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Congenital fiber type disproportion myopathy in Lowe syndrome
Congenital Fiber Type Disproportion Myopathy in Lowe Syndrome Jun Kohyama, M D * , F u m i o Niimura, MD*, Koichiro Kawashima, MDt, Yoshihide Iwakawa, MD*, and Ikuya Nonaka, MD§
Two brothers with the typical clinical features of oculocerebro-renal syndrome of Lowe exhibited delays in developmental milestones, muscular weakness and hypotonia, and high serum creatine kinase activity. The biopsied muscle revealed selective type 1 fiber atrophy and mild type 1 fiber predominance, similar to that observed in congenital fiber type disproportion myopathy. The abnormal fiber type distribution may be responsible for the common finding of muscle hypotonia in this syndrome.
motor development was delayed. He experienced a febrile tonic seizure at 9 months of age. He learned to walk at 3 years of age. On examination at 4 years, 9 months of age, he spoke only a few meaningful words. He was small in height (S.D. -2.4); however, no external anomaly was observed. He was hyperkinetic and had stereotypic hand movements. He stood up from the floor with mild Gowers' maneuver; he placed his hands on the floor and then lifted his hips and stood up. The facial and neck muscles were spared. No waddling gait, apparent muscle atrophy, or ataxia was observed. He had generalized muscle hypotonia. Deep tendon reflexes were absent and no pathologic reflexes could be elicited. Because of nystagmus in all directions, his eye positioning was unsteady, but ocular movement was not limited. Electroencephalography (EEG) revealed mild epileptic abnormalities, while cranial computed tomography (CT) was unremarkable. Except for an elevated serum CK level of 322 U/L (normal: < 60 U/L), blood chemistry results were within normal limits. Low molecular weight proteinuria, uricosuria, aminoaciduria, and calciuria were detected. Tubular reabsorption of phosphate (%TRP) was decreased (Table 1). Motor nerve conduction velocity was normal. Patient 2. The younger brother was born at term after a normal pregnancy, weighing 3,120 gm. He had congenital cataracts which were also removed by aspiration. He was a floppy infant with delayed motor Table 1.
Renal tubular functions in the patients
Patient 1
Patient 2
Normal Range
277 mg/dl
256 mg/dl
< 150 mg/dl
80,000 ~tg/L
88,000 ~tg/L
< 250 ~tg/L
196 ~tg/ml
152 lag/ml
0
Calcium/creatinine
0.58
1.16
< 0.20
Fractional excretion of uric acid
19.1%
23.7%
< 15.0%
Protein in urine Urinary fl2 microglobulin
Kohyama J, Niimura F, Kawashima K, Iwakawa Y, Nonaka I. Congenital fiber type disproportion myopathy in Lowe syndrome. Pediatr Neurol 1989;5:373-6.
Introduction The oculo-cerebro-renal syndrome (OCRS) of Lowe is characterized clinically by mental retardation, eye changes (i.e., glaucoma, congenital cataracts), and renal impairment [1]. Although the additional findings of muscle hypotonia and absence of deep tendon reflexes suggest probable muscle involvement, previous histologic muscle examinations have been inconclusive [2-5]. Because of elevated creatine kinase (CK) levels in 2 brothers with OCRS, muscle was biopsied and examined histologically.
Case Reports We report 2 brothers with nonconsanguineous, healthy parents. No neuromuscular or retinal disorders were observed in other family members. Patient 1. The elder brother was born at term after a normal pregnancy, weighing 2,970 gm. He had congenital cataracts which were removed by bilateral aspiration. He was a floppy infant and his psycho-
From the *Department of Pediatrics; Tsuchiura Kyoudou Hospital; Ibaraki, Japan; tlnstitute of Special Education; Tsukuba University; Tsububa, Japan; *Department of Pediatrics; Faculty of Medicine; Tokyo Medical and Dental University; Tokyo, Japan; and §Division of Ultrastructural Research; National Institute of Neuroscience; Kodaira, Japan.
Lysozyme
Percentage of tubular reabsorption of amino acids: Glycine
74.4
68.3
92.9 - 99.0
Valine
99.1
99.5
99.7 - 99.9
99.1
98.3 - 99.7
Methionine
100
Isoleucine
99.3
99.5
99.2 - 99.9
Leucine
99.3
99.2
99.6 - 99.9
Tyrosine
97.2
96.2
98.2 - 99.3
Phenylalanine
98.7
97.7
98.8 - 99.7
Histidine
81.1
72.6
90.3 - 98.4
Lysine
95.5
94.0
98.5 - 99.8
99.3
99.0 - 99.9
Arginine Percentage of tubular reabsorption of phosphate
100 84
50
89 - 98
Communications should be addressed to: Dr. Kohyama; Department of Pediatrics; Tsuchiura Kyoudou Hospital; Manabe-Shinmachi 11-7; Tsuchiura, Ibaraki 300, Japan. Received August 15, 1989; accepted September 21, 1989.
Kohyama et al: Lowe Syndrome
373
Figure I. (A) Muscle biopsy J}'om Patient 2: ATPase stain with preincubation at pH 4.6. Although type 1 (1). 2A (A), and 2B (B) fibers are distributed in a mosaic pattern, type I fibers are selective[y atrophic'. Original magnification, x60. (B) Muscle biopsy from Patient 1." NADH-TR stain. Small type I fibers have a core-like. moth-eaten appearanee (arrow). Original magnification, x120. milestones. He experienced a febrile tonic seizure at 1 year, 6 months of age. During the most recent clinical examination at 3 years, 4 months of age, he was small in height (S.D. -3.7) and could stand only with support because of mild muscle weakness. He spoke only a few meaningful words. His physical and neurologic condition was similar to that of his brother. He was mentally retarded and had nystagmus and decreased muscle tone with hypoactive tendon reflexes. Laboratory examination also demonstrated similar results, including an elevated CK level of 186 U/L, low molecular weight proteinuria, uricosuria, aminoaciduria, calciuria, and remarkably decreased %TRP (Table 1). EEG demonstrated an epileptic abnormality, while cranial CT was unremarkable. Muscle Pathology. Specimens were obtained from their biceps brachii muscles. Serial frozen sections were stained with hematoxylin and eosin, and by various histochemical methods, including NADHtetrazolium rednctase (NADH-TR), modified Gomori trichrome, oil red O, periodic acid Schiff (PAS), acid phosphatase, alkaline phosphatase, cytochrome c oxidase, and myosin adenosine triphosphatase (ATPase) with alkaline and acid preincubation.
374
PEDIATRIC NEUROLOGY
Vol. 5 No. 6
In both patients, the muscle disclosed no fiber necrosis or increased connective or adipose tissue. On ATPase staining (Fig 1A), type 1, 2A, and 2B fibers were distributed in a normal mosaic pattern, while type 1 fibers were more than 12% smaller in diameter than normal type 2 fibers (Fig 2) [6]. No fiber type deficiency or increase in type 2C fibers was observed. Type 1 fibers were predominant (60% vs normal: < 55% [6]) in Patient 2. Variability coefficients were less than 250 in both specimens [7]. On NADH-TR staining of the muscle of Patient 1, scattered fibers were observed with disorganized intermyofibrillar networks and a multiple core-like or moth-eaten appearance (Fig 1B). Modified Gomori trichrome staining revealed no ragged-red fibers or nemaline bodies. There was no excess accumulation of PAS or oil,red-O positive material.
Discussion The clinical features of our patients, including mental retardation,
ocular
abnormalities,
renal manifestations,
a n d n e u r a l i n v o l v e m e n t , all w e r e c h a r a c t e r i s t i c o f O C R S
MuscleFiberType A
MeanDiameter(pm) centageof Fibers
i_
2C []
I
2B 2A X O 25.9 22.4 20'4 50% 22.6% 27%
19.7 0.4%
LL 50. O f,_
Q)
.O E
/
Z
,o
/ ....-~..._~.
i x-
/
/
10
15
•%-'-., 20
25
30
35
40
Diameter (pm)
MuscleFiberType
1
i
~ •
100" U3 L
Q)
..O LL o
.w
f,-
Q)
..O 50" E
MeanDiameter(pro) ~ c e n t a g e of Fibers
2A
2B
2C
©
x
[]
17.7 18.3 21.3 9.9 60%
10%
29%
1%
Z
0 5
10
15
2'0
2's
3'o
Diameter (pm)
Figure 2. Muscle fiber diameter and fiber type distributions in Patients (A) 1 and (B) 2.
[1,8] except for mild CK elevation. Although the findings on nerve biopsies and cranial magnetic resonance imaging have suggested peripheral axonopathy [2,9] and central demyelinations [9,10], histopathologic descriptions of muscles have been limited. Selective type 1 fiber atrophy, which had not been reported previously, was observed in our patients. As compared to type 2 fiber atrophy, selective type 1 atrophy is uncommon [7] and known to occur in congenital nonprogressive myopathies (CNM), including nemaline myopathy, myotubular myopathy, central core disease, and congenital fiber type disproportion. Moreover, type 1 fiber predominance, which was reported in OCRS by Gobemado et al. [4] and is known to be a common finding in CNM [7], was found in Patient 2. Because of a lack of structural abnormalities, such as
nemaline bodies, central cores, or centrally placed nuclei, the muscle abnormalities in our patients are identical to those observed in congenital fiber type disproportion myopathy [7]. Selective type 1 fiber atrophy with type 1 fiber predominance is observed in various disease conditions, such as Pompe disease [11], experimental tenotomy [12], Krabbe leukodystrophy [13], and multiple sulfatase deficiency [14], in which peripheral nerves are involved. Although we could not obtain any evidence in our patients, abnormal neuronal influences upon muscle may play a role in the pathogenesis of the abnormal muscle fiber type distribution. OCRS, a multisystem disorder with some anomalous features, is probably induced by certain metabolic errors [5]. Gobernado et al. reported a defect in electron transport
Kohyamaet al: Lowe Syndrome 375
prior to c y t o c h r o m e , using a muscle biopsy specimen, in a patient with this disorder [4]. M u s c l e i n v o l v e m e n t may be a c o m m o n abnormality in various similar a n o m a l o u s s y n d r o m e s o f u n k n o w n etiology. For instance, fiber type disproportion associated with degenerative changes was reported in 2 siblings suffering from congenital m y o p a t h y with myasthenic features, high C K levels, and congenital cataracts [ 15]. Type l fiber p r e d o m i n a n c e with fiber necrosis, regeneration, and r i m m e d v a c u o l e formation was reported in Marinesco-SjOgren s y n d r o m e [16] which is characterized by congenital cataracts, ataxia, and mental retardation. It is u n k n o w n whether these m u s c l e findings inv o l v e a similar pathogenetic m e c h a n i s m . References
[1] Lowe CU, Terrey M, MacLachlan EA. Organic-aciduria, decreased renal ammonia production, hydrophthalmos, and mental retardation. A clinical entity. Am J Dis Child 1952;83:164-84. [2] Kornfeld M, Snyder RD, MacGee J, Appenzeller O. The oculocerebral-renal syndrome of Lowe. Neuromuscular components. Arch Neurol 1975;32:103-7. [3] Banerjee AK, Allen IV, McKee P. Oculo-cerebro-renal syndrome: Failure to demonstrate specific neuropathological abnormalities in four cases. Ir J Med Sci 1982;151:42-5. [4] Gobernado JM, Lousa M, Gimeno A, Gonsalvez M. Mitochondrial defects in Lowe's oculocerebrorenal syndrome. Arch Neurol 1984;41: 208-9.
376 PEDIATRIC NEUROLOGY Vol. 5 No. 6
[5] Wappner RS. Update: Lowcs ,,yndrnmc ~",~mpr I'hcr It~'~': 13:3-4. [61 Brooke MH, Engel WK. The histographic :lll:tlWl, ~,t Imm~ln muscle biopsies with regard to fiber types, 4. ('hil(lren'~ hinp~,ies. Neurology 1969; 19:591-605. [7] Dubowitz V. Definition of pathological changc~ seen m muscle biopsies. In: Dubowitz V. ed. Muscle biopsy. A practic:ll approach. London; Bailliere Tindall, 1985;82-128. [81 Abbassi V, Lowe CU, Calcagno PL. Ocuto-cerebro-renal syndrome. A review. Am J Dis Child 1968:115:145-68. [9] Charnas L, Bemar J, Pezeshkpour GH. Dalakus M, l-tarpcr GS, Gahl WA. MRI findings and peripheral neuropathy in Lowe's syndrome. Neuropediatrics 1988:19:7-9. [10] O'l"liama LA, Laster DW. Oculocerebrorenat syndrome: Case report with CT and MR correlates. AJNR 1987:8:555-7. [11] Martin JJ, Clara R, Centerick CH, Joris C. Is congenital fiber type disproportion a true myopathy? Acta Neurol Belg 1976;76:335-44. [12] Brooke MH, Kaiser KK. The use and abuse of muscle histochemistry. Ann NY Acad Sci 1974;228:121-44. [13] Dehkharghani F, Samal HB, Brewster MA, Roth S1. Congenital muscle fiber-type disproportion in Krabbe's leukodystrophy. Arch Neurol 1981;38:585-7. [14] Tachi N, Fujibayashi S, Wagatsuma K, Minami R, Imamura S. A case of multiple sulfatase deficiency with fiber type disproportion. No To Hattatsu 1984;16:205-9. [15] Nishida Y, Kobayashi T, Machi M, et al. Congenital myopathy with myasthenic features and congenital cataract in two siblings. J Neurol 1989;236:161-3. I16] Komiyama A, Nonaka I, Hirayama K. Muscle pathology in Marinesco-SjOgren syndrome. J Neurol Sci 1989;89:103-13.
Two brothers with the typical clinical features of oculocerebro-renal syndrome of Lowe exhibited delays in developmental milestones, muscular weakness and hypotonia, and high serum creatine kinase activity. The biopsied muscle revealed selective type 1 fiber atrophy and mild type 1 fiber predominance, similar to that observed in congenital fiber type disproportion myopathy. The abnormal fiber type distribution may be responsible for the common finding of muscle hypotonia in this syndrome.
motor development was delayed. He experienced a febrile tonic seizure at 9 months of age. He learned to walk at 3 years of age. On examination at 4 years, 9 months of age, he spoke only a few meaningful words. He was small in height (S.D. -2.4); however, no external anomaly was observed. He was hyperkinetic and had stereotypic hand movements. He stood up from the floor with mild Gowers' maneuver; he placed his hands on the floor and then lifted his hips and stood up. The facial and neck muscles were spared. No waddling gait, apparent muscle atrophy, or ataxia was observed. He had generalized muscle hypotonia. Deep tendon reflexes were absent and no pathologic reflexes could be elicited. Because of nystagmus in all directions, his eye positioning was unsteady, but ocular movement was not limited. Electroencephalography (EEG) revealed mild epileptic abnormalities, while cranial computed tomography (CT) was unremarkable. Except for an elevated serum CK level of 322 U/L (normal: < 60 U/L), blood chemistry results were within normal limits. Low molecular weight proteinuria, uricosuria, aminoaciduria, and calciuria were detected. Tubular reabsorption of phosphate (%TRP) was decreased (Table 1). Motor nerve conduction velocity was normal. Patient 2. The younger brother was born at term after a normal pregnancy, weighing 3,120 gm. He had congenital cataracts which were also removed by aspiration. He was a floppy infant with delayed motor Table 1.
Renal tubular functions in the patients
Patient 1
Patient 2
Normal Range
277 mg/dl
256 mg/dl
< 150 mg/dl
80,000 ~tg/L
88,000 ~tg/L
< 250 ~tg/L
196 ~tg/ml
152 lag/ml
0
Calcium/creatinine
0.58
1.16
< 0.20
Fractional excretion of uric acid
19.1%
23.7%
< 15.0%
Protein in urine Urinary fl2 microglobulin
Kohyama J, Niimura F, Kawashima K, Iwakawa Y, Nonaka I. Congenital fiber type disproportion myopathy in Lowe syndrome. Pediatr Neurol 1989;5:373-6.
Introduction The oculo-cerebro-renal syndrome (OCRS) of Lowe is characterized clinically by mental retardation, eye changes (i.e., glaucoma, congenital cataracts), and renal impairment [1]. Although the additional findings of muscle hypotonia and absence of deep tendon reflexes suggest probable muscle involvement, previous histologic muscle examinations have been inconclusive [2-5]. Because of elevated creatine kinase (CK) levels in 2 brothers with OCRS, muscle was biopsied and examined histologically.
Case Reports We report 2 brothers with nonconsanguineous, healthy parents. No neuromuscular or retinal disorders were observed in other family members. Patient 1. The elder brother was born at term after a normal pregnancy, weighing 2,970 gm. He had congenital cataracts which were removed by bilateral aspiration. He was a floppy infant and his psycho-
From the *Department of Pediatrics; Tsuchiura Kyoudou Hospital; Ibaraki, Japan; tlnstitute of Special Education; Tsukuba University; Tsububa, Japan; *Department of Pediatrics; Faculty of Medicine; Tokyo Medical and Dental University; Tokyo, Japan; and §Division of Ultrastructural Research; National Institute of Neuroscience; Kodaira, Japan.
Lysozyme
Percentage of tubular reabsorption of amino acids: Glycine
74.4
68.3
92.9 - 99.0
Valine
99.1
99.5
99.7 - 99.9
99.1
98.3 - 99.7
Methionine
100
Isoleucine
99.3
99.5
99.2 - 99.9
Leucine
99.3
99.2
99.6 - 99.9
Tyrosine
97.2
96.2
98.2 - 99.3
Phenylalanine
98.7
97.7
98.8 - 99.7
Histidine
81.1
72.6
90.3 - 98.4
Lysine
95.5
94.0
98.5 - 99.8
99.3
99.0 - 99.9
Arginine Percentage of tubular reabsorption of phosphate
100 84
50
89 - 98
Communications should be addressed to: Dr. Kohyama; Department of Pediatrics; Tsuchiura Kyoudou Hospital; Manabe-Shinmachi 11-7; Tsuchiura, Ibaraki 300, Japan. Received August 15, 1989; accepted September 21, 1989.
Kohyama et al: Lowe Syndrome
373
Figure I. (A) Muscle biopsy J}'om Patient 2: ATPase stain with preincubation at pH 4.6. Although type 1 (1). 2A (A), and 2B (B) fibers are distributed in a mosaic pattern, type I fibers are selective[y atrophic'. Original magnification, x60. (B) Muscle biopsy from Patient 1." NADH-TR stain. Small type I fibers have a core-like. moth-eaten appearanee (arrow). Original magnification, x120. milestones. He experienced a febrile tonic seizure at 1 year, 6 months of age. During the most recent clinical examination at 3 years, 4 months of age, he was small in height (S.D. -3.7) and could stand only with support because of mild muscle weakness. He spoke only a few meaningful words. His physical and neurologic condition was similar to that of his brother. He was mentally retarded and had nystagmus and decreased muscle tone with hypoactive tendon reflexes. Laboratory examination also demonstrated similar results, including an elevated CK level of 186 U/L, low molecular weight proteinuria, uricosuria, aminoaciduria, calciuria, and remarkably decreased %TRP (Table 1). EEG demonstrated an epileptic abnormality, while cranial CT was unremarkable. Muscle Pathology. Specimens were obtained from their biceps brachii muscles. Serial frozen sections were stained with hematoxylin and eosin, and by various histochemical methods, including NADHtetrazolium rednctase (NADH-TR), modified Gomori trichrome, oil red O, periodic acid Schiff (PAS), acid phosphatase, alkaline phosphatase, cytochrome c oxidase, and myosin adenosine triphosphatase (ATPase) with alkaline and acid preincubation.
374
PEDIATRIC NEUROLOGY
Vol. 5 No. 6
In both patients, the muscle disclosed no fiber necrosis or increased connective or adipose tissue. On ATPase staining (Fig 1A), type 1, 2A, and 2B fibers were distributed in a normal mosaic pattern, while type 1 fibers were more than 12% smaller in diameter than normal type 2 fibers (Fig 2) [6]. No fiber type deficiency or increase in type 2C fibers was observed. Type 1 fibers were predominant (60% vs normal: < 55% [6]) in Patient 2. Variability coefficients were less than 250 in both specimens [7]. On NADH-TR staining of the muscle of Patient 1, scattered fibers were observed with disorganized intermyofibrillar networks and a multiple core-like or moth-eaten appearance (Fig 1B). Modified Gomori trichrome staining revealed no ragged-red fibers or nemaline bodies. There was no excess accumulation of PAS or oil,red-O positive material.
Discussion The clinical features of our patients, including mental retardation,
ocular
abnormalities,
renal manifestations,
a n d n e u r a l i n v o l v e m e n t , all w e r e c h a r a c t e r i s t i c o f O C R S
MuscleFiberType A
MeanDiameter(pm) centageof Fibers
i_
2C []
I
2B 2A X O 25.9 22.4 20'4 50% 22.6% 27%
19.7 0.4%
LL 50. O f,_
Q)
.O E
/
Z
,o
/ ....-~..._~.
i x-
/
/
10
15
•%-'-., 20
25
30
35
40
Diameter (pm)
MuscleFiberType
1
i
~ •
100" U3 L
Q)
..O LL o
.w
f,-
Q)
..O 50" E
MeanDiameter(pro) ~ c e n t a g e of Fibers
2A
2B
2C
©
x
[]
17.7 18.3 21.3 9.9 60%
10%
29%
1%
Z
0 5
10
15
2'0
2's
3'o
Diameter (pm)
Figure 2. Muscle fiber diameter and fiber type distributions in Patients (A) 1 and (B) 2.
[1,8] except for mild CK elevation. Although the findings on nerve biopsies and cranial magnetic resonance imaging have suggested peripheral axonopathy [2,9] and central demyelinations [9,10], histopathologic descriptions of muscles have been limited. Selective type 1 fiber atrophy, which had not been reported previously, was observed in our patients. As compared to type 2 fiber atrophy, selective type 1 atrophy is uncommon [7] and known to occur in congenital nonprogressive myopathies (CNM), including nemaline myopathy, myotubular myopathy, central core disease, and congenital fiber type disproportion. Moreover, type 1 fiber predominance, which was reported in OCRS by Gobemado et al. [4] and is known to be a common finding in CNM [7], was found in Patient 2. Because of a lack of structural abnormalities, such as
nemaline bodies, central cores, or centrally placed nuclei, the muscle abnormalities in our patients are identical to those observed in congenital fiber type disproportion myopathy [7]. Selective type 1 fiber atrophy with type 1 fiber predominance is observed in various disease conditions, such as Pompe disease [11], experimental tenotomy [12], Krabbe leukodystrophy [13], and multiple sulfatase deficiency [14], in which peripheral nerves are involved. Although we could not obtain any evidence in our patients, abnormal neuronal influences upon muscle may play a role in the pathogenesis of the abnormal muscle fiber type distribution. OCRS, a multisystem disorder with some anomalous features, is probably induced by certain metabolic errors [5]. Gobernado et al. reported a defect in electron transport
Kohyamaet al: Lowe Syndrome 375
prior to c y t o c h r o m e , using a muscle biopsy specimen, in a patient with this disorder [4]. M u s c l e i n v o l v e m e n t may be a c o m m o n abnormality in various similar a n o m a l o u s s y n d r o m e s o f u n k n o w n etiology. For instance, fiber type disproportion associated with degenerative changes was reported in 2 siblings suffering from congenital m y o p a t h y with myasthenic features, high C K levels, and congenital cataracts [ 15]. Type l fiber p r e d o m i n a n c e with fiber necrosis, regeneration, and r i m m e d v a c u o l e formation was reported in Marinesco-SjOgren s y n d r o m e [16] which is characterized by congenital cataracts, ataxia, and mental retardation. It is u n k n o w n whether these m u s c l e findings inv o l v e a similar pathogenetic m e c h a n i s m . References
[1] Lowe CU, Terrey M, MacLachlan EA. Organic-aciduria, decreased renal ammonia production, hydrophthalmos, and mental retardation. A clinical entity. Am J Dis Child 1952;83:164-84. [2] Kornfeld M, Snyder RD, MacGee J, Appenzeller O. The oculocerebral-renal syndrome of Lowe. Neuromuscular components. Arch Neurol 1975;32:103-7. [3] Banerjee AK, Allen IV, McKee P. Oculo-cerebro-renal syndrome: Failure to demonstrate specific neuropathological abnormalities in four cases. Ir J Med Sci 1982;151:42-5. [4] Gobernado JM, Lousa M, Gimeno A, Gonsalvez M. Mitochondrial defects in Lowe's oculocerebrorenal syndrome. Arch Neurol 1984;41: 208-9.
376 PEDIATRIC NEUROLOGY Vol. 5 No. 6
[5] Wappner RS. Update: Lowcs ,,yndrnmc ~",~mpr I'hcr It~'~': 13:3-4. [61 Brooke MH, Engel WK. The histographic :lll:tlWl, ~,t Imm~ln muscle biopsies with regard to fiber types, 4. ('hil(lren'~ hinp~,ies. Neurology 1969; 19:591-605. [7] Dubowitz V. Definition of pathological changc~ seen m muscle biopsies. In: Dubowitz V. ed. Muscle biopsy. A practic:ll approach. London; Bailliere Tindall, 1985;82-128. [81 Abbassi V, Lowe CU, Calcagno PL. Ocuto-cerebro-renal syndrome. A review. Am J Dis Child 1968:115:145-68. [9] Charnas L, Bemar J, Pezeshkpour GH. Dalakus M, l-tarpcr GS, Gahl WA. MRI findings and peripheral neuropathy in Lowe's syndrome. Neuropediatrics 1988:19:7-9. [10] O'l"liama LA, Laster DW. Oculocerebrorenat syndrome: Case report with CT and MR correlates. AJNR 1987:8:555-7. [11] Martin JJ, Clara R, Centerick CH, Joris C. Is congenital fiber type disproportion a true myopathy? Acta Neurol Belg 1976;76:335-44. [12] Brooke MH, Kaiser KK. The use and abuse of muscle histochemistry. Ann NY Acad Sci 1974;228:121-44. [13] Dehkharghani F, Samal HB, Brewster MA, Roth S1. Congenital muscle fiber-type disproportion in Krabbe's leukodystrophy. Arch Neurol 1981;38:585-7. [14] Tachi N, Fujibayashi S, Wagatsuma K, Minami R, Imamura S. A case of multiple sulfatase deficiency with fiber type disproportion. No To Hattatsu 1984;16:205-9. [15] Nishida Y, Kobayashi T, Machi M, et al. Congenital myopathy with myasthenic features and congenital cataract in two siblings. J Neurol 1989;236:161-3. I16] Komiyama A, Nonaka I, Hirayama K. Muscle pathology in Marinesco-SjOgren syndrome. J Neurol Sci 1989;89:103-13.