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Hydrocephalus associated with glycogen storage disease type II (pompe’s disease)
Hydrocephalus Associated With Glycogen Storage Disease Type II (Pompe’s Disease) Mustafa Sahin, MD, PhD and Adre J. du Plessis, MBChB, MPH The authors describe a case of hydrocephalus in an 8-month, 2-week-old infant who had been previously diagnosed with glycogen storage disease type II. Cranial imaging revealed no evidence of obstruction within the ventricular system. This case adds to the central nervous system complications associated with this disorder. Several possible mechanisms for the hydrocephalus observed in this infant are discussed. © 1999 by Elsevier Science Inc. All rights reserved. Sahin M, duPlessis AJ. Hydrocephalus associated with glycogen storage disease type II (Pompe’s disease). Pediatr Neurol 1999;21:674-676.
Introduction Glycogen storage disease type II (GSD II) is an autosomal-recessive disease resulting from a defect in alpha1,4-glucosidase (acid maltase). The disorder manifests in infantile-, juvenile-, and adult-onset forms, depending on the degree of insufficiency of this enzyme [1]. The infantile form typically presents with cardiomyopathy, hypotonia, and weakness. Macroglossia and hepatomegaly are common accompaniments. Electromyography reveals fibrillations and pseudomyotonic discharges [2,3]. The disease progresses rapidly, with increasing generalized weakness, including involvement of the bulbar musculature, because of diffuse glycogen accumulation within the central nervous system and muscles. Death results from
From the Department of Neurology; Children’s Hospital and Harvard Medical School; Boston, Massachusetts.
674
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cardiorespiratory failure within the first year of life. In contrast the juvenile and adult forms of GSD II predominantly affect the skeletal muscles, with the intracranial pathologic features confined to the cerebral vasculature and possibly manifesting as a diffuse arteriopathy and fusiform aneurysms, especially involving the basilar artery [4,5]. Pathologic studies of infantile-onset GSD II have demonstrated involvement of all organs. The skeletal muscles, the heart, and the liver have marked accumulation of glycogen in the lysosomes and cytoplasm. Glycogen is also deposited in the kidneys, lymphocytes, eyes, skin, and smooth muscles. Within the central nervous system, glycogen accumulation is most striking in the anterior horn cells of the spinal cord and motor nuclei of the brainstem [2], with the cerebral cortical neurons the least involved [6]. Among the non-neuronal cells, glycogen storage is prominent in the astrocytes in the cerebral cortex, subcortical white matter, and cerebellum [2,7,8]. Endothelial cells throughout the brain, including in the capillaries of the choroid plexus, may be enlarged with glycogen [6]. Oligodendrocytes and Schwann cells also contain glycogen deposition [9]. Despite these demonstrations of diffuse pathologic findings in the nervous system of patients with infantile-onset GSD II, there have been no reports of hydrocephalus associated with this disease.
Case Report The patient was an 8-month, 2-week-old male born at term to a 31-year-old mother (gravida 3, para 1-2), with one previous spontaneous abortion. The pregnancy was complicated by mild maternal hypertension, a urinary tract infection, and oligohydramnios. The infant was delivered vaginally and cried immediately. Birth weight was 3.9 kg. The neonatal period was uneventful. At 4 months of age the infant became diaphoretic and developed respiratory distress. A chest radiograph revealed massive cardiomegaly. An electrocardiogram (EKG) revealed a short PR interval and biventricular hypertrophy. The infant was admitted to the hospital in cardiac failure caused by hypertrophic cardiomyopathy. Serum creatine kinase was 899 U/L (normal 4-175 U/L). Electron microscopic studies of an endomyocardial biopsy revealed lysosomal deposition of glycogen, consistent with GSD II. The diagnosis was confirmed by the finding of fibroblast acid maltase activity of zero units. The patient was treated as an outpatient with lasix, digoxin, captopril, carnitine, potassium-chloride supplements, and a high-protein diet. He was readmitted to the hospital at 6 months, 2 weeks of age for respiratory distress. Critical respiratory status and episodes of desaturation and bradycardia complicated his hospital stay. An echocardiogram at 8
Communications should be addressed to: Dr. Sahin; Department of Neurology; Children’s Hospital; 300 Longwood Avenue, Fegan 11; Boston, MA 02115. Received February 23, 1999; accepted May 26, 1999.
© 1999 by Elsevier Science Inc. All rights reserved. PII S0887-8994(99)00064-8 ● 0887-8994/99/$20.00
Figure 1. Horizontal plane of the cranial CT scan reveals dilatation of the prepontine, peripontine, and suprasellar cisterns (A), as well as severe dilatation of the lateral, third, and fourth ventricles (B). There is extensive white matter low attenuation, predominently in the frontal periventricular area (B).
months of age revealed severe left ventricular hypertrophy and hyperdynamic left ventricular function with a normal shortening fraction. At 8 months, 2 weeks of age, he was observed to have a bulging anterior fontanel. Developmentally, he smiled at 3 weeks, fixed and followed at 6 weeks, and began vocalizing at 6-8 weeks. He could not roll over. He was able to lift his legs from the bed and turn his head from side to side. At the time of diagnosis of GSD II, his neurologic examination revealed generalized hypotonia, with poor head control and decreased deep tendon reflexes. On the initial examination, his weight was less than the fifth percentile. His head circumference was 47 cm (ninetieth percentile), which had increased from 43 cm (twenty-fifth percentile) during a period of 8 weeks. The anterior fontanel was open and tense, and the scalp veins were conspicuous. He had prominent forehead, down-slanting palpebral fissures, and low-set, posteriorly rotated ears. A tracheotomy was in place. The cardiac examination revealed a systolic murmur. The liver edge was firm and enlarged to 5 cm below the right costal margin, but splenomegaly was not evident. The infant was alert and attentive. He fixed and followed visually. His pupils were equal, round, and reactive to light, and extraocular movements were intact. He had a mild facial diplegia. The tongue protruded in the midline but was not enlarged and demonstrated no fasciculations. The motor examination revealed profound hypotonia and weakness throughout, with no spontaneous movements. There were no fasciculations. The extremity muscles were hypertrophic and firm. Deep tendon reflexes were absent. Plantar responses were flexor bilaterally. The infant grimaced to pinprick in all four extremities. Cranial computed tomography (CT) revealed severe hydrocephalus with dilatation of the lateral, third, and fourth ventricles (Fig 1). The prepontine, peripontine, and suprasellar cisterns were also dilated. There was extensive white matter low attenuation, predominantly in periventricular regions, consistent with transependymal interstitial edema. No evidence of posterior fossa or cervicomedullary junction mass or of aqueductal stenosis was observed. Magnetic resonance imaging could not be obtained because of an indwelling ferromagnetic tracheotomy tube. The infant underwent placement of a ventriculoperitoneal shunt. Cerebrospinal fluid (CSF) obtained in the operating room contained 1 leukocyte, 40 erythrocytes, protein 7.9 mg/dL, and glucose 59 mg/dL. Bacterial cultures remained sterile. Follow-up CT scan after the ventriculoperitoneal shunt placement revealed a mild decrease in ventricular size and a marked decrease in transependymal edema. There was a paucity of white matter and prominent extra-axial fluid.
Discussion To the authors’ knowledge, this report is the first of a case of hydrocephalus associated with GSD II. The authors’ patient presented at 4 months of age with cardiomyopathy, hypotonia, weakness, and hepatomegaly and developed hydrocephalus at 8 months. The mechanism for the hydrocephalus in this infant is unclear but probably relates to the GSD II. Hydrocephalus may result from oversecretion, obstruction, or impaired absorption of CSF. The vast majority of CSF originates from the choroid plexuses located in the lateral ventricles. Oversecretion of CSF by choroid plexus carcinoma or papilloma can lead to hydrocephalus. However, the cranial CT scan revealed no evidence of such a tumor. Therefore the hydrocephalus in this case was the result of obstruction of CSF flow or absorption. Because the authors’ patient had enlargement of all four ventricles on the CT scan, the obstruction must have been beyond the fourth ventricle. CSF leaves the fourth ventricle by way of the foramina of Luschka and Magendie and drains into the posterior fossa and basal cisterns. The patency of the basal cisterns in the authors’ patient made obstruction at this level unlikely. From the cisterns, most of the CSF is directed over the hemispheres toward the superior sagittal sinus, where it is absorbed into the blood through the arachnoid villi. The most likely site of obstruction in the authors’ patient was at the level of the arachnoid villi. Several possible mechanisms can account for decreased CSF absorption at the arachnoid villi. The absorption depends on the gradient between the CSF pressure and venous blood pressure. Thus, venous hypertension can result in decreased absorption. The most common reasons for increased venous pressure are right ventricular failure, superior vena cava syndrome, venous sinus thrombosis, and the presence of high-flow arteriovenous malformations. The clinical and diagnostic findings in this infant
Sahin and duPlessis: Hydrocephalus with GSD II 675
argue against these possible mechanisms. First, four serial echocardiograms, performed on this patient between 6 and 9 months of age, revealed no evidence of right ventricular dysfunction or enlargement of the right atrium, making increased right ventricular pressure unlikely. Second, cranial imaging revealed no evidence of venous sinus thrombosis. In addition the patient had no clinical evidence of superior vena cava syndrome or arteriovenous malformations. An alternative mechanism for obstruction at the level of the arachnoid villi is mechanical blockage at the level of the subarachnoid space. Leptomeningeal storage of mucopolysaccharides is the proposed mechanism for hydrocephalus commonly observed in Hurler’s and Hunter’s syndromes [10]. Placement of an isotope into the lumbar space of a patient with Hunter’s syndrome resulted in detection of the isotope in the lateral ventricles but not over the surface of the hemispheres. This finding suggests that hydrocephalus in mucopolysaccaridoses is caused by obstruction at the level of the meninges or arachnoid villi. Although such a test was not performed in the authors’ patient, the cranial CT findings were similar to those observed in patients with Hunter’s and Hurler’s syndromes. Although the anatomic characteristics of the arachnoid villi in GSD II have not been reported to date, similar structures (i.e., placental chorionic villi) are known to accumulate glycogen in GSD II [11]. Furthermore, neuropathologic studies on GSD II have revealed marked glycogen storage in astrocytes, which may in turn hinder CSF absorption into the capillaries, which are surrounded by astrocytic endfeet [12]. Taken together, these data raise the possibility that glycogen deposition in pericapillary astrocytes or arachnoid villi, or both, may interfere with CSF absorption in patients with GSD II. Confirmation of this proposed mechanism for hydrocephalus in GSDII awaits further pathologic studies. Advances in cardiac, respiratory, and nutritional support have prolonged the survival of children with the infantile form of GSD II. The importance of this improved longevity is highlighted by the promise of future genetic interventions for this condition. Of similar importance will be the timely diagnosis and intervention of reversible com-
676
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Vol. 21 No. 3
plications that may further compromise the neurologic outcome. The case reported here illustrates one such complication not previously described, the development of hydrocephalus. The authors recommend that hydrocephalus be excluded in children with GSD II in whom there is accelerated head growth and neurologic deterioration. The authors thank Dr. Joseph J. Volpe for critical review of this manuscript.
References [1] Hirschhorn R. Glycogen storage disease type II: Acid alphaglucosidase (acid maltase) deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill, 1995:2443-64. [2] Hogan GR, Gutmann L, Schmidt R, Gilbert E. Pompe’s disease. Neurology 1969;19:894-900. [3] Bordiuk JM, Legato MJ, Lovelace RE, Blumenthal S. Pompe’s disease— electromyographic, elecron microscopic and cardiovascular aspects. Arch Neurol 1970;23:113-9. [4] Makos MM, McComb RD, Hart MN, Bennett DR. Alphaglucosidase deficiency and basilar artery aneurysm: Report of a sibship. Ann Neurol 1987;22:629-33. [5] Braunsdorf WE. Fusiform aneurysm of basilar artery and ectatic internal carotid arteries associated with glycogenosis type 2 (Pompe’s disease). Neurosurgery 1987;21:748-9. [6] Dincsoy MY, Dincsoy HP, Kessler AD, Jackson MA, Sidbury JB. Generalized glycogenosis and associated endocardial fibroelastosis. J Pediatr 1965;67:728-40. [7] Kahana D, Telem C, Steinitz K, Solomon M. Generalized glycogenosis, report of a case with deficiency of alpha glucosidase. J Pediatr 1964;65:243-51. [8] Lake BD. Lysosomal and perixosomal disorders. In: Adams JH, Duchen LW, eds. Greenfield’s neuropathology, 5th ed. New York: Oxford University Press, 1992:768-71. [9] Araoz C, Sun CN, Shenefelt R, White HJ. Glycogenosis type II (Pompe’s disease): Ultrastructure of peripheral nerves. Neurology 1974; 24:739-42. [10] Watts RWE, Spellacy E, Kendall BE, duBoulay G, Gibbs DA. Computed tomography studies on patients with mucopolysaccaridoses. Neuroradiology 1981;21:9-23. [11] Hug G, Chuck G, Chen Y-T, Kay HH, Bossen EH. Chorionic villus ultrastructure in type II glycogen storage disease (Pompe’s disease). N Engl J Med 1991;324:342-3. [12] Friede RL. Diseases of carbohydrate metabolism. In: Developmental neuropathology, 2nd ed. New York: Springer-Verlag, 1989:40624.
Introduction Glycogen storage disease type II (GSD II) is an autosomal-recessive disease resulting from a defect in alpha1,4-glucosidase (acid maltase). The disorder manifests in infantile-, juvenile-, and adult-onset forms, depending on the degree of insufficiency of this enzyme [1]. The infantile form typically presents with cardiomyopathy, hypotonia, and weakness. Macroglossia and hepatomegaly are common accompaniments. Electromyography reveals fibrillations and pseudomyotonic discharges [2,3]. The disease progresses rapidly, with increasing generalized weakness, including involvement of the bulbar musculature, because of diffuse glycogen accumulation within the central nervous system and muscles. Death results from
From the Department of Neurology; Children’s Hospital and Harvard Medical School; Boston, Massachusetts.
674
PEDIATRIC NEUROLOGY
Vol. 21 No. 3
cardiorespiratory failure within the first year of life. In contrast the juvenile and adult forms of GSD II predominantly affect the skeletal muscles, with the intracranial pathologic features confined to the cerebral vasculature and possibly manifesting as a diffuse arteriopathy and fusiform aneurysms, especially involving the basilar artery [4,5]. Pathologic studies of infantile-onset GSD II have demonstrated involvement of all organs. The skeletal muscles, the heart, and the liver have marked accumulation of glycogen in the lysosomes and cytoplasm. Glycogen is also deposited in the kidneys, lymphocytes, eyes, skin, and smooth muscles. Within the central nervous system, glycogen accumulation is most striking in the anterior horn cells of the spinal cord and motor nuclei of the brainstem [2], with the cerebral cortical neurons the least involved [6]. Among the non-neuronal cells, glycogen storage is prominent in the astrocytes in the cerebral cortex, subcortical white matter, and cerebellum [2,7,8]. Endothelial cells throughout the brain, including in the capillaries of the choroid plexus, may be enlarged with glycogen [6]. Oligodendrocytes and Schwann cells also contain glycogen deposition [9]. Despite these demonstrations of diffuse pathologic findings in the nervous system of patients with infantile-onset GSD II, there have been no reports of hydrocephalus associated with this disease.
Case Report The patient was an 8-month, 2-week-old male born at term to a 31-year-old mother (gravida 3, para 1-2), with one previous spontaneous abortion. The pregnancy was complicated by mild maternal hypertension, a urinary tract infection, and oligohydramnios. The infant was delivered vaginally and cried immediately. Birth weight was 3.9 kg. The neonatal period was uneventful. At 4 months of age the infant became diaphoretic and developed respiratory distress. A chest radiograph revealed massive cardiomegaly. An electrocardiogram (EKG) revealed a short PR interval and biventricular hypertrophy. The infant was admitted to the hospital in cardiac failure caused by hypertrophic cardiomyopathy. Serum creatine kinase was 899 U/L (normal 4-175 U/L). Electron microscopic studies of an endomyocardial biopsy revealed lysosomal deposition of glycogen, consistent with GSD II. The diagnosis was confirmed by the finding of fibroblast acid maltase activity of zero units. The patient was treated as an outpatient with lasix, digoxin, captopril, carnitine, potassium-chloride supplements, and a high-protein diet. He was readmitted to the hospital at 6 months, 2 weeks of age for respiratory distress. Critical respiratory status and episodes of desaturation and bradycardia complicated his hospital stay. An echocardiogram at 8
Communications should be addressed to: Dr. Sahin; Department of Neurology; Children’s Hospital; 300 Longwood Avenue, Fegan 11; Boston, MA 02115. Received February 23, 1999; accepted May 26, 1999.
© 1999 by Elsevier Science Inc. All rights reserved. PII S0887-8994(99)00064-8 ● 0887-8994/99/$20.00
Figure 1. Horizontal plane of the cranial CT scan reveals dilatation of the prepontine, peripontine, and suprasellar cisterns (A), as well as severe dilatation of the lateral, third, and fourth ventricles (B). There is extensive white matter low attenuation, predominently in the frontal periventricular area (B).
months of age revealed severe left ventricular hypertrophy and hyperdynamic left ventricular function with a normal shortening fraction. At 8 months, 2 weeks of age, he was observed to have a bulging anterior fontanel. Developmentally, he smiled at 3 weeks, fixed and followed at 6 weeks, and began vocalizing at 6-8 weeks. He could not roll over. He was able to lift his legs from the bed and turn his head from side to side. At the time of diagnosis of GSD II, his neurologic examination revealed generalized hypotonia, with poor head control and decreased deep tendon reflexes. On the initial examination, his weight was less than the fifth percentile. His head circumference was 47 cm (ninetieth percentile), which had increased from 43 cm (twenty-fifth percentile) during a period of 8 weeks. The anterior fontanel was open and tense, and the scalp veins were conspicuous. He had prominent forehead, down-slanting palpebral fissures, and low-set, posteriorly rotated ears. A tracheotomy was in place. The cardiac examination revealed a systolic murmur. The liver edge was firm and enlarged to 5 cm below the right costal margin, but splenomegaly was not evident. The infant was alert and attentive. He fixed and followed visually. His pupils were equal, round, and reactive to light, and extraocular movements were intact. He had a mild facial diplegia. The tongue protruded in the midline but was not enlarged and demonstrated no fasciculations. The motor examination revealed profound hypotonia and weakness throughout, with no spontaneous movements. There were no fasciculations. The extremity muscles were hypertrophic and firm. Deep tendon reflexes were absent. Plantar responses were flexor bilaterally. The infant grimaced to pinprick in all four extremities. Cranial computed tomography (CT) revealed severe hydrocephalus with dilatation of the lateral, third, and fourth ventricles (Fig 1). The prepontine, peripontine, and suprasellar cisterns were also dilated. There was extensive white matter low attenuation, predominantly in periventricular regions, consistent with transependymal interstitial edema. No evidence of posterior fossa or cervicomedullary junction mass or of aqueductal stenosis was observed. Magnetic resonance imaging could not be obtained because of an indwelling ferromagnetic tracheotomy tube. The infant underwent placement of a ventriculoperitoneal shunt. Cerebrospinal fluid (CSF) obtained in the operating room contained 1 leukocyte, 40 erythrocytes, protein 7.9 mg/dL, and glucose 59 mg/dL. Bacterial cultures remained sterile. Follow-up CT scan after the ventriculoperitoneal shunt placement revealed a mild decrease in ventricular size and a marked decrease in transependymal edema. There was a paucity of white matter and prominent extra-axial fluid.
Discussion To the authors’ knowledge, this report is the first of a case of hydrocephalus associated with GSD II. The authors’ patient presented at 4 months of age with cardiomyopathy, hypotonia, weakness, and hepatomegaly and developed hydrocephalus at 8 months. The mechanism for the hydrocephalus in this infant is unclear but probably relates to the GSD II. Hydrocephalus may result from oversecretion, obstruction, or impaired absorption of CSF. The vast majority of CSF originates from the choroid plexuses located in the lateral ventricles. Oversecretion of CSF by choroid plexus carcinoma or papilloma can lead to hydrocephalus. However, the cranial CT scan revealed no evidence of such a tumor. Therefore the hydrocephalus in this case was the result of obstruction of CSF flow or absorption. Because the authors’ patient had enlargement of all four ventricles on the CT scan, the obstruction must have been beyond the fourth ventricle. CSF leaves the fourth ventricle by way of the foramina of Luschka and Magendie and drains into the posterior fossa and basal cisterns. The patency of the basal cisterns in the authors’ patient made obstruction at this level unlikely. From the cisterns, most of the CSF is directed over the hemispheres toward the superior sagittal sinus, where it is absorbed into the blood through the arachnoid villi. The most likely site of obstruction in the authors’ patient was at the level of the arachnoid villi. Several possible mechanisms can account for decreased CSF absorption at the arachnoid villi. The absorption depends on the gradient between the CSF pressure and venous blood pressure. Thus, venous hypertension can result in decreased absorption. The most common reasons for increased venous pressure are right ventricular failure, superior vena cava syndrome, venous sinus thrombosis, and the presence of high-flow arteriovenous malformations. The clinical and diagnostic findings in this infant
Sahin and duPlessis: Hydrocephalus with GSD II 675
argue against these possible mechanisms. First, four serial echocardiograms, performed on this patient between 6 and 9 months of age, revealed no evidence of right ventricular dysfunction or enlargement of the right atrium, making increased right ventricular pressure unlikely. Second, cranial imaging revealed no evidence of venous sinus thrombosis. In addition the patient had no clinical evidence of superior vena cava syndrome or arteriovenous malformations. An alternative mechanism for obstruction at the level of the arachnoid villi is mechanical blockage at the level of the subarachnoid space. Leptomeningeal storage of mucopolysaccharides is the proposed mechanism for hydrocephalus commonly observed in Hurler’s and Hunter’s syndromes [10]. Placement of an isotope into the lumbar space of a patient with Hunter’s syndrome resulted in detection of the isotope in the lateral ventricles but not over the surface of the hemispheres. This finding suggests that hydrocephalus in mucopolysaccaridoses is caused by obstruction at the level of the meninges or arachnoid villi. Although such a test was not performed in the authors’ patient, the cranial CT findings were similar to those observed in patients with Hunter’s and Hurler’s syndromes. Although the anatomic characteristics of the arachnoid villi in GSD II have not been reported to date, similar structures (i.e., placental chorionic villi) are known to accumulate glycogen in GSD II [11]. Furthermore, neuropathologic studies on GSD II have revealed marked glycogen storage in astrocytes, which may in turn hinder CSF absorption into the capillaries, which are surrounded by astrocytic endfeet [12]. Taken together, these data raise the possibility that glycogen deposition in pericapillary astrocytes or arachnoid villi, or both, may interfere with CSF absorption in patients with GSD II. Confirmation of this proposed mechanism for hydrocephalus in GSDII awaits further pathologic studies. Advances in cardiac, respiratory, and nutritional support have prolonged the survival of children with the infantile form of GSD II. The importance of this improved longevity is highlighted by the promise of future genetic interventions for this condition. Of similar importance will be the timely diagnosis and intervention of reversible com-
676
PEDIATRIC NEUROLOGY
Vol. 21 No. 3
plications that may further compromise the neurologic outcome. The case reported here illustrates one such complication not previously described, the development of hydrocephalus. The authors recommend that hydrocephalus be excluded in children with GSD II in whom there is accelerated head growth and neurologic deterioration. The authors thank Dr. Joseph J. Volpe for critical review of this manuscript.
References [1] Hirschhorn R. Glycogen storage disease type II: Acid alphaglucosidase (acid maltase) deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill, 1995:2443-64. [2] Hogan GR, Gutmann L, Schmidt R, Gilbert E. Pompe’s disease. Neurology 1969;19:894-900. [3] Bordiuk JM, Legato MJ, Lovelace RE, Blumenthal S. Pompe’s disease— electromyographic, elecron microscopic and cardiovascular aspects. Arch Neurol 1970;23:113-9. [4] Makos MM, McComb RD, Hart MN, Bennett DR. Alphaglucosidase deficiency and basilar artery aneurysm: Report of a sibship. Ann Neurol 1987;22:629-33. [5] Braunsdorf WE. Fusiform aneurysm of basilar artery and ectatic internal carotid arteries associated with glycogenosis type 2 (Pompe’s disease). Neurosurgery 1987;21:748-9. [6] Dincsoy MY, Dincsoy HP, Kessler AD, Jackson MA, Sidbury JB. Generalized glycogenosis and associated endocardial fibroelastosis. J Pediatr 1965;67:728-40. [7] Kahana D, Telem C, Steinitz K, Solomon M. Generalized glycogenosis, report of a case with deficiency of alpha glucosidase. J Pediatr 1964;65:243-51. [8] Lake BD. Lysosomal and perixosomal disorders. In: Adams JH, Duchen LW, eds. Greenfield’s neuropathology, 5th ed. New York: Oxford University Press, 1992:768-71. [9] Araoz C, Sun CN, Shenefelt R, White HJ. Glycogenosis type II (Pompe’s disease): Ultrastructure of peripheral nerves. Neurology 1974; 24:739-42. [10] Watts RWE, Spellacy E, Kendall BE, duBoulay G, Gibbs DA. Computed tomography studies on patients with mucopolysaccaridoses. Neuroradiology 1981;21:9-23. [11] Hug G, Chuck G, Chen Y-T, Kay HH, Bossen EH. Chorionic villus ultrastructure in type II glycogen storage disease (Pompe’s disease). N Engl J Med 1991;324:342-3. [12] Friede RL. Diseases of carbohydrate metabolism. In: Developmental neuropathology, 2nd ed. New York: Springer-Verlag, 1989:40624.