Question 1

A male infant, delivered at 38 weeks' gestation, presents with severe bowing of long bones, blue sclera, and craniotabes at birth. Radiographs show severe generalized osteoporosis, a broad and crumpled long bones, beading ribs, and a poorly mineralized skull. Histologic examination of the long bones revealed the trabeculae of the calcified cartilage with an abnormally thin layer of osteoid, and the bony trabeculae are thin and basophilic. The symptoms observed in the infant are characteristic of which disease?

A) Ehlers-Danlos syndrome
B) Hunter syndrome
C) Hurler syndrome
D) Marfan syndrome
E) osteogenesis imperfecta

osteogenesis imperfecta

Accepted Answer

The symptoms described, such as blue sclera, severe bowing of long bones, and generalized osteoporosis, are characteristic of osteogenesis imperfecta, a genetic disorder affecting collagen synthesis. Osteogenesis imperfecta consists of a group of at least 4 types (mild, extensive, severe, and variable). The disorder is characterized by brittle bones and abnormally thin sclerae, which appear blue owing to the lack of connective tissue. The symptoms arise due to defects in twoa-collagen genes, theCOL1A1andCOL1A2 genes. There have been over 100 mutations identified in these 2 genes. The mutations lead to decreased expression of collagen or abnormal pro1 proteins. The abnormal proteins associate with normal collagen subunits, which prevents the triple helical structure of normal collagen to form. The result is degradation of all the collagen proteins, both normal and abnormal.

Question 2

A 30-month-old child presents with coarse facial features, corneal clouding, hepatosplenomegaly, and exhibiting disproportionate short-trunk dwarfism. Radiographic analysis indicates enlargement of the diaphyses of the long bones and irregular metaphyses, along with poorly developed epiphyseal centers. Other skeletal abnormalities typify the features comprising dysotosis multiplex. The child's physical stature and the analysis of bone development indicate the child is suffering from which of the following disorders?

A) Ehlers-Danlos syndrome
B) Hunter syndrome
C) Hurler syndrome
D) Marfan syndrome
E) osteogenesis imperfecta

Hurler syndrome

Accepted Answer

The symptoms described, such as coarse facial features, corneal clouding, hepatosplenomegaly, and skeletal abnormalities consistent with dysostosis multiplex, are characteristic of Hurler syndrome (Mucopolysaccharidosis type I).  Although multiorgan involvement, liver and spleen enlargement, and skeletal abnormalities are common to all the mucopolysaccharidotic (MPS) diseases, each encompasses features that allow for specific diagnosis. Hurler syndrome is characterized by progressive multiorgan failure and premature death. Hallmark features include enlargement of the spleen and liver, severe skeletal deformity, and coarse facial features (which are associated with the constellation of defects referred to as dysotosis multiplex). The disease results from a defect in a-l-iduronidase activity, which leads to intracellular accumulations of heparan sulfates and dermatan sulfates. The accumulation of these GAGs (glycosaminoglycan) in Hurler syndrome patients severely affect development of the skeletal system leading, primarily, to defective long bone growth plate disruption

Question 3

A 12-month-old female infant exhibits severe developmental delay with associated macrocephaly, dysmorphic facies, hypotonia, and hepatosplenomegaly. Clouding of the corneas is not evident. A pebbly ivory-colored lesion is present over the infant's back. The activity of iduronate sulfatase in the plasma is not detectable. These symptoms are indicative of which type of mucopolysaccharidosis?

A) Ehlers-Danlos syndrome
B) Hunter syndrome
C) Hurler syndrome
D) Marfan syndrome
E) osteogenesis imperfecta

Hunter syndrome

Accepted Answer

The symptoms described, including developmental delay, macrocephaly, dysmorphic facies, hypotonia, hepatosplenomegaly, and the absence of corneal clouding, along with undetectable iduronate sulfatase activity, are indicative of Hunter syndrome (MPS II).  Although multiorgan involvement, liver and spleen enlargement, and skeletal abnormalities are common to all the mucopolysaccharidotic (MPS) diseases, each encompasses specific and unique features. Each different MPS is caused by defects in different enzymes which allows for specific diagnosis. Hunter syndrome is characterized by progressive multiorgan failure and premature death. Hallmark features include enlargement of the spleen and liver, severe skeletal deformity, and coarse facial features (which are associated with the constellation of defects referred to as dysotosis multiplex). Unlike Hurler syndrome, whose symptoms are similar (but more severe), Hunter syndrome does not cause corneal opacities. Hunter syndrome results from a defect in iduronidate sulfatase activity and this activity can be measured in the plasma

Question 4

The migration of cancer cells from a solid tumor to another location in the body is referred to metastasis. This process requires the activity of which of the following enzymes?&#10;A) glycosylhydrolases&#10;B) glycosyltransferases&#10;C) lysosomal hydrolases&#10;D) lysyl hydroxylases&#10;E) matrix metalloproteinases

Accepted Answer

Matrix metalloproteinases (MMPs) are enzymes that degrade extracellular matrix components, facilitating cancer cell invasion and migration during metastasis.  Cell migration requires the hydrolysis of the extracellular matrix (ECM) holding the cells into a tissue or a tumor. The primary enzymes responsible for the degradation and remodeling of the ECM are the matrix metalloproteinases.

Question 5

You are examining a 5-year-old girl with severe psychomotor retardation. Physical examination shows distinct hepatosplenomegaly, corneal clouding, coarse facial features, and short stature. Suspecting a lysosomal storage disease you order a test for lysosomal enzyme activity in a skin biopsy. Results of the test shows deficiency in arylsulfatase B and accumulation of dermatan sulfates in the biopsy cells. Given these symptoms and lab studies, this child is most likely suffering from which of the following disorders?

A) Ehlers-Danlos syndrome
B) Maroteaux-Lamy syndrome
C) Hurler-Scheie syndrome
D) Marfan syndrome
E) Morquio syndrome type B

Accepted Answer

The symptoms and lab findings are consistent with Maroteaux-Lamy syndrome (Mucopolysaccharidosis type VI), which is characterized by a deficiency in arylsulfatase B leading to the accumulation of dermatan sulfate.  Maroteaux-Lamy syndrome is characterized by the lysosomal accumulation of dermatan sulfates as a consequence of deficiencies in the lysosomal hydrolase N-acetylgalactosamine 4-sulfatase (arylsulfatase B). Although mental development proceeds normally in Maroteaux-Lamy patients, the progression of physical and visual impairments ultimately impedes psychomotor abilities. The clinical features and severity in Maroteaux-Lamy patients is variable, but usually include short stature, hepatosplenomegaly, stiff joints, corneal clouding, cardiac abnormalities, facial dysmorphism, and dysotosis multiplex. Hepatosplenomegaly is always present in Maroteaux-Lamy patients after the age of 6. In patients with the most severe forms of the disease there is a shortened trunk, protuberant abdomen, and prominent lumbar lordosis

Question 6

You are studying the production of an extracellular matrix by cultures of fibroblasts isolated from a melanoma. Histological studies demonstrate an absence of merosin. Based upon this finding, which of the following ECM components is most likely not being synthesized or processed appropriately in your cell culture system?

A) collagen
B) elastin
C) fibrillin
D) fibronectin
E) laminin

Accepted Answer

Merosin is a specific isoform of laminin, so an absence of merosin indicates a problem with the synthesis or processing of laminin in the extracellular matrix. Laminins are heterotrimeric proteins that have been found to form at least 15 different types of heterotrimers. Laminin heterotrimers are quite large, ranging from under 500,000 to nearly a 1,000,000 Da in mass. Laminins contain common structural features that include a tandem distribution of globular, rod-like, and coiled-coil domains. The coiled-coil domains are responsible for joining the 3 chains into the characteristic heterotrimeric structure called merosin

Question 7

Some types of malignant cells lack expression of fibronectin. The loss of fibronectin by these cells would most likely be associated with which of the following?&#10;A) decreased production of GAGs found in fibroblast proteoglycans&#10;B) increased adherence of the cells to the basement membrane&#10;C) inhibition of matrix metalloproteinase activation&#10;D) loss of collagen processing in the extracellular matrix&#10;E) reduced integrin-mediated cell adhesion

Accepted Answer

Fibronectin is an extracellular matrix protein that binds to integrins, facilitating cell adhesion. Loss of fibronectin would reduce integrin-mediated cell adhesion. Fibronectin is an ECM glycoprotein that is responsible for interaction with integrins present in the plasma membrane of cells, as well as interactions with collagens and glycosaminoglycans. The loss of functional fibronectin would result in inappropriate intracellular signaling, cell shape changes, and cell movements.

Question 8

A female infant, delivered at 37 weeks' gestation, presents with severe bowing of long bones. Physical examination shows blue sclera and x-rays show broad and crumpled long bones. As the attending physician, you suspect a disorder in connective tissues and order an evaluation of collagen gene defects. Results demonstrate the infant harbors a mutation in theCOL1A1gene. The presenting symptoms and molecular analysis indicate this child is suffering from which of the following disorders?

A) Ehlers-Danlos syndrome
B) Maroteaux-Lamy syndrome
C) Hurler-Scheie syndrome
D) Marfan syndrome
E) osteogenesis imperfecta

Accepted Answer

The symptoms and mutation in the COL1A1 gene are indicative of osteogenesis imperfecta, a disorder characterized by brittle bones, blue sclera, and defects in type I collagen.  Osteogenesis imperfecta consists of a group of at least 4 types (mild, extensive, severe, and variable). The disorder is characterized by brittle bones and abnormally thin sclerae, which appear blue owing to the lack of connective tissue. The symptoms arise due to defects in 2 a-collagen genes, the COL1A1 and COL1A2 genes. There have been over 100 mutations identified in these 2 genes. The mutations lead to decreased expression of collagen or abnormal pro1 proteins. The abnormal proteins associate with normal collagen subunits, which prevents the triple helical structure of normal collagen to form. The result is degradation of all the collagen proteins, both normal and abnormal.

Question 9

You are examining a 10-month-old male infant who exhibits severe developmental delay. The infant also shows macrocephaly, dysmorphic facies, and hepatosplenomegaly. Clouding of the corneas is not evident, so you suspect the infant has a particular form of a lysosomal storage disease and order a test for the activity of iduronate sulfatase in the blood. Results of this test confirm that the enzyme activity is absent. Which of the following would you expect to find at elevated levels in fibroblasts from a skin biopsy from this patient?

A) chondroitin sulfates
B) dermatan sulfates
C) hyaluronates
D) keratin sulfate I
E) keratin sulfate II

Accepted Answer

The absence of iduronate sulfatase activity is indicative of Hunter syndrome, a lysosomal storage disorder. In this condition, dermatan sulfate and heparan sulfate accumulate due to the inability to degrade them properly.  The infant is suffering from Hunter syndrome. This disorder is characterized by the lysosomal accumulation of dermatan and heparan sulfates as a consequence of deficiencies in the lysosomal hydrolase iduronate sulfatase. Iduronate sulfatase (also called iduronate 2-sulfatase) hydrolyzes sulfates from the 2-position of l-iduronate present in dermatan and heparan sulfates.

Question 10

You are examining a 2-year-old child presenting with disproportionate short-trunk dwarfism. Additional physical signs are coarse facial features, corneal clouding, and hepatosplenomegaly. You suspect the child is suffering from a lysosomal storage disease and order a test for a-iduronidase activity and find that it is severely impaired. Which of the following would you expect to find at elevated levels in fibroblasts from a skin biopsy from this patient?

A) chondroitin sulfates
B) heparan sulfates
C) hyaluronates
D) keratin sulfate I
E) keratin sulfate II

Accepted Answer

The symptoms and impaired a-iduronidase activity suggest Hurler syndrome, a type of mucopolysaccharidosis. In this condition, heparan sulfate and dermatan sulfate accumulate due to the enzyme deficiency.  The child is most likely suffering from Hurler syndrome. This disorder is characterized by the lysosomal accumulation of dermatan and heparan sulfates as a consequence of defects in the lysosomal hydrolase a-l-iduronidase.

Question 11

A 12-month-old girl is referred for genetic evaluation because of coarse facial features, an enlarged tongue, hepatosplenomegaly, joint stiffness, and delayed growth and development. She appeared normal at birth except for an umbilical hernia. Urine screening shows increased concentrations of dermatan sulfate and heparan sulfate. The child most likely has a disorder in the lysosomal metabolism of which of the following substances?

A) cholesterol esters
B) glycogen
C) glycosaminoglycans
D) glycosphingolipids
E) spingomyelins

Accepted Answer

The answer of A 12-month-old girl is referred for genetic...

Question 12

An 18-month-old girl is brought to the physician by her parents because of developmental delays since the age of 9 months. She has a history of recurrent otitis media. She underwent bilateral inguinal hernia repair at the age of 12 months. Her vocabulary consists of 2 single words, and she is starting to walk with assistance. She is at the 10th percentile for length and the 25th percentile for weight. Physical examination shows generalized hirsutism, a prominent forehead with full cheeks, cloudy corneas, a depressed nasal bridge, and rhinorrhea. There is moderate hepatomegaly. The catabolism of which of the following is most likely abnormal in this patient?

A) branched-chain amino acids
B) coproporphyrins
C) glycogen
D) glycosaminoglycans
E) phospholipids

Accepted Answer

The answer of An 18-month-old girl is brought to the...

Question 13

A 5-year-old girl has had numerous childhood fractures. She is also found to have blue sclera, hearing abnormalities, and misshapen teeth. Which of the following is the most likely cause of these findings?

A) abnormal intestinal receptors for calcium
B) an inability to metabolize vitamin D
C) inadequate mineralization of bone matrix
D) renal inability to conserve phosphorous
E) synthesis of abnormal type I collagen

Accepted Answer

The answer of A 5-year-old girl has had numerous childhood...

Deck 39: Extracellular Matrix: Glycosaminoglycans and Proteoglycans