Europ. J. Pediat. 121, 59--62 (1975) 9 by Springer-Verlag 1975
Laurence-Moon-Biedl Syndrome Associated with Diabetes Insipidus Neurohormonalis Peter Koepp Universiti~ts-Kinderklinik,Hamburg l~eeeived June 25, 1975
Abstract. The case of a girl with Laurence-Moon-Biedl syndrome without polydactyly is described. Additional features were small stature, diabetes insipidus neurohormonalis and a renal disorder. The diabetes insipidus neurohormonalis was successfully treated with a new vasopressin analogue, DDAVP. The importance of renal studies in patients with LaurenceMoon-Biedl syndrome is emphasized. Key words: Laurence-~oon-Biedl syndrome - - Diabetes insipidus neurohormonalis - Renal disorder.
Zusammen/assung. Es wird eine Patientin mit Laurence-Moon-Biedl-Syndromohne Polydaktylie beschrieben. Die Patientin hatte zus~tzlich Minderwuchs, neurohormonalen Diabetes insipidus und eine Nierenerkrankung. Der Diabetes insipidus neurohormonalis wird erfolgreich behandelt mit einem neuen Vasopressinanalog, dem DDAVP. Die Wichtigkeit yon Untersuchungen der Nierenfunktion bei Patienten mit Laurence-Moon-Biedl-Syndromwird betont.
The Laurence-Moon-Biedl s y n d r o m e (LMB syndrome) consists of obesity, m e n t a l deficiency, retinitis pigmentosa, p o l y d a c t y l y a n d h y p o g o n a d i s m . There is n o difficulty i n the diagnosis of completely developed cases, b u t t h e diagnosis m a y be difficult i n atypical forms of t h e syndrome, p a r t i c u l a r l y those associated with other a b n o r m a l i t i e s (Klein a n d A m m a n n , 1969). This is a report of t h e clinical findings i n a girl with LMB s y n d r o m e associated with diabetes insipidus neuroh o r m o n a l i s a n d a r e n a l disorder.
Case Report The patient was born with an apgar score of 10. At 3 days of age a seizure was noticed. Hypoglycemia (17 rag/100 ml) was found once but there were no further hypoglycemic episodes. Poor vision with irregular eye movements was noticed at 2 years of age and fundoseopy revealed optic nerve atrophy. Electroretinography (ERG) was normal. At 5 years of age, an extinguished ERG was found, and retinitis pigmentosa with optic nerve atrophy and hypermetropia were found on ophthalmoscopic examination. At the age of 2 months she started to have frequent episodes of fever of undetermined origin, during which she was comatose twice and once had a seizure. Hypernatremia (150--160 mval) and hyperchloremia (112--120 mval) together with a low specific gravity of urine (1002--1014) were constant findings. At the age of 7 years she was admitted to our hospital and was found to be grossly retarded and hypotonic with a developmental age of 2 years, an overweight of 3000 g (90th percentile according to length), length of 108 em (below 3rd percentile for age) and mierocephaly (below 3rd percentile for age). She had coxa valga antetorsa and talus vertiealis. Blood smear, BUN and serum creatinine
60
P. Koepp Body
~
~mperature 4039. 37 Chloride mval Serum
120. 110. 10090-
Spec. Gravity 1020. Urine 1010-
daily fluid intake - -
2000 m!
I - - 9 0 0 - 700 ml
*
normal Sod. restricted diet diet I I7 1-50.-{-1200--~ mval / day cal Pitressin
DDAVP Qlml
5 IE ira.
25. Jan.
l ~ Feb.
10.
15
20.
25.
1. March. 1975
~ig. l. Body temperature, specific gravity of urine, serum chloride concentration and fluid intake of a patient with Laurenee-Moon-Biedl syndrome with diabetes insipidus neurohormonalis before and after treatment with DDAVP
were normal, but serum sodium and serum chloride concentrations were increased (150--163 and 107--121 royal, respectively). Urine osmolarity was low (80 mosmol) and serum osmolarity was increased (330 mosmol, normal 275--295 mosmol) (Fig. 1). Intravenous pyelography showed hypoplastic kidneys; biopsy revealed glomerular dysplasia histologically. Special Investigations A water deprivation test was performed; there was only a slight rise in urine osmolarity while the patient lost more than 5~ of b o d y weight, but she became somnolent and the test was discontinued. A vasopressin test was performed thereafter (Fig. 2). A rise of urine osmolarity from 50 to 410 mosmol and normalization of serum osmolarity (330 mosmol before and 290 mosmol 60 min after injection of 5 I E Pitressin | intravenously) disclosed vasopressin sensitive diabetes insipidus. Treatment was successful with a new synthetic vasopressin analogue, D D A V P (1-deamino-8-D-arginine vasopressin) (Aronson et al., 1973) (Fig. 1).
Laurence-Moon-Biedl Syndrome URINE
61
5 IE PITRE$SIN Lv, [ (aqueous solution)
OSMOLARITY [m osmoI]
_! 356 250.
15C
56 TIME
SERUM OSMOLARITY
[m osmol]
336 310 290
--yj
270
Fig. 2. Serum and urine osmolarity during vasopressin test in a patient with Laurence-MoonBiedl syndrome with diabetes insipidus neurohormonalis
Discussion
Of the characteristic features of the LMB syndrome, our patient lacked the polydactyly and hypogenitalism could not be demonstrated in the female infant. But she also displayed several unusual features: diabetes insipidus neurohormohalls, small stature and a renal disorder. The association of LMB syndrome with diabetes insipidus neurohormonalis has been reported occasionally (Krill et al., 1961; Warkany et al., 1937). In our patient the endocrine abnormality was not diagnosed until the 6th year of age. Since hypernatremia b y itself is a handicap to the development and function of the brain (Cooke and Ottenheimer, 1960), untreated diabetes insipidus neurohormonalis might well have contributed to some degree of the cerebral damage in our patient. Small stature was one of the symptoms of Biedl's patients (Biedl, 1922) but has rarely been reported thereafter (Warkany et al., 1937). The diabetes insipidus neurohormonalis might also have contributed to this manifestation. Renal disorders are of special importance for patients with LMB syndrome since they are found in almost all postmortem examinations (Bauman and Hogan, 1973) and they are a frequent cause of death in these patients (Alton and McDonald, 1973). Consequently intravenous pyelography and possibly renal histology should
62
P. Koepp
be p e r f o r m e d in all L M B p a t i e n t s in o r d e r t o disclose t h e r e n a l disorder, which t h e n m i g h t be successfully t r e a t e d a n d f u r t h e r d a m a g e p r e v e n t e d .
References Alton, D. J., McDonald, P. : Urographie findings in the Bardet-Biedl syndrome. Radiology 109, 659 (1973) Aronson, A. S., Andersson, K.-E., Bergstrand, C. G., Mulder, J. L. : Treatment of diabetes insipidus in children with DDAVP, a new synthetic analogue of vasoloressin. Acta 9aediat. stand. 62, 133 (1973) Bauman, M. L., Hogan, G. R.: Laurence-Moon-Biedl syndrome. Amer. J. Dis. Child. 126, 119 (1973) Biedl, A. : Ein Geschwisterpaar mit adiposogenitaler Dystrophie. D~seh. reed. Wsehr. 48, 1630 (1922) Cooke, R. E., Ottenheimer, E. J. : Clinical and experimental interrelations of sodium and the central nervous system. Advanc. Pediar XI, 81 (1960) Klein, D., Ammann, F.: The syndrome of Laurence-Moon-Biedl and allied diseases in Switzerland. J. neurol. Sci. 9, 479 (1969) Krill, A. E., Folk, E., Rosenthal, I. M.: Electroretinography in the Laurence-Moon-Biedl syndrome. Amer. J. Dis. Child. 102, 205 (1961) Warkany, J., Frauenberger, G. S., Mitchell, A. G. : Heredofamilial deviations: The LaurenceMoomBiedl synch'ome. Amer. J. Dis. Child. 53, 455 (1937) Dr. P. Koepp Universit~ts-Kinderklinik D-2000 Hamburg 20, MartinistraBe 52 Federal Republic of Germany
Laurence-Moon-Biedl Syndrome Associated with Diabetes Insipidus Neurohormonalis Peter Koepp Universiti~ts-Kinderklinik,Hamburg l~eeeived June 25, 1975
Abstract. The case of a girl with Laurence-Moon-Biedl syndrome without polydactyly is described. Additional features were small stature, diabetes insipidus neurohormonalis and a renal disorder. The diabetes insipidus neurohormonalis was successfully treated with a new vasopressin analogue, DDAVP. The importance of renal studies in patients with LaurenceMoon-Biedl syndrome is emphasized. Key words: Laurence-~oon-Biedl syndrome - - Diabetes insipidus neurohormonalis - Renal disorder.
Zusammen/assung. Es wird eine Patientin mit Laurence-Moon-Biedl-Syndromohne Polydaktylie beschrieben. Die Patientin hatte zus~tzlich Minderwuchs, neurohormonalen Diabetes insipidus und eine Nierenerkrankung. Der Diabetes insipidus neurohormonalis wird erfolgreich behandelt mit einem neuen Vasopressinanalog, dem DDAVP. Die Wichtigkeit yon Untersuchungen der Nierenfunktion bei Patienten mit Laurence-Moon-Biedl-Syndromwird betont.
The Laurence-Moon-Biedl s y n d r o m e (LMB syndrome) consists of obesity, m e n t a l deficiency, retinitis pigmentosa, p o l y d a c t y l y a n d h y p o g o n a d i s m . There is n o difficulty i n the diagnosis of completely developed cases, b u t t h e diagnosis m a y be difficult i n atypical forms of t h e syndrome, p a r t i c u l a r l y those associated with other a b n o r m a l i t i e s (Klein a n d A m m a n n , 1969). This is a report of t h e clinical findings i n a girl with LMB s y n d r o m e associated with diabetes insipidus neuroh o r m o n a l i s a n d a r e n a l disorder.
Case Report The patient was born with an apgar score of 10. At 3 days of age a seizure was noticed. Hypoglycemia (17 rag/100 ml) was found once but there were no further hypoglycemic episodes. Poor vision with irregular eye movements was noticed at 2 years of age and fundoseopy revealed optic nerve atrophy. Electroretinography (ERG) was normal. At 5 years of age, an extinguished ERG was found, and retinitis pigmentosa with optic nerve atrophy and hypermetropia were found on ophthalmoscopic examination. At the age of 2 months she started to have frequent episodes of fever of undetermined origin, during which she was comatose twice and once had a seizure. Hypernatremia (150--160 mval) and hyperchloremia (112--120 mval) together with a low specific gravity of urine (1002--1014) were constant findings. At the age of 7 years she was admitted to our hospital and was found to be grossly retarded and hypotonic with a developmental age of 2 years, an overweight of 3000 g (90th percentile according to length), length of 108 em (below 3rd percentile for age) and mierocephaly (below 3rd percentile for age). She had coxa valga antetorsa and talus vertiealis. Blood smear, BUN and serum creatinine
60
P. Koepp Body
~
~mperature 4039. 37 Chloride mval Serum
120. 110. 10090-
Spec. Gravity 1020. Urine 1010-
daily fluid intake - -
2000 m!
I - - 9 0 0 - 700 ml
*
normal Sod. restricted diet diet I I7 1-50.-{-1200--~ mval / day cal Pitressin
DDAVP Qlml
5 IE ira.
25. Jan.
l ~ Feb.
10.
15
20.
25.
1. March. 1975
~ig. l. Body temperature, specific gravity of urine, serum chloride concentration and fluid intake of a patient with Laurenee-Moon-Biedl syndrome with diabetes insipidus neurohormonalis before and after treatment with DDAVP
were normal, but serum sodium and serum chloride concentrations were increased (150--163 and 107--121 royal, respectively). Urine osmolarity was low (80 mosmol) and serum osmolarity was increased (330 mosmol, normal 275--295 mosmol) (Fig. 1). Intravenous pyelography showed hypoplastic kidneys; biopsy revealed glomerular dysplasia histologically. Special Investigations A water deprivation test was performed; there was only a slight rise in urine osmolarity while the patient lost more than 5~ of b o d y weight, but she became somnolent and the test was discontinued. A vasopressin test was performed thereafter (Fig. 2). A rise of urine osmolarity from 50 to 410 mosmol and normalization of serum osmolarity (330 mosmol before and 290 mosmol 60 min after injection of 5 I E Pitressin | intravenously) disclosed vasopressin sensitive diabetes insipidus. Treatment was successful with a new synthetic vasopressin analogue, D D A V P (1-deamino-8-D-arginine vasopressin) (Aronson et al., 1973) (Fig. 1).
Laurence-Moon-Biedl Syndrome URINE
61
5 IE PITRE$SIN Lv, [ (aqueous solution)
OSMOLARITY [m osmoI]
_! 356 250.
15C
56 TIME
SERUM OSMOLARITY
[m osmol]
336 310 290
--yj
270
Fig. 2. Serum and urine osmolarity during vasopressin test in a patient with Laurence-MoonBiedl syndrome with diabetes insipidus neurohormonalis
Discussion
Of the characteristic features of the LMB syndrome, our patient lacked the polydactyly and hypogenitalism could not be demonstrated in the female infant. But she also displayed several unusual features: diabetes insipidus neurohormohalls, small stature and a renal disorder. The association of LMB syndrome with diabetes insipidus neurohormonalis has been reported occasionally (Krill et al., 1961; Warkany et al., 1937). In our patient the endocrine abnormality was not diagnosed until the 6th year of age. Since hypernatremia b y itself is a handicap to the development and function of the brain (Cooke and Ottenheimer, 1960), untreated diabetes insipidus neurohormonalis might well have contributed to some degree of the cerebral damage in our patient. Small stature was one of the symptoms of Biedl's patients (Biedl, 1922) but has rarely been reported thereafter (Warkany et al., 1937). The diabetes insipidus neurohormonalis might also have contributed to this manifestation. Renal disorders are of special importance for patients with LMB syndrome since they are found in almost all postmortem examinations (Bauman and Hogan, 1973) and they are a frequent cause of death in these patients (Alton and McDonald, 1973). Consequently intravenous pyelography and possibly renal histology should
62
P. Koepp
be p e r f o r m e d in all L M B p a t i e n t s in o r d e r t o disclose t h e r e n a l disorder, which t h e n m i g h t be successfully t r e a t e d a n d f u r t h e r d a m a g e p r e v e n t e d .
References Alton, D. J., McDonald, P. : Urographie findings in the Bardet-Biedl syndrome. Radiology 109, 659 (1973) Aronson, A. S., Andersson, K.-E., Bergstrand, C. G., Mulder, J. L. : Treatment of diabetes insipidus in children with DDAVP, a new synthetic analogue of vasoloressin. Acta 9aediat. stand. 62, 133 (1973) Bauman, M. L., Hogan, G. R.: Laurence-Moon-Biedl syndrome. Amer. J. Dis. Child. 126, 119 (1973) Biedl, A. : Ein Geschwisterpaar mit adiposogenitaler Dystrophie. D~seh. reed. Wsehr. 48, 1630 (1922) Cooke, R. E., Ottenheimer, E. J. : Clinical and experimental interrelations of sodium and the central nervous system. Advanc. Pediar XI, 81 (1960) Klein, D., Ammann, F.: The syndrome of Laurence-Moon-Biedl and allied diseases in Switzerland. J. neurol. Sci. 9, 479 (1969) Krill, A. E., Folk, E., Rosenthal, I. M.: Electroretinography in the Laurence-Moon-Biedl syndrome. Amer. J. Dis. Child. 102, 205 (1961) Warkany, J., Frauenberger, G. S., Mitchell, A. G. : Heredofamilial deviations: The LaurenceMoomBiedl synch'ome. Amer. J. Dis. Child. 53, 455 (1937) Dr. P. Koepp Universit~ts-Kinderklinik D-2000 Hamburg 20, MartinistraBe 52 Federal Republic of Germany
