon dietary restriction of galactose. However, although patients with classic galactosemia (GALT deficiency) also can develop cataracts, the prevalence among classic galactosemics is markedly less than among GALK-deficient patients due to the extremely high levels of galactitol found in the latter.

Deck 12: Carbohydrates: Galactose Metabolism