A c t a Path. Jsp. 26(6): 6292636, 1076
A N AUTOPSY CASE OF TYPE 11 GLYCOGENOSIS
Ichiro ASUKATA*,Shigeo AIZAWA, Mamoru KOSAKAI**, Yuji Kmmo and Eisei ISHIKAWA Department of Pathology, The Jikei Univeraity 8 c h l of Medicine, Tokyo (Received on Feb. 7, 1976)
An autopsy case of Type I1 glycogenosis was reported with detailed description of ultrastructural flndings. In addition to two typical patterns of glycogen deposition, membrane-bound lysosomal glycogen and membranefree cytoplasmic glycogen, we observed numerous vacuolar structures in liver cells and a large deposftion of homogeneous materials between fragmented myocardial fibrils. These flndings were briefly discussed in this manuscript. ACTA PATH. JAP. 26: 629-635, 1976.
Introauctiolz Glycogenosis 'in which the .glycogen concentration in a tissue is increased, is currently divided into 10 types based on enzymatic deficiencies. The rarest in glycogenosis is type 11, also known as Pompe's disease, which is caused by the deficiency of lysosomal acid alpha-1,4-glucosidase and only a few electron microscopic studies have been reported. An autopsy case of type I1 glycogenosis will be described in this manuscript with special emphasis on the ultrastructural changes in the liver and heart. Case Report
1. Clinical history: A twenty-seven day old male baby, normal at birth weighing 2,830 g, was admitted to our Hospital. The chest X-ray showed mild cardiac enlargement. The liver was palpable two finger-breadth below the costal margin. The laboratory examination revealed constant elevation of serum LDH, GOT and ADH levels. Two months later, cardiac enlargement became more remarkable and respiratory distress appeared. The patient died of cardiac failure associated with pneumonia 4 months after birth.
2. Pathology: The autopsy was performed 3 hours after death. He was 62 cm in height and 4 kg in body weight. Small pieces of liver and myocardium were immediately placed in 1.2 per cent glutaraldehyde and postosdcated. Ultrathin %C€E 4%E R &%i /J\%# % @I!@ ZJ11 %# Resent address: *Department of First Internel Medicine, The Jikei University School of Medicine' 3-26-8 Nishi-shinbeshi, Mineto-ku, Tokyo ** Department of Pathology, Teikyo Univeraity School of Medicine, Tokyo. 629
630
Acta Path. Jap.
Fig. 1. The liver cells are distended showing clear vacuolated cytoplasm.
Masson Trichromc,
x 200. Fig. 2. The liver cells contain numerous glycogen granules. Carmine stain, x 200. Fig. 3. The electron micrograph demonstrates numerous membrane-bound lysosomal glycogen and a emall amount of scattered membrane free cytoplasmic glycogen. There are numerous vaouoles (V) with electron translucent homogeneous substances. A Kupffer cell in the sinusoid also contains l p s o m a l glycogen (arrow). x 3,000.
26(5): 1976
I. ASUKATA
631
sections cut from Epon embedded blocks were stained with uranium nitrate and lead acetate for electron microscopic examination.
The liver was enlarged to 210 gm in weight and the cut-surface showed conspicuous swelling with no apparent lobular architecture. With light microscopy, the liver cells were distended compressing the sinusoids except in the central zones. They contained numerous vacuoles in the cytoplasm and small pyknotic nuclei (Fig. 1). The PAS and Best’s carmine stains revealed coarse granular materials filling the vacuoles (Fig. 2). No nuclear glycogen was found. There was neither apparent increase in fibrous elements along the sinusoidal wall, nor enlargement of the Glisson sheaths. The Kupffer cells were not active but occasionally contained PAS positive granules. The most characteristic feature encountered with electron microscope was the membrane-bound glycogen bodies, lysosomal glycogen5, in the liver cells (Figs. 3 and 4). These membrane-bound glycogen bodies, residual glycogen bodies3, measuring up to 8 microns in diameter were so numerous that intracehlar organelles were often displaced. They had no d e h i t e association with any intracellular organelles such as smooth endoplasmic reticulum or mitochondria. There were also glycogen particles occasionally scattered in the cytoplasm free from membrane. The glycogen, whether it was associated with membrane or scattered freely in the cytoplasm, mostly
Fig. 4. A high power view of lysosomal glycogen. There are numerous vacuoles limited by single membrane which are filled with particulated glycogen. x 16,000. ~
632
TYPB II
oLy
A N AUTOPSY CASE OF TYPE 11 GLYCOGENOSIS
Ichiro ASUKATA*,Shigeo AIZAWA, Mamoru KOSAKAI**, Yuji Kmmo and Eisei ISHIKAWA Department of Pathology, The Jikei Univeraity 8 c h l of Medicine, Tokyo (Received on Feb. 7, 1976)
An autopsy case of Type I1 glycogenosis was reported with detailed description of ultrastructural flndings. In addition to two typical patterns of glycogen deposition, membrane-bound lysosomal glycogen and membranefree cytoplasmic glycogen, we observed numerous vacuolar structures in liver cells and a large deposftion of homogeneous materials between fragmented myocardial fibrils. These flndings were briefly discussed in this manuscript. ACTA PATH. JAP. 26: 629-635, 1976.
Introauctiolz Glycogenosis 'in which the .glycogen concentration in a tissue is increased, is currently divided into 10 types based on enzymatic deficiencies. The rarest in glycogenosis is type 11, also known as Pompe's disease, which is caused by the deficiency of lysosomal acid alpha-1,4-glucosidase and only a few electron microscopic studies have been reported. An autopsy case of type I1 glycogenosis will be described in this manuscript with special emphasis on the ultrastructural changes in the liver and heart. Case Report
1. Clinical history: A twenty-seven day old male baby, normal at birth weighing 2,830 g, was admitted to our Hospital. The chest X-ray showed mild cardiac enlargement. The liver was palpable two finger-breadth below the costal margin. The laboratory examination revealed constant elevation of serum LDH, GOT and ADH levels. Two months later, cardiac enlargement became more remarkable and respiratory distress appeared. The patient died of cardiac failure associated with pneumonia 4 months after birth.
2. Pathology: The autopsy was performed 3 hours after death. He was 62 cm in height and 4 kg in body weight. Small pieces of liver and myocardium were immediately placed in 1.2 per cent glutaraldehyde and postosdcated. Ultrathin %C€E 4%E R &%i /J\%# % @I!@ ZJ11 %# Resent address: *Department of First Internel Medicine, The Jikei University School of Medicine' 3-26-8 Nishi-shinbeshi, Mineto-ku, Tokyo ** Department of Pathology, Teikyo Univeraity School of Medicine, Tokyo. 629
630
Acta Path. Jap.
Fig. 1. The liver cells are distended showing clear vacuolated cytoplasm.
Masson Trichromc,
x 200. Fig. 2. The liver cells contain numerous glycogen granules. Carmine stain, x 200. Fig. 3. The electron micrograph demonstrates numerous membrane-bound lysosomal glycogen and a emall amount of scattered membrane free cytoplasmic glycogen. There are numerous vaouoles (V) with electron translucent homogeneous substances. A Kupffer cell in the sinusoid also contains l p s o m a l glycogen (arrow). x 3,000.
26(5): 1976
I. ASUKATA
631
sections cut from Epon embedded blocks were stained with uranium nitrate and lead acetate for electron microscopic examination.
The liver was enlarged to 210 gm in weight and the cut-surface showed conspicuous swelling with no apparent lobular architecture. With light microscopy, the liver cells were distended compressing the sinusoids except in the central zones. They contained numerous vacuoles in the cytoplasm and small pyknotic nuclei (Fig. 1). The PAS and Best’s carmine stains revealed coarse granular materials filling the vacuoles (Fig. 2). No nuclear glycogen was found. There was neither apparent increase in fibrous elements along the sinusoidal wall, nor enlargement of the Glisson sheaths. The Kupffer cells were not active but occasionally contained PAS positive granules. The most characteristic feature encountered with electron microscope was the membrane-bound glycogen bodies, lysosomal glycogen5, in the liver cells (Figs. 3 and 4). These membrane-bound glycogen bodies, residual glycogen bodies3, measuring up to 8 microns in diameter were so numerous that intracehlar organelles were often displaced. They had no d e h i t e association with any intracellular organelles such as smooth endoplasmic reticulum or mitochondria. There were also glycogen particles occasionally scattered in the cytoplasm free from membrane. The glycogen, whether it was associated with membrane or scattered freely in the cytoplasm, mostly
Fig. 4. A high power view of lysosomal glycogen. There are numerous vacuoles limited by single membrane which are filled with particulated glycogen. x 16,000. ~
632
TYPB II
oLy
![[Plasma cell inclusions in Pompe's disease (glycogenosis type II). Second case of a new anomaly].](/assets/img/hold.png)
