1. A 3-month-old male infant presents with poor feeding, hypotonia, and cardiomegaly on physical exam. Blood tests reveal elevated lactate, uric acid, and creatine kinase levels. Echocardiogram demonstrates hypertrophic cardiomyopathy. A muscle biopsy shows excessive glycogen storage in lysosomes.
Which enzyme deficiency is most likely responsible for this infant’s condition?
A. Glucose-6-phosphatase
B. Debranching enzyme
C. Alpha-1,4-glucosidase (acid maltase)
D. Muscle phosphorylase
E. Phosphofructokinase
Correct Answer: C. Alpha-1,4-glucosidase (acid maltase). The clinical presentation, particularly cardiomegaly, hypotonia, and lysosomal glycogen storage, is consistent with Pompe disease (GSD II), caused by a deficiency of acid maltase.
Incorrect Options:
A. Glucose-6-phosphatase:
A deficiency of this enzyme causes von Gierke disease (GSD I), which primarily results in severe hypoglycemia, hepatomegaly, and metabolic disturbances like lactic acidosis and hyperuricemia, rather than cardiomegaly and hypotonia.
B. Debranching enzyme:
Debranching enzyme deficiency leads to Cori disease (GSD III). While it can cause hepatomegaly and mild hypoglycemia, it generally does not cause significant cardiomegaly or lysosomal storage as seen in Pompe disease.
D. Muscle phosphorylase:
Muscle phosphorylase deficiency is associated with McArdle disease (GSD V), presenting as exercise intolerance, muscle cramps, and myoglobinuria, typically without cardiac involvement or hypotonia in infancy.
E. Phosphofructokinase:
Deficiency in phosphofructokinase causes Tarui disease (GSD VII), which presents similarly to McArdle disease with muscle cramps and myoglobinuria during exercise, not hypotonia and cardiomegaly in infants.
2. A 10-year-old girl presents with fatigue and exercise intolerance. Her mother reports that she experiences muscle cramps and weakness during physical activity, which improve with rest. During exercise testing, her blood lactate levels fail to rise. Genetic testing reveals a mutation affecting muscle phosphorylase. Which glycogen storage disease is most likely in this patient?
A. McArdle disease
B. von Gierke disease
C. Cori disease
D. Andersen disease
E. Hers disease
Correct Answer: A. McArdle disease. The lack of an increase in lactate during exercise and symptoms of muscle cramps and fatigue indicate McArdle disease (GSD V), characterized by a deficiency in muscle phosphorylase.
Incorrect Options:
B. von Gierke disease:
Von Gierke disease (GSD I) results from glucose-6-phosphatase deficiency and mainly affects the liver, causing hypoglycemia, hepatomegaly, and metabolic abnormalities, not muscle cramps or exercise intolerance.
C. Cori disease:
Cori disease (GSD III) is due to debranching enzyme deficiency and typically causes hepatomegaly, mild hypoglycemia, and muscle weakness but lacks the characteristic exercise intolerance and absent lactate response.
D. Andersen disease:
Andersen disease (GSD IV) involves branching enzyme deficiency, leading to hepatomegaly, cirrhosis, and failure to thrive, with minimal impact on muscle exercise tolerance or lactate production.
E. Hers disease:
Hers disease (GSD VI) results from liver phosphorylase deficiency, which causes mild hypoglycemia and hepatomegaly without affecting muscle performance or causing exercise intolerance.
3. A 6-month-old boy presents with recurrent hypoglycemia, hepatomegaly, and elevated blood lactate levels. His parents report that he sweats and becomes irritable when he misses meals. Blood tests show hyperlipidemia and hyperuricemia. A liver biopsy reveals glycogen accumulation.
What is the most likely enzyme deficiency in this patient?
A. Glycogen synthase
B. Glucose-6-phosphatase
C. Lysosomal alpha-glucosidase
D. Branching enzyme
E. Muscle phosphorylase
Correct Answer: B. Glucose-6-phosphatase. The presentation of hypoglycemia, hepatomegaly, hyperlipidemia, and hyperuricemia is consistent with von Gierke disease (GSD I), due to glucose-6-phosphatase deficiency.
Incorrect Options:
A. Glycogen synthase:
Glycogen synthase deficiency would impair glycogen formation and might lead to fasting hypoglycemia, but it does not cause hepatomegaly or the significant metabolic disturbances (lactic acidosis, hyperlipidemia) observed in von Gierke disease.
C. Lysosomal alpha-glucosidase:
This enzyme deficiency causes Pompe disease (GSD II), which presents with cardiomegaly, hypotonia, and muscle weakness due to glycogen storage in lysosomes, rather than hypoglycemia or hyperlipidemia.
D. Branching enzyme:
Branching enzyme deficiency leads to Andersen disease (GSD IV), often causing hepatomegaly and liver dysfunction. It is not associated with hypoglycemia or metabolic abnormalities such as hyperlipidemia or hyperuricemia.
E. Muscle phosphorylase:
Muscle phosphorylase deficiency is seen in McArdle disease (GSD V) and leads to exercise-induced muscle cramps without causing hypoglycemia, hepatomegaly, or metabolic disturbances.
4. A 5-year-old boy with a history of frequent nosebleeds, easy bruising, and joint hypermobility presents with hepatomegaly. Laboratory studies reveal mildly elevated liver transaminases, and his growth rate is below the 10th percentile. Liver biopsy shows abnormal glycogen with few branch points.
What enzyme deficiency is most likely?
A. Debranching enzyme
B. Branching enzyme
C. Muscle phosphorylase
D. Glycogen synthase
E. Phosphorylase kinase
Correct Answer: B. Branching enzyme. Abnormal glycogen with few branch points and hepatomegaly suggest Andersen disease (GSD IV), caused by a deficiency in the branching enzyme.
Incorrect Options:
A. Debranching enzyme:
Debranching enzyme deficiency causes Cori disease (GSD III), leading to hepatomegaly and hypoglycemia, but glycogen in this condition typically has short outer branches, not reduced branching altogether.
C. Muscle phosphorylase:
Deficiency in muscle phosphorylase results in McArdle disease (GSD V), characterized by muscle cramps and exercise intolerance, not hepatomegaly, abnormal glycogen branching, or growth retardation.
D. Glycogen synthase:
Glycogen synthase deficiency affects glycogen formation and could cause hypoglycemia, but it does not result in hepatomegaly or abnormal glycogen branching.
E. Phosphorylase kinase:
Phosphorylase kinase deficiency (GSD IX) affects glycogen breakdown in the liver, leading to mild hepatomegaly and hypoglycemia, but does not result in structurally abnormal glycogen with reduced branching.
5. A 15-year-old male presents with chronic fatigue, mild hepatomegaly, and muscle cramps on exertion. Lab tests show mild fasting hypoglycemia. A biopsy of his liver shows glycogen with abnormally short outer branches. He has a normal response to glucagon administration.
Which enzyme deficiency is most likely responsible for his symptoms?
A. Debranching enzyme
B. Branching enzyme
C. Liver phosphorylase
D. Muscle phosphorylase
E. Glucose-6-phosphatase
Correct Answer: A. Debranching enzyme. This presentation, particularly with glycogen with abnormally short branches and mild hypoglycemia, indicates Cori disease (GSD III), which results from a deficiency in the debranching enzyme.
Incorrect Options:
B. Branching enzyme:
Branching enzyme deficiency causes Andersen disease (GSD IV), which presents with abnormal glycogen lacking branch points, hepatomegaly, and often severe liver disease, not short branches or hypoglycemia.
C. Liver phosphorylase:
Liver phosphorylase deficiency causes Hers disease (GSD VI), which leads to mild hepatomegaly and fasting hypoglycemia but does not cause abnormal glycogen structure with short branches.
D. Muscle phosphorylase:
Muscle phosphorylase deficiency is seen in McArdle disease (GSD V), causing muscle cramps and exercise intolerance without hepatomegaly, hypoglycemia, or abnormal glycogen structure in the liver.
E. Glucose-6-phosphatase:
Glucose-6-phosphatase deficiency causes von Gierke disease (GSD I), which presents with severe hypoglycemia, hepatomegaly, and metabolic issues (e.g., lactic acidosis) without abnormal glycogen structure such as short branches.
