Lysosomal storage diseases Practice Questions

Question 1

An 18-month-old boy is brought in by his parents for a routine check-up. The parents state that the patient still has not had any language development, and they are concerned about developmental delay. Of note, they have also noticed that the patient’s facial features have changed significantly in the last year. The patient also seems to have trouble visually focusing on objects or on the television. On exam, the patient's temperature is 98.2°F (36.8°C), blood pressure is 108/72 mmHg, pulse is 86/min, and respirations are 14/min. Of interest, the patient has not increased much in length or weight in the past 3 months. He is now in the 25th percentile for weight but is in the 90th percentile for head circumference. The patient does not appear to have any gross or fine motor deficiencies. Of note, he has coarse facial features that were not previously noted, including a long face, prominent forehead, and protruding eyes. The patient has corneal clouding bilaterally. At rest, the patient keeps his mouth hanging open. After extensive workup, the patient is found to have 2 mutated copies of the IDUA gene, with no production of the protein iduronidase. Which of the following is the likely mutation found in this disease?

Accepted Answer

Nonsense mutation

Answer

Interstitial deletion

Answer

Silent mutation

Answer

Missense mutation

Answer

Chromosomal translocation

Question 2

A 7-month-old boy is brought by his parents to the pediatrician’s office. His mother says the child has been weakening progressively and is not as active as he used to be when he was born. His condition seems to be getting worse, especially over the last month. He was born at 41 weeks through normal vaginal delivery. There were no complications observed during the prenatal period. He was progressing well over the 1st few months and achieving the appropriate milestones. On examination, his abdomen appears soft with no liver enlargement. The patient appears to be dehydrated and lethargic. The results of a fundoscopic examination are shown in the picture. A blood test for which of the following enzymes is the next best assay to evaluate this patient's health?

Accepted Answer

Hexosaminidase

Answer

Acid alpha-glucosidase

Answer

Sphingomyelinase

Answer

Glucocerebrosidase

Answer

Arylsulfatase A

Question 3

A 2-year-old boy is brought to the emergency department by his parents because of fever and recurrent episodes of jerky movements of his extremities for the past 6 hours. Pregnancy and delivery were uncomplicated, and development was normal until the age of 1 year. The parents report that he has had gradual loss of speech, vision, and motor skills over the past year. During this time, he has been admitted to the hospital three times because of myoclonic seizures. Physical examination shows hypertonicity of the upper and lower extremities. Fundoscopic examination shows pallor of the optic disc bilaterally. An MRI of the brain shows brain atrophy and hyperintensity of the periventricular and subcortical areas. Two days after admission, the patient dies. Histopathologic examination of the brain shows aggregation of globoid cells and loss of glial cells. The patient’s condition was most likely caused by a deficiency of which of the following enzymes?

Accepted Answer

β-Galactocerebrosidase

Answer

β-Glucocerebrosidase

Answer

Arylsulfatase A

Answer

Sphingomyelinase

Answer

β-Hexosaminidase A

Question 4

A deficiency in which of the following lysosomal enzymes is inherited in a pattern similar to a deficiency of iduronate sulfatase (Hunter syndrome)?

Accepted Answer

Alpha-galactosidase A

Answer

Sphingomyelinase

Answer

Glucocerebrosidase

Answer

Galactocerebrosidase

Answer

Alpha-L-iduronidase

Question 5

A 22-year-old man presents to the physician due to a progressively worsening weakness and an increasingly large abdomen. He notes that he eats well and is fairly active; however, his abdomen has become increasingly protuberant. He also complains of easy bruisability. His medical history is not significant and he takes no medications. Physical examination reveals hepatomegaly and splenomegaly. Several bruises can be seen on the inside of his arms and legs. His skin has a yellowish tinge to it. Laboratory testing shows the following:
Hematocrit 25%
Erythrocyte count  2.5 x 106/mm3
Thrombocyte count  25,000/mm3
A bone marrow biopsy shows a crinkled-paper appearance to the macrophages. Which of the following enzymes is most likely deficient in this patient?

Accepted Answer

β-glucosidase

Answer

Arylsulfatase A

Answer

Sphingomyelinase

Answer

α-galactosidase

Answer

Hexosaminidase

Question 6

A 1-year-old boy is brought to his pediatrician for a follow-up appointment. He was recently diagnosed with failure to thrive and developmental delay. His weight is 7 kg (15.4 lb), height is 61 cm (24 in), and head circumference is 42 cm (16.5 in). The patient’s father had a younger sister who suffered from mental and physical delay and died at a very young age. The patient was able to raise his head at the age of 7 months and began to sit alone only recently. He babbles, coos, and smiles to other people. On presentation, his blood pressure is 75/40 mm Hg, heart rate is 147/min, respiratory rate is 28/min, and temperature is 36.4°C (97.5°F). He has a coarse face with small deep orbits, proptotic eyes, big lips, and gingival hyperplasia. His skin is pale with decreased elasticity. His lung and heart sounds are normal. Abdominal examination reveals diminished anterior abdominal wall muscle tone and hepatomegaly. Muscle tone is increased in all groups of muscles on both upper and lower extremities. The physician becomes concerned and performs testing for the suspected hereditary disease. A blood test shows increased lysosomal enzyme concentration in the serum and decreased N-acetylglucosamine-1-phosphotransferase (GlcNAc phosphotransferase) activity within the leukocytes. Which of the statements listed below describes the mechanism of the patient’s condition?

Accepted Answer

The lysosomal enzymes are secreted from the cells instead of being targeted to lysosomes because of lack of mannose phosphorylation on N-linked glycoproteins.

Answer

There is impaired hydrolysis of GM2-ganglioside, which accumulates in the cytoplasm.

Answer

Due to enzyme deficiency, glycogen is extensively accumulated within the hepatocytes.

Answer

The patient’s symptoms are due to dysfunctional metabolism of sphingomyelin, which accumulates within the lysosomes.

Answer

The symptoms result from defective glycolysis, which results in a total energy deficiency.

Question 7

A medical student is studying digestive enzymes at the brush border of the duodenum. He isolates and inactivates an enzyme in the brush border that has a high affinity for the pancreatic proenzyme trypsinogen. When the enzyme is inactivated, trypsinogen is no longer converted to its active form. Which of the following is the most likely underlying mechanism of this enzyme?

Accepted Answer

Cleavage of a propeptide from an N-terminus

Answer

Attachment of a carbohydrate to a side chain

Answer

Phosphorylation of an amino acid side chain

Answer

Carboxylation of a glutamate residue

Answer

Conjugation of ubiquitin to lysine residue

Question 8

A 40-year-old male with Down syndrome is brought to your clinic by his mother. She reports that over the past few months he has started having difficulty managing his daily routine at his assisted-living facility and no longer seems like himself. She says that last week he wandered away from the facility and was brought back by police. Additionally, he has stopped taking his regular antiepileptic medication, and she is concerned that he might have a seizure. TSH is checked and is normal. Which of the following is most likely to be responsible for this man's current presentation?

Accepted Answer

Abnormal protein metabolism

Answer

Premature degradation of a protein

Answer

Hormone deficiency

Answer

Nutritional deficiency

Answer

Expansion of trinucleotide repeats

Question 9

An 8-month-old female infant from a first-degree consanguineous couple was brought to the physician because the mother noticed abnormalities in the growth of her child as well as the different lengths of her child's legs. The infant had gingival hyperplasia, restricted movement in both shoulders, a prominent, pointed forehead, and enophthalmos with a slight opacity in both corneas. A blood test revealed 10 fold higher than normal levels of the following enzymes: N-acetyl-ß-glucosaminidase, ß-glucuronidase, ß-hexosaminidase A, and alkaline phosphatase. Which of the following is most likely deficient in this patient?

Accepted Answer

N-acetyl-glucosamine-1-phosphotransferase

Answer

Lysosomal alpha-1,4-glucosidase

Answer

Glucose-6-phosphate dehydrogenase

Answer

Glucocerebrosidase

Answer

Alpha-galactosidase A

Question 10

A 47-year-old homeless man is brought to the emergency department by police, who found him sleeping by the side of the street. He is somnolent and confused and is unable to give a reliable history. His medical history is unobtainable. Vital signs include: temperature 36.9°C (98.4°F), blood pressure 112/75 mm Hg, and pulse 85/min. Physical examination reveals that he has severe truncal ataxia and horizontal gaze palsy with impaired vestibulo-ocular reflexes. Muscle stretch reflexes and motor strength are normal. He has no sensory deficits. Which of the following best represents the most likely etiology of this patient’s condition?

Accepted Answer

Vitamin B1 deficiency

Answer

Miller-Fisher syndrome

Answer

Vitamin B12 deficiency

Answer

Delirium tremens

Answer

Ethylene glycol intoxication

Lysosomal storage diseases

Study Resources

Lessons

Questions

Flashcards

Lessons

Lysosome structure and function

Sphingolipidoses (Tay-Sachs, Gaucher, Niemann-Pick)

Mucopolysaccharidoses

Oligosaccharidoses

Glycoproteinoses

Lipid storage diseases

Lysosomal enzyme deficiencies

Lysosomal membrane protein disorders

Activator protein deficiencies

Clinical presentation patterns

Diagnostic approaches

Treatment options (ERT, substrate reduction, chaperones)

Genetic counseling for lysosomal diseases

Practice Questions

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About Lysosomal storage diseases for USMLE

Lessons in Lysosomal storage diseases

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