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Gaucher's disease: Case report of mandibular trauma
Gaucher’s disease: Case report of man.dibul-ar trauma Glenn R. Regenye, DMD,a Bruce A. Huberman, DMD,a and Allen B. Itkin, DDS,b Newark. IV.J. UNIVERSITY
HOSPITAL-UNIVERSITY
OF MEDICINE
AND
DENTISTRY
OF NEW
JERSEY
Gaucher’s disease is a disturbance of lipI’d storage that results in the accumulation of histiocytes filled with glucosyl ceramide in various organs and bones. Clinical features include history of epistaxis, hemoptysis, and spontaneous gingival hemorrhage. This articles reviews Gaucher’s disease with reference to its importance to dental practitioners and a case involving mandibular trauma is presented. (ORAL !SURGORAL MED ORAL PATHOL 1992;73:23-26)
G
aucher’s disease is a hereditary disturbance of lipid metabolism, affecting glycosphingolipid storage. The incidence is 1 per 2500 persons,’ and the disease possesses an autosomal dominant inheritance pattern. Gaucher’s disease is due to deficiency of the enzyme glucosyl ceramidase, the enzyme responsible for the cleavage of glucose from glucosyl ceramide, an intermediate in the biosynthesis and degradation of cellular components. Glucosyl ceramide is abundantly found in leukocytes2 and to a lesser degree in the spleen, liver, aorta, lung, intestine, and serum.3 Gaucher’s disease results from accumulation of glucosyl ceramide within the histiocytes of the reticuloendothelial system. These histiocytes, termed Gaucher cells, accumulate in visceral organs such as the spleen, liver, lymph nodes, and bone marrow, particularly in the femur. The disease is divided into three clinical entities referred to as types I, II, and III. Type I, or the chronic visceral form, occurs in adults and is the most common form of Gaucher’s disease, with a wide range of presenting signs and symptoms. Common presenting signs include hepatosplenomegaly, leukopenia, thrombocytopenia, and mild microcytic anemia.’ Radiolucent bone lesions due to Gaucher cell infiltration of the bone marrow is present in up to 75% of patients.’ This infiltration of bone leads to expanded cortices and vascular impairment. 3,4 Although most commonly 9In private practice, Springfield, N.J. bProfessor, Department of Oral and Maxillofacial 7112129762
Surgery.
affecting the femur, involvement of the pelvis, calvarium, vertebrae, and jaw have been reported. L 5 Classic descriptions of the type I patient have not included central nervous system manifestations, although a few cases have been reported. Type II, the acute neuropathic form, usually presents at 3 months of age. Clinical manifestations include feeding difficulties, hepatosplenomegaly, and a variety of neurologic manifestations. Death usually occurs by 2 years of age from respiratory failure related to CNS involvement and, occasionally, primary pulmonary involvement. Type III, the subacute neuropathic form, has the same clinical presentation as the acute form but is delayed until 1 to 2 years of age. Most type III patients die between the ages of 6 and 12 years. A presumptive diagnosis of Gaucher’s disease can be made from a bone marrow aspirate that shows Gaucher cells.6 These cells have a characteristic wrinkled tissue-paper appearance, with a small, round, or ovoid nucleus and abundant cytoplasm. Elevated serum acid phosphatase activity is also seen in patients with Gaucher’s disease. The definitive diagnosis is based on the demonstration of decreased glucocerebrosidase activity from washed leukocyte assays. Treatment of patients who have Gaucher’s disease occasionally requires splenectomy to alleviate the mechanical problems associated with splenomegaly and the possible hematologic abnormalities such as thrombocytopenia and anemia.7s 8 Bony lesions can present a problem for which there is no special treatment. Bones appear less radiopaque 23
24
Regenye, HuGerman, and Itkin
Fig. 1. Occlusal radiograph showing displacedright parasympbysis fracture. because of their extreme porosity; cancellous bone is coarse grained and “worm eaten” in appearance and may show large pseudocystic defects and noticeable thinning of the cortex.’ Lesions of the femoral head may necessitate surgical debridement and possible reconstruction with a prosthesis. No cure is yet available for this disease, but enzyme replacement therapy through kidney transplantation holds some promise for the future.9 GSEREPORT
A 23-year-old white man was admitted to University Hospital’s trauma service after being involved in a motor vehicle accident as a driver. Preliminary assessmentof his injuries included a basilar skull fracture, multiple facial injuries, and orthopedic injuries. The oral and maxillofacial surgery service was consulted regarding the facial injuries that included displaced right parasymphysis, nondisplaced left ramus, and nondisplaced right subcondylar fractures of the mandible (Figs. 1 and 2). Review of the medical history was positive for Gaucher’s disease type I, diagnosed at age 4. The patient had had a splenectomy at the age of 14 years but had no other relevant medical history. Laboratory values included creatine kinase, 629 U/L; lactate dehydrogenase 426 U/L; aspartate aminotransferase, 93 U/L; and alkaline phosphatase, 118 U/L. The initial complete blood cell count showed a white blood cell count of 24,800 cells/mm3, with the presence of macrocytosis and Howell-Jolly bodies.
Fig. 2, Computed tomographic axial radiograph showing right subcondylar fracture (small auro~] and left ramus fracture (large arrow).
After being cleared for general anesthesia, the patient was taken to the operating room for reduction and stabilization of the mandibular fractures. An intraoral open reduction was performed at the mandibular right parasymphysis together with a closed reduction of the remaining mandibular fractures, with good occlusa! results (Fig. 3). Ten days postoperatively an area of fluctuant swelling was discovered in the mucobuccal fold anterior to the right central and lateral incisors. Severe mobility of these teeth was noted, and they were extracted. Culture reports of the drainage revealed penicillin-resistant Staphylococcus aurezls that respondedto clindamycin, 300 mg every 6 hours. Approximately 14 months after the initial injury the patient was seen for complete dental rehabilitation. A threedimensional computed tomographic scan showed excessive lateral bone formation in the area of the previous mandibuiar fractures (Fig. 4). This excessivelateral bone formation in the symphysis was an esthetic concern of the patient. In the operating room, after 1 million U aqueouspenicillin G intravenously, anterior transosseouswires were removed and the bony symphysis recontoured. A 13 mm endosseous implant was then placed with hydroxyapatite augmentation (Fig. 5). The patient continued taking oral penicillin V 500 mg four times daily for 5 postoperative days, The final restoration of the implant was completed with
Volume 73 Number 1
Gaucher’s disease and mandibular
trauma
25
Fig. 3. Panoramic radiograph showing postoperative results after transosseouswire fixation of parasymphysis and closed reduction of left ramus and right subcondylar fractures.
Fig. 4. Three-dimensional computed tomographic radiograph showing excessivelateral bone formation in area of previously treated mandibular symphysis fracture (arrow).
a fixed splinted denture. At a 2-year follow-up from initial injury the patient was doing well and no mandibular changes were noted on radiographs. DISCIJSSION
Fig. 5. Periapical radiograph showing endosseousimplant in place with hydroxyapatite augmentation.
Fewer than 100 cases of Gaucher’s disease of the maxillofacial region have been reported in the literature.7p lo The fundamental abnormality in the condition is defective activity of the enzyme p-glucosidase and the consequent accumulation of the cerebroside-laden cells in the bone marrow. The resultant clinical features come from the pressure of the expanding abnormal cell mass and the normal vascular supply to the affected bone. The reported cases have revealed some relevant areas of concern for
the treating oral and maxillofacial surgeon. Jaw involvement shows osteoporotic defects interdentally. There have been reported cases of apical resorption of teeth. The affected teeth are usually mobile and if extracted the healing alveolus does not fully recover and does not fill with bone. The foremost concern should be the possibility of hemorrhage. A medical history of epistaxis, hemoptysis, or spontaneous gingival hemorrhage should alert the treating doctor to per-
3RAL ?%JRGQRA-?&D .LPRAipATMoL January 1992
form a detailed medical evaluation preoperatively.” Nonsplenectomized patients with Gaucher’s disease are more prone to prolonged bleeding after any surgical manipulation because of their thrombocytopenia.7,11,l2 This problem can usually be alleviated by splenectomy. In our caseno excessivebleeding was noted during two surgical procedures that included manipulation of a fracture and the extraction of two teeth. An increased incidence of postoperative infection has also been reported in patients with Gaucher’s disease.This has been attributed to the disturbance of the reticuloendothelial system.13However, in only one ‘casewas prophylactic antibiotic therapy prescribed.12 In our casethe postoperative infection was present in the area of a compound mandibular fracture that involved mobile teeth. No conclusion regarding the cause of the infection or the role played by Gaucher’s diseasecan be made. The adult chronic visceral form (type I> of Gaucherls diseasepresents the most challenging diagnostic problem for the physician. Patients with type II die early in infancy, and the patients with type III have clinical signs that prompt a physician’s care. A thorough medical history is the key to recognizing the diseasein older children and adults. The patient may volunteer a history of splenectomy, placement of a femoral head prosthesis, or bone pain. The definitive diagnosis is basedon biopsy of any bony lesion and the measurement of the serum acid phosphataseand glucosyl ceramidase levels. A case of mandibular trauma involving a patient with Gaucher’s diseasetype I is presented. The case
revealed a possible decreasein bone re.modeling not been previously reported as an abnormality of this disease. We thank Dr. J. Hupp for his editorial assistance.
1. Stanbury JB, Wyngarden JB, Fredrickson DS. The metabolic 2. 3. 4. 5. 6.
7.
basis of inherited disease. 3rd ed. New York McGraw-Hill, 1972:738-51. Peters SD, Glew RH, Lee RE. Practical enzymology of the sphingolipidases. New York: Alan R Liss, 1977:72-95. Galjaard H. Genetic metabolic: early diagnosis and prenatal analysis. New York: Elsevier North-Holland, 1980:195-203. Schubiner H, Lefourneau M, Murray DL. Pyogenic osteomyelitis versus pseudo-osteomyelitis in Gaucher’s disease. Clin Pediatr 1987;20:667. Bildman B, Martinez M, Robinson LH. Gaucher’s disease discovered by mandibular biopsy. J Oral Surg 1972;JO:SlO. Lee RE, Robinson DB, Glew RH. Gaucher’s disease: modern enzymatic and anatomic methods of diagnosis. Arch Path01 Lab Med 1981;5:102. Bender IB. Dental observations in Gaucher’s disease. ORAL
SURGORAL MED ORALPATHOL 1959;12:546. 8. Salkv B. Kreel I. Gelernt I. Bauer J. Aufses AH Jr. Solenectomy for Gaucher’s disease. Ann Surg 1979;190:592-4. 9. Groth CG, Collste H, Dreborg S, Hakansson G, Lundgren G, Svennerholm L. Attempt at enzyme replacement in Gaucher disease by renal transplantation. Acta Pediatr Stand 1979;68:475-9. 10. Sela R, Rolliack A, Ulmansky M. Involvement of the mandible in Gaucher’s disease. Br J Oral Surg 1972;9:246. 11. Browne WG. Oral pigmentation and root resorption in Gaucher’s disease. J Oral Surg 1977;35:153. 12. Moth WS. Gaucher’s disease with mandibular bone lesions. ORALSURGORAL MEDORALPATHOL 1953;6:1250. 13. Lau MM, Lichtman DM, Hamati YI, et al. Hip arthroplasty in Gaucher’s disease. J Bone Joint Surg [Am] 1981;63A:598. ,
I
Reprint requests: Glenn R. Regenye, DMD 178 Morris Avenue Springfield, NJ 07081
HOSPITAL-UNIVERSITY
OF MEDICINE
AND
DENTISTRY
OF NEW
JERSEY
Gaucher’s disease is a disturbance of lipI’d storage that results in the accumulation of histiocytes filled with glucosyl ceramide in various organs and bones. Clinical features include history of epistaxis, hemoptysis, and spontaneous gingival hemorrhage. This articles reviews Gaucher’s disease with reference to its importance to dental practitioners and a case involving mandibular trauma is presented. (ORAL !SURGORAL MED ORAL PATHOL 1992;73:23-26)
G
aucher’s disease is a hereditary disturbance of lipid metabolism, affecting glycosphingolipid storage. The incidence is 1 per 2500 persons,’ and the disease possesses an autosomal dominant inheritance pattern. Gaucher’s disease is due to deficiency of the enzyme glucosyl ceramidase, the enzyme responsible for the cleavage of glucose from glucosyl ceramide, an intermediate in the biosynthesis and degradation of cellular components. Glucosyl ceramide is abundantly found in leukocytes2 and to a lesser degree in the spleen, liver, aorta, lung, intestine, and serum.3 Gaucher’s disease results from accumulation of glucosyl ceramide within the histiocytes of the reticuloendothelial system. These histiocytes, termed Gaucher cells, accumulate in visceral organs such as the spleen, liver, lymph nodes, and bone marrow, particularly in the femur. The disease is divided into three clinical entities referred to as types I, II, and III. Type I, or the chronic visceral form, occurs in adults and is the most common form of Gaucher’s disease, with a wide range of presenting signs and symptoms. Common presenting signs include hepatosplenomegaly, leukopenia, thrombocytopenia, and mild microcytic anemia.’ Radiolucent bone lesions due to Gaucher cell infiltration of the bone marrow is present in up to 75% of patients.’ This infiltration of bone leads to expanded cortices and vascular impairment. 3,4 Although most commonly 9In private practice, Springfield, N.J. bProfessor, Department of Oral and Maxillofacial 7112129762
Surgery.
affecting the femur, involvement of the pelvis, calvarium, vertebrae, and jaw have been reported. L 5 Classic descriptions of the type I patient have not included central nervous system manifestations, although a few cases have been reported. Type II, the acute neuropathic form, usually presents at 3 months of age. Clinical manifestations include feeding difficulties, hepatosplenomegaly, and a variety of neurologic manifestations. Death usually occurs by 2 years of age from respiratory failure related to CNS involvement and, occasionally, primary pulmonary involvement. Type III, the subacute neuropathic form, has the same clinical presentation as the acute form but is delayed until 1 to 2 years of age. Most type III patients die between the ages of 6 and 12 years. A presumptive diagnosis of Gaucher’s disease can be made from a bone marrow aspirate that shows Gaucher cells.6 These cells have a characteristic wrinkled tissue-paper appearance, with a small, round, or ovoid nucleus and abundant cytoplasm. Elevated serum acid phosphatase activity is also seen in patients with Gaucher’s disease. The definitive diagnosis is based on the demonstration of decreased glucocerebrosidase activity from washed leukocyte assays. Treatment of patients who have Gaucher’s disease occasionally requires splenectomy to alleviate the mechanical problems associated with splenomegaly and the possible hematologic abnormalities such as thrombocytopenia and anemia.7s 8 Bony lesions can present a problem for which there is no special treatment. Bones appear less radiopaque 23
24
Regenye, HuGerman, and Itkin
Fig. 1. Occlusal radiograph showing displacedright parasympbysis fracture. because of their extreme porosity; cancellous bone is coarse grained and “worm eaten” in appearance and may show large pseudocystic defects and noticeable thinning of the cortex.’ Lesions of the femoral head may necessitate surgical debridement and possible reconstruction with a prosthesis. No cure is yet available for this disease, but enzyme replacement therapy through kidney transplantation holds some promise for the future.9 GSEREPORT
A 23-year-old white man was admitted to University Hospital’s trauma service after being involved in a motor vehicle accident as a driver. Preliminary assessmentof his injuries included a basilar skull fracture, multiple facial injuries, and orthopedic injuries. The oral and maxillofacial surgery service was consulted regarding the facial injuries that included displaced right parasymphysis, nondisplaced left ramus, and nondisplaced right subcondylar fractures of the mandible (Figs. 1 and 2). Review of the medical history was positive for Gaucher’s disease type I, diagnosed at age 4. The patient had had a splenectomy at the age of 14 years but had no other relevant medical history. Laboratory values included creatine kinase, 629 U/L; lactate dehydrogenase 426 U/L; aspartate aminotransferase, 93 U/L; and alkaline phosphatase, 118 U/L. The initial complete blood cell count showed a white blood cell count of 24,800 cells/mm3, with the presence of macrocytosis and Howell-Jolly bodies.
Fig. 2, Computed tomographic axial radiograph showing right subcondylar fracture (small auro~] and left ramus fracture (large arrow).
After being cleared for general anesthesia, the patient was taken to the operating room for reduction and stabilization of the mandibular fractures. An intraoral open reduction was performed at the mandibular right parasymphysis together with a closed reduction of the remaining mandibular fractures, with good occlusa! results (Fig. 3). Ten days postoperatively an area of fluctuant swelling was discovered in the mucobuccal fold anterior to the right central and lateral incisors. Severe mobility of these teeth was noted, and they were extracted. Culture reports of the drainage revealed penicillin-resistant Staphylococcus aurezls that respondedto clindamycin, 300 mg every 6 hours. Approximately 14 months after the initial injury the patient was seen for complete dental rehabilitation. A threedimensional computed tomographic scan showed excessive lateral bone formation in the area of the previous mandibuiar fractures (Fig. 4). This excessivelateral bone formation in the symphysis was an esthetic concern of the patient. In the operating room, after 1 million U aqueouspenicillin G intravenously, anterior transosseouswires were removed and the bony symphysis recontoured. A 13 mm endosseous implant was then placed with hydroxyapatite augmentation (Fig. 5). The patient continued taking oral penicillin V 500 mg four times daily for 5 postoperative days, The final restoration of the implant was completed with
Volume 73 Number 1
Gaucher’s disease and mandibular
trauma
25
Fig. 3. Panoramic radiograph showing postoperative results after transosseouswire fixation of parasymphysis and closed reduction of left ramus and right subcondylar fractures.
Fig. 4. Three-dimensional computed tomographic radiograph showing excessivelateral bone formation in area of previously treated mandibular symphysis fracture (arrow).
a fixed splinted denture. At a 2-year follow-up from initial injury the patient was doing well and no mandibular changes were noted on radiographs. DISCIJSSION
Fig. 5. Periapical radiograph showing endosseousimplant in place with hydroxyapatite augmentation.
Fewer than 100 cases of Gaucher’s disease of the maxillofacial region have been reported in the literature.7p lo The fundamental abnormality in the condition is defective activity of the enzyme p-glucosidase and the consequent accumulation of the cerebroside-laden cells in the bone marrow. The resultant clinical features come from the pressure of the expanding abnormal cell mass and the normal vascular supply to the affected bone. The reported cases have revealed some relevant areas of concern for
the treating oral and maxillofacial surgeon. Jaw involvement shows osteoporotic defects interdentally. There have been reported cases of apical resorption of teeth. The affected teeth are usually mobile and if extracted the healing alveolus does not fully recover and does not fill with bone. The foremost concern should be the possibility of hemorrhage. A medical history of epistaxis, hemoptysis, or spontaneous gingival hemorrhage should alert the treating doctor to per-
3RAL ?%JRGQRA-?&D .LPRAipATMoL January 1992
form a detailed medical evaluation preoperatively.” Nonsplenectomized patients with Gaucher’s disease are more prone to prolonged bleeding after any surgical manipulation because of their thrombocytopenia.7,11,l2 This problem can usually be alleviated by splenectomy. In our caseno excessivebleeding was noted during two surgical procedures that included manipulation of a fracture and the extraction of two teeth. An increased incidence of postoperative infection has also been reported in patients with Gaucher’s disease.This has been attributed to the disturbance of the reticuloendothelial system.13However, in only one ‘casewas prophylactic antibiotic therapy prescribed.12 In our casethe postoperative infection was present in the area of a compound mandibular fracture that involved mobile teeth. No conclusion regarding the cause of the infection or the role played by Gaucher’s diseasecan be made. The adult chronic visceral form (type I> of Gaucherls diseasepresents the most challenging diagnostic problem for the physician. Patients with type II die early in infancy, and the patients with type III have clinical signs that prompt a physician’s care. A thorough medical history is the key to recognizing the diseasein older children and adults. The patient may volunteer a history of splenectomy, placement of a femoral head prosthesis, or bone pain. The definitive diagnosis is basedon biopsy of any bony lesion and the measurement of the serum acid phosphataseand glucosyl ceramidase levels. A case of mandibular trauma involving a patient with Gaucher’s diseasetype I is presented. The case
revealed a possible decreasein bone re.modeling not been previously reported as an abnormality of this disease. We thank Dr. J. Hupp for his editorial assistance.
1. Stanbury JB, Wyngarden JB, Fredrickson DS. The metabolic 2. 3. 4. 5. 6.
7.
basis of inherited disease. 3rd ed. New York McGraw-Hill, 1972:738-51. Peters SD, Glew RH, Lee RE. Practical enzymology of the sphingolipidases. New York: Alan R Liss, 1977:72-95. Galjaard H. Genetic metabolic: early diagnosis and prenatal analysis. New York: Elsevier North-Holland, 1980:195-203. Schubiner H, Lefourneau M, Murray DL. Pyogenic osteomyelitis versus pseudo-osteomyelitis in Gaucher’s disease. Clin Pediatr 1987;20:667. Bildman B, Martinez M, Robinson LH. Gaucher’s disease discovered by mandibular biopsy. J Oral Surg 1972;JO:SlO. Lee RE, Robinson DB, Glew RH. Gaucher’s disease: modern enzymatic and anatomic methods of diagnosis. Arch Path01 Lab Med 1981;5:102. Bender IB. Dental observations in Gaucher’s disease. ORAL
SURGORAL MED ORALPATHOL 1959;12:546. 8. Salkv B. Kreel I. Gelernt I. Bauer J. Aufses AH Jr. Solenectomy for Gaucher’s disease. Ann Surg 1979;190:592-4. 9. Groth CG, Collste H, Dreborg S, Hakansson G, Lundgren G, Svennerholm L. Attempt at enzyme replacement in Gaucher disease by renal transplantation. Acta Pediatr Stand 1979;68:475-9. 10. Sela R, Rolliack A, Ulmansky M. Involvement of the mandible in Gaucher’s disease. Br J Oral Surg 1972;9:246. 11. Browne WG. Oral pigmentation and root resorption in Gaucher’s disease. J Oral Surg 1977;35:153. 12. Moth WS. Gaucher’s disease with mandibular bone lesions. ORALSURGORAL MEDORALPATHOL 1953;6:1250. 13. Lau MM, Lichtman DM, Hamati YI, et al. Hip arthroplasty in Gaucher’s disease. J Bone Joint Surg [Am] 1981;63A:598. ,
I
Reprint requests: Glenn R. Regenye, DMD 178 Morris Avenue Springfield, NJ 07081