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Infantile Glaucoma in Down's Syndrome (Trisomy 21): Reply
638
November, 1988
AMERICAN JOURNAL OF OPHTHALMOLOGY
Reference
References
1. Frueh, B. R., and Musch, D. C : Treatment of facial spasm with botulinum toxin. An interim re port. Ophthalmology 93:917, 1986.
1. Jerndal, T.: Goniodysgenesis and hereditary ju venile glaucoma. Acta Ophthalmol. Suppl. 107,1970. 2. Bardelli, A. M., Hadjistilianou, T., and Trezzotti, R.: Etiology of congenital glaucoma. Genetic and extragenetic factors. Ophthalmol. Paediatr. Genet. 6:25, 1985.
Reply Infantile Glaucoma in Down's Syndrome (Trisomy 21) EDITOR: In the article "Infantile glaucoma in Down's syndrome (Trisomy 21)" by E. I. Traboulsi, E. Levine, M. B. Mets, E. S. Parelhoff, J. F. O'Neill, and D. E. Gaasterland (Am. J. Oph thalmol. 105:389, April 1988), two important issues remain unclear. Infantile congenital glaucoma is not an ab normality like cataract or keratoconus. The appropriate abnormality in the actual context is goniodysgenesis, the origin of congenital glaucoma. The omission of this key concept inevitably leads to confusion in the subse quent consideration of heredity. Inherited infantile congenital glaucoma is caused by genetic goniodysgenesis, which is usually autosomal dominant. The literature contains several examples of dominant gonio dysgenesis with glaucoma. In 1970 I described a child from a large family who was born with Down's syndrome and large hazy corneas. 1 Intraocular pressure was R.E.: 25 mm Hg and L.E.: 26 mm Hg. Congenital glaucoma was diagnosed. This pedigree thus appears to be analogous to that described by Bardelli, Had jistilianou, and Trezzotti, 2 which was referred to by the authors. In both pedigrees, one spo radic case of Down's syndrome occurred against a background of family glaucoma with dominant goniodysgenesis. Finally, the conclusion that sporadic cases of Down's syndrome with infantile congenital glaucoma would add further evidence to the genetic heterogeneity of the latter seems somewhat hasty. TORD JERNDAL, M.D. Gothenburg, Sweden
EDITOR: Dr. Jerndal described a large family with anterior segment dysgenesis (abnormal angle structures, iris hypoplasia, corectopia), that he referred to as goniodysgenesis, and juve nile glaucoma. 1 The association between ante rior segment dysgenesis and juvenile glauco ma is well known. Anterior segment dysgenesis is inherited in an autosomal domi nant fashion. Inherited infantile glaucoma, on the other hand, is generally autosomal reces sive and is presumably the result of a single gene defect, but dominant, multifactorial, and sporadic cases of infantile glaucoma also oc cur. 2 · 3 The pathogenesis of infantile glaucoma is thought to be the result of trabeculodysgenesis or goniodysgenesis in the sense that the filtering angle structures are formed ab normally and no gross abnormalities of the iris are found. Dr. Jerndal's patients and other patients with what we now call anterior segment dysgenesis all have iris abnormali ties. One patient in the family described by Dr. Jerndal 1 had Down's syndrome and congenital glaucoma. If this patient had also inherited the abnormal gene for anterior segment dys genesis, he would, in our opinion, have two predisposing factors for glaucoma: anterior segment dysgenesis and the malformation of the angle tissues presumably caused by the trisomie state. Indeed, this patient was one of only two among many patients in this family who had infantile glaucoma; in the others, glaucoma developed in the teens, 20s, or later in life. In response to Dr. Jerndal's criticism of our conclusion that the finding of infantile glauco ma in some patients with Down's syndrome adds further evidence to the genetic heteroge neity of the former, we continue to believe that abnormal development of the filtration
Correspondence
Vol. 106, No. 5
a n g l e m a y r e s u l t from a v a r i e t y of c h r o m o s o mal or single g e n e a b n o r m a l i t i e s . For e x a m p l e , a trisomie s t a t e m a y p r o d u c e two copies of a " r e c e s s i v e " g e n e t h a t w o u l d lead to t h e a b n o r m a l d e v e l o p m e n t a l defect. ELIAS I. TRABOULSI, M.D. ELLIOT LEVINE, M.D. Washington, D.C. MARILYN B. METS, M.D. Chicago, Illinois EDWARD S. PARELHOFF, M.D. JOHN F. O'NEILL, M.D. DOUGLAS E. GAASTERLAND, M.D. Washington, D.C.
References 1. Jerndal, T.: Goniodysgenesis and hereditary juvenile glaucoma. Acta Ophthalmol. Suppl. 107, 1970. 2. Demenais, F., Bonaiti, C , Briard, M. L., Feingold, J., and Frezal,J.: Congenital glaucoma. Genetic models. Hum. Genet. 46:305, 1979. 3. Gencik, A., Gencikova, A., and Gerinee, A.: Genetic heterogeneity of congenital glaucoma. Clin. Genet. 17:241, 1980.
Normal a-L-Fucosidase and Other Lysosomal Enzyme Activities in Progressive Cone Dystrophy EDITOR: In t h e article, " N o r m a l ct-L-fucosidase a n d o t h e r l y s o s o m a l e n z y m e activities in p r o g r e s sive c o n e d y s t r o p h y " b y V. D. S t o u m b o s , R. G. Weleber, a n d N . G. K e n n a w a y ( A m . J. O p h t h a l m o l . 106:11, July 1988), t h e a u t h o r s cite o u r article 1 a n d s t a t e t h a t " t h e p r e v i o u s o b s e r v a t i o n of low fucosidase activity m a y have been spurious." Since t h e p u b l i c a t i o n of o u r p a p e r , w e h a v e e x a m i n e d five o t h e r p a t i e n t s w i t h c o n e d y s t r o p h y , b u t w e failed to find low f u c o s i d a s e activity. We c o n d u c t e d f u r t h e r b i o c h e m i c a l e x a m i n a t i o n of t h e p r e v i o u s l y d e s c r i b e d p a tient (Case 1), a n d a n a b n o r m a l s e r u m p H e n z y m e activity c u r v e a n d a n i n c r e a s e d a m o u n t of f u c o s e - c o n t a i n i n g s u b s t a n c e s ex creted in t h e u r i n e w e r e o b s e r v e d ( u n p u b lished d a t a ) . T h e r e f o r e , a deficiency of a n iso-
639
z y m e a n d a b n o r m a l fucose m e t a b o l i s m m a y b e s t r o n g l y s u g g e s t e d in this p a t i e n t . We also f o u n d t h a t α-L-fucosidase activity w a s h i g h e r in t h e m a c u l a t h a n in o t h e r a r e a s of n o r m a l h u m a n r e t i n a a n d c h o r o i d . 2 C o n e f u n c t i o n in t h e m a c u l a m a y b e p r e d o m i n a n t l y affected in t h e e n z y m e deficiency. S y m p t o m s d e v e l o p oc casionally in h e t e r o z y g o u s i n d i v i d u a l s or in d i v i d u a l s w i t h low e n z y m e activity; for e x a m p l e , p r e s e n i l e cataract in p a t i e n t s w i t h a half g a l a c t o k i n a s e activity 3 a n d a n e p i s o d e of u n c o n s c i o u s n e s s in y o u n g a d u l t p a t i e n t s w i t h 10% to 20% activity of a r g i n i n o s u c c i n a t e s y n thetase.4 We b e l i e v e t h a t c o n e d y s t r o p h y is h e t e r o g e n e o u s , t h a t c o n c u r r e n c e of c o n e d y s t r o p h y a n d low a-L-fucosidase activity m a y b e u n c o m m o n , t h a t t h e low activity in o u r p a t i e n t s is n o t s p u r i o u s , a n d t h a t t h e r e l a t i o n s h i p b e t w e e n t h e low e n z y m e activity a n d t h e p a t h o g e n e s i s of t h e d i s e a s e s h o u l d b e further s t u d ied. SEIJI HAYASAKA, M.D. Izumo, Japan HITOSHI OKABE, M.D. Sendai, Japan KATSUYOSHI MIZUNO, M.D. Gifu, Japan
References 1. Hayasaka, S., Nakazawa, M., Okabe, H., Masuda, K., and Mizuno, K.: Progressive cone dystro phy associated with low a-L-fucosidase activity in serum and leukocytes. Am. J. Ophthalmol. 99:681, 1985. 2. Hayasaka, S., Noda, S., and Setogawa, T.: Re gional distribution of N-acetyl-ß-D-glucosaminidase and a-L-fucosidase activities in the human retina and choroid. Ophthalmic Res. In press. 3. Stamboliart, D., Scarpino-Myers, V., Eagle, R. C , Jr., Hodes, B., and Harris, H.: Cataracts in patients heterozygous for galactokinase deficiency. Invest. Ophthalmol. Vis. Sci. 27:429, 1986. 4. Hayasaka, S., Yabata, K., Ohmura, M., Nomu ra, H., and Takase, S.: Papilloedema in late-onset citrullinaemia. Report of second case. Graefes Arch. Clin. Exp. Ophthalmol. 221:262, 1984.
Reply EDITOR: We a p p r e c i a t e t h e c o m m e n t s of D r s . H a y a saka, Okabe, and Mizuno and the additional
November, 1988
AMERICAN JOURNAL OF OPHTHALMOLOGY
Reference
References
1. Frueh, B. R., and Musch, D. C : Treatment of facial spasm with botulinum toxin. An interim re port. Ophthalmology 93:917, 1986.
1. Jerndal, T.: Goniodysgenesis and hereditary ju venile glaucoma. Acta Ophthalmol. Suppl. 107,1970. 2. Bardelli, A. M., Hadjistilianou, T., and Trezzotti, R.: Etiology of congenital glaucoma. Genetic and extragenetic factors. Ophthalmol. Paediatr. Genet. 6:25, 1985.
Reply Infantile Glaucoma in Down's Syndrome (Trisomy 21) EDITOR: In the article "Infantile glaucoma in Down's syndrome (Trisomy 21)" by E. I. Traboulsi, E. Levine, M. B. Mets, E. S. Parelhoff, J. F. O'Neill, and D. E. Gaasterland (Am. J. Oph thalmol. 105:389, April 1988), two important issues remain unclear. Infantile congenital glaucoma is not an ab normality like cataract or keratoconus. The appropriate abnormality in the actual context is goniodysgenesis, the origin of congenital glaucoma. The omission of this key concept inevitably leads to confusion in the subse quent consideration of heredity. Inherited infantile congenital glaucoma is caused by genetic goniodysgenesis, which is usually autosomal dominant. The literature contains several examples of dominant gonio dysgenesis with glaucoma. In 1970 I described a child from a large family who was born with Down's syndrome and large hazy corneas. 1 Intraocular pressure was R.E.: 25 mm Hg and L.E.: 26 mm Hg. Congenital glaucoma was diagnosed. This pedigree thus appears to be analogous to that described by Bardelli, Had jistilianou, and Trezzotti, 2 which was referred to by the authors. In both pedigrees, one spo radic case of Down's syndrome occurred against a background of family glaucoma with dominant goniodysgenesis. Finally, the conclusion that sporadic cases of Down's syndrome with infantile congenital glaucoma would add further evidence to the genetic heterogeneity of the latter seems somewhat hasty. TORD JERNDAL, M.D. Gothenburg, Sweden
EDITOR: Dr. Jerndal described a large family with anterior segment dysgenesis (abnormal angle structures, iris hypoplasia, corectopia), that he referred to as goniodysgenesis, and juve nile glaucoma. 1 The association between ante rior segment dysgenesis and juvenile glauco ma is well known. Anterior segment dysgenesis is inherited in an autosomal domi nant fashion. Inherited infantile glaucoma, on the other hand, is generally autosomal reces sive and is presumably the result of a single gene defect, but dominant, multifactorial, and sporadic cases of infantile glaucoma also oc cur. 2 · 3 The pathogenesis of infantile glaucoma is thought to be the result of trabeculodysgenesis or goniodysgenesis in the sense that the filtering angle structures are formed ab normally and no gross abnormalities of the iris are found. Dr. Jerndal's patients and other patients with what we now call anterior segment dysgenesis all have iris abnormali ties. One patient in the family described by Dr. Jerndal 1 had Down's syndrome and congenital glaucoma. If this patient had also inherited the abnormal gene for anterior segment dys genesis, he would, in our opinion, have two predisposing factors for glaucoma: anterior segment dysgenesis and the malformation of the angle tissues presumably caused by the trisomie state. Indeed, this patient was one of only two among many patients in this family who had infantile glaucoma; in the others, glaucoma developed in the teens, 20s, or later in life. In response to Dr. Jerndal's criticism of our conclusion that the finding of infantile glauco ma in some patients with Down's syndrome adds further evidence to the genetic heteroge neity of the former, we continue to believe that abnormal development of the filtration
Correspondence
Vol. 106, No. 5
a n g l e m a y r e s u l t from a v a r i e t y of c h r o m o s o mal or single g e n e a b n o r m a l i t i e s . For e x a m p l e , a trisomie s t a t e m a y p r o d u c e two copies of a " r e c e s s i v e " g e n e t h a t w o u l d lead to t h e a b n o r m a l d e v e l o p m e n t a l defect. ELIAS I. TRABOULSI, M.D. ELLIOT LEVINE, M.D. Washington, D.C. MARILYN B. METS, M.D. Chicago, Illinois EDWARD S. PARELHOFF, M.D. JOHN F. O'NEILL, M.D. DOUGLAS E. GAASTERLAND, M.D. Washington, D.C.
References 1. Jerndal, T.: Goniodysgenesis and hereditary juvenile glaucoma. Acta Ophthalmol. Suppl. 107, 1970. 2. Demenais, F., Bonaiti, C , Briard, M. L., Feingold, J., and Frezal,J.: Congenital glaucoma. Genetic models. Hum. Genet. 46:305, 1979. 3. Gencik, A., Gencikova, A., and Gerinee, A.: Genetic heterogeneity of congenital glaucoma. Clin. Genet. 17:241, 1980.
Normal a-L-Fucosidase and Other Lysosomal Enzyme Activities in Progressive Cone Dystrophy EDITOR: In t h e article, " N o r m a l ct-L-fucosidase a n d o t h e r l y s o s o m a l e n z y m e activities in p r o g r e s sive c o n e d y s t r o p h y " b y V. D. S t o u m b o s , R. G. Weleber, a n d N . G. K e n n a w a y ( A m . J. O p h t h a l m o l . 106:11, July 1988), t h e a u t h o r s cite o u r article 1 a n d s t a t e t h a t " t h e p r e v i o u s o b s e r v a t i o n of low fucosidase activity m a y have been spurious." Since t h e p u b l i c a t i o n of o u r p a p e r , w e h a v e e x a m i n e d five o t h e r p a t i e n t s w i t h c o n e d y s t r o p h y , b u t w e failed to find low f u c o s i d a s e activity. We c o n d u c t e d f u r t h e r b i o c h e m i c a l e x a m i n a t i o n of t h e p r e v i o u s l y d e s c r i b e d p a tient (Case 1), a n d a n a b n o r m a l s e r u m p H e n z y m e activity c u r v e a n d a n i n c r e a s e d a m o u n t of f u c o s e - c o n t a i n i n g s u b s t a n c e s ex creted in t h e u r i n e w e r e o b s e r v e d ( u n p u b lished d a t a ) . T h e r e f o r e , a deficiency of a n iso-
639
z y m e a n d a b n o r m a l fucose m e t a b o l i s m m a y b e s t r o n g l y s u g g e s t e d in this p a t i e n t . We also f o u n d t h a t α-L-fucosidase activity w a s h i g h e r in t h e m a c u l a t h a n in o t h e r a r e a s of n o r m a l h u m a n r e t i n a a n d c h o r o i d . 2 C o n e f u n c t i o n in t h e m a c u l a m a y b e p r e d o m i n a n t l y affected in t h e e n z y m e deficiency. S y m p t o m s d e v e l o p oc casionally in h e t e r o z y g o u s i n d i v i d u a l s or in d i v i d u a l s w i t h low e n z y m e activity; for e x a m p l e , p r e s e n i l e cataract in p a t i e n t s w i t h a half g a l a c t o k i n a s e activity 3 a n d a n e p i s o d e of u n c o n s c i o u s n e s s in y o u n g a d u l t p a t i e n t s w i t h 10% to 20% activity of a r g i n i n o s u c c i n a t e s y n thetase.4 We b e l i e v e t h a t c o n e d y s t r o p h y is h e t e r o g e n e o u s , t h a t c o n c u r r e n c e of c o n e d y s t r o p h y a n d low a-L-fucosidase activity m a y b e u n c o m m o n , t h a t t h e low activity in o u r p a t i e n t s is n o t s p u r i o u s , a n d t h a t t h e r e l a t i o n s h i p b e t w e e n t h e low e n z y m e activity a n d t h e p a t h o g e n e s i s of t h e d i s e a s e s h o u l d b e further s t u d ied. SEIJI HAYASAKA, M.D. Izumo, Japan HITOSHI OKABE, M.D. Sendai, Japan KATSUYOSHI MIZUNO, M.D. Gifu, Japan
References 1. Hayasaka, S., Nakazawa, M., Okabe, H., Masuda, K., and Mizuno, K.: Progressive cone dystro phy associated with low a-L-fucosidase activity in serum and leukocytes. Am. J. Ophthalmol. 99:681, 1985. 2. Hayasaka, S., Noda, S., and Setogawa, T.: Re gional distribution of N-acetyl-ß-D-glucosaminidase and a-L-fucosidase activities in the human retina and choroid. Ophthalmic Res. In press. 3. Stamboliart, D., Scarpino-Myers, V., Eagle, R. C , Jr., Hodes, B., and Harris, H.: Cataracts in patients heterozygous for galactokinase deficiency. Invest. Ophthalmol. Vis. Sci. 27:429, 1986. 4. Hayasaka, S., Yabata, K., Ohmura, M., Nomu ra, H., and Takase, S.: Papilloedema in late-onset citrullinaemia. Report of second case. Graefes Arch. Clin. Exp. Ophthalmol. 221:262, 1984.
Reply EDITOR: We a p p r e c i a t e t h e c o m m e n t s of D r s . H a y a saka, Okabe, and Mizuno and the additional