Gaucher Disease Flashcards
A 17-year-old boy presents to the clinic with fatigue, bone pain, and easy bruising. He has a history of frequent nosebleeds and recently noticed increasing abdominal fullness. On examination, there is significant hepatosplenomegaly. Laboratory tests reveal anemia, thrombocytopenia, and elevated serum acid phosphatase levels. A bone marrow biopsy shows macrophages with a crumpled tissue paper appearance. Which of the following is the most likely underlying cause of this condition?
A) Deficiency of sphingomyelinase
B) Deficiency of hexosaminidase A
C) Deficiency of glucocerebrosidase
D) Deficiency of arylsulfatase A
E) Deficiency of α-galactosidase A
Answer: Deficiency of glucocerebrosidase
Explanation: Gaucher Disease is caused by a deficiency of glucocerebrosidase, leading to the accumulation of glucocerebroside in macrophages. This results in hepatosplenomegaly, pancytopenia, bone pain, and the characteristic “Gaucher cells” seen on bone marrow biopsy. Type 1 (non-neuropathic) is the most common form and does not involve the central nervous system. Enzyme replacement therapy with recombinant glucocerebrosidase is the mainstay of treatment.
Incorrect Answers:
A) Deficiency of sphingomyelinase causes Niemann-Pick disease, which presents with hepatosplenomegaly and neurologic involvement but lacks the “crumpled tissue paper” macrophages seen in Gaucher disease.
B) Deficiency of hexosaminidase A causes Tay-Sachs disease, characterized by neurologic regression and a cherry-red macula, without hepatosplenomegaly or bone findings.
D) Deficiency of arylsulfatase A causes metachromatic leukodystrophy, which primarily affects the central nervous system with progressive demyelination.
E) Deficiency of α-galactosidase A causes Fabry disease, presenting with acroparesthesia, angiokeratomas, and renal or cardiac complications.
What is the genetic inheritance pattern of Gaucher Disease?
Autosomal recessive inheritance
What enzyme deficiency causes Gaucher Disease?
Deficiency of glucocerebrosidase (β-glucosidase)
What is the primary substrate that accumulates in Gaucher Disease?
Accumulation of glucocerebroside in macrophages
What are the clinical subtypes of Gaucher Disease?
Type 1 (non-neuropathic), Type 2 (acute neuropathic), Type 3 (chronic neuropathic)
What are the common manifestations of non-neuropathic (type 1) Gaucher Disease?
Hepatosplenomegaly, pancytopenia, bone pain, fractures, and avascular necrosis
What are the distinguishing features of neuropathic (type 2 and 3) Gaucher Disease?
Type 2 presents with severe neurologic degeneration in infancy; Type 3 presents with milder neurologic symptoms later in life
How is Gaucher Disease diagnosed?
Enzyme activity assay (low glucocerebrosidase activity) and genetic testing
What is the characteristic histological finding in Gaucher Disease?
Gaucher cells (macrophages with a crumpled tissue paper appearance)
What is the primary treatment for Gaucher Disease?
Enzyme replacement therapy (e.g., recombinant glucocerebrosidase)
What complications are associated with Gaucher Disease?
Bone crises, pulmonary hypertension, and increased risk of hematologic malignancies (e.g., multiple myeloma)
What is the prognosis of Gaucher Disease?
patients can live into adulthood.
