Breitmeyer, T., Julesz, B., tiropfl, W. (1975) ‘Dynamic random-dot stereograms reveal updown anisotropy and left-right isotropy between cortical hemifields.’ Science, 187, 269-270. Catalano, R . A . , Trivisani, M. G., Simon, J . W. (1990) ‘Functional eyelid pulling in children.’ Americun Journal of Ophthalmology, 11 0, 300-302. Cummings, M . L., van Hof-van Duin, J., Mayer, D. L., Hansen, R . M . , Fulton, A. B. (1988) ‘Visual fields of young children.’ Behavioural Brain Research, 29, 7-16. Curcio, C. A , , Sloan, ti. R., Kalina, R . E., Hendrickson, A. E. (1990) ‘Human photoreceptor topography.’ Journal of Comparairve Neurology, 292. 497-523. Dell’Osso, L. F., Daroff, M. D. (1975) ‘Congenital nystagmus wave forms and foveation strategy.’ Docurnenia Ophihalomogicu, 39, 155-182. Good, W . V., Hoyt, C. S. (1989) ‘Behavioral correlates of poor vision in children.’ Iniernational Ophihalmology Clinics, 29, 57-60. Jacob5, L., Heffner, R . R . , Newman, N. (1984) ‘Selective paralysis of downward gaze caused by bilateral lesion of the periaqueductal gray commisure of the superior colliculi.’ Neurology, 34 (Suppl.), 95. (Absiraci.) Jampolsky, A . (1978) ‘Unequal visual inputs and
strabismus management: a comparison of human and animal strabismus.’ I n Helveston, E. M. (Ed.) Symposium on Strabismus, Transactions of [he New Orleans Academy of Ophihaltnolog-v. St. Louis: C . V . Mosby. p. 434. Jan, J . E., Freeman, R . D., McCormick, A . Q., Scott, E. P . , Robertson, W. D . , Newman, D. E. (1983) ‘Eye pressing by visually impaired children ,’ Developmental Medicine and Child Neurolog.v, 25, 75 5-762. - Farrell, ti., Wong, P . K., McCormick, A . Q . (1986) ‘Eye and head movements of visually impaired children.’ Developmenial Medicine and Child Neurology, 28, 285-293. - Grocnveld, M . , Sykanda, A . M., Hoyt, C. S. (1987) ‘Behavioural characteristics of children with permanent cortical visual impairment.’ Developmenial Medicine and Child Neurology, 29, 571-576. Mets, M. (1990) ‘Tonic upgaze in infancy.’ Archives of Ophihalmology, 108, 482-483. Nakayama, ti., Tyler, C. W., Appelman, J . (1977) ‘A new angle o n the vertical horopter.’ In vesti,putive Ophihalmology and Visual Sciences, 16, 82. Taylor, D., Lake, B. D., Stephens, R . (1983) ‘Neurolipidoses.’ I n Wybar, t i . , Taylor, D. (Eds.) Pediatric Ophihalmology, Curreni Aspecis. New York: Marcel Dekker. pp. 180-181.
Fami I i a I ParoxysmaI Rhabdomyolysi s Managemen- of Two Cases of the Non-exerti ona Type
attacks (Bowden et al. 1956, Korein et al. 1959, Favara et al. 1967, Savage el al. 1971). The pathogenesis is unknown, in contrast to our increasing understanding of rhabdomyolysis following exercise (McArdle 1951, Tarui et af. 1965, DiMauro and DiMauro 1973, Bank et al. 1975, DiMauro et al. 1981, Bresolin et at. 1987). We describe two affected families and suggest guidelines for management of the condition.
~
V. Ramesh D. Gardner-Medwin
Familial paroxysmal rhabdomyolysis is a rare but distinctive clinical entity which results in life-threatening episodes of muscular paralysis, myoglobinuria and renal failure. It occurs in young children, usually under the age of five; their siblings of either sex may be affected, suggesting an autosomal recessive mode of inheritance. The attacks have no relation to exercise. In susceptible children, intercurrent illnesses, commonly upper respiratory-tract infections, trigger the
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6
Case reports CASE 1 C.S. was a 33-month-old girl referred in 1981, three months after a single attack of rhabdomyolysis. At the time she had been suffering for two months from pertussis; her appetitie was poor and she had vomited for two days before the rhabdomyolysis occurred. During the attack she developed weakness of all four limbs, lost the ability to walk and passed reddish-brown urine over a period of 24 hours. O n admission to another hospital she was afebrile, hypotonic and drowsy, with moderate muscle weakness and reduced tendon reflexes. Neurological examination was otherwise normal. A convulsion o n the day of admission did not recur and her subsequent EEG was normal. There was heavy proteinuria, and urine microscopy showed red cells and occasional granular casts.
73
v1
Case 1 23Y
0-p
26Y
Case 2 28y
[7 unaffected
O
F
32y
paroxysmal myoglobinuria
Fig. 1. Pedigree of cases I and 2.
74
Large amounts of myoglobin were detected on cellulose acetate electrophoresis of the urine. Blood urine and electrolytes were normal and serum calcium was 2.35mmol/L. Her serum creatine kinase (CK) was measured at 175,OOOU/L three days after the onset of her attack, but fell to 400 U/L by the 10th day. She was bedridden for three weeks, after which she made a gradual and complete recovery. When seen by us she was completely asymptomatic and normal on examination. Her older brother had died suddenly at the age of four years following a day’s illness with cough, wheezing, vomiting and reddish-brown discoloration of his urine. Just before his death he had a large ‘coffee-grounds’ vomit and was thought to have aspirated the vomitus. The postmortem diagnosis was severe bronchial asthma; his muscles were not examined. At three years of age, investigations after the first of several attacks of reddish discoloration of urine during the course of upper respiratory-tract infections had been unremarkable; the attacks were dismissed as unexplained haemoglobinuria. There was one unaffected sibling. The parents were not consanguineous (Fig. 1). Initial investigations, including blood urea, electrolytes and urine analysis, were normal. Her resting CK was 721U/L. A left quadriceps muscle biopsy was obtained under general anaesthesia, with special precautions against malignant hyperpyrexia. The muscle histology was largely normal, with occasional scattered, angulated, atrophic fibres of both types 1 and 2 and with an increase in type 2c
intermediate fibres. There was a minimal excess o f neutral fat in some type 1 fibres. Measured carnitine palmitoyl transferase activity was normal and there was no histochemical evidence of a mitochondria1 disorder. During and after biopsy, C.S. had received a 5 per cent dextrose infusion, giving her 1 .9mg/kg/hour of glucose. After the biopsy she was drowsy and irritable and developed myoglobinuria. Her serum CK rose to 43,4OOlU/L (up to 140U/L). Her urine was alkalinised with 2mmol/kg of 8 . 4 per cent sodium bicarbonate as a continuous infusion. There was no disturbance of renal or respiratory function. She made a complete recovery over the next two days. She was discharged home with advice to avoid fasting for periods longer than eight hours, to take high-energy drinks during intercurrent illnesses, and to arrange hospital admission for administration of intravenous fluids should oral intake become difficult. Dantrolene sodium was recommended empirically at a dose of lmg/kg, six-hourly, for a period of 48 hours (not exceeding IOmg/kg total dose) if an attack of rhabdomyolysis should occur. Follow-up enquiries eight years later revealed that she had had one more episode of rhabdomyolysis after an 18-hour fast at five years of age, but none since. CASE 2 M.N. was a 22-month-old girl referred from Kuwait for futher investigation after a single life-threatening episode of rhabdomyolysis, with myoglobinuria and renal tubular necrosis, at the age of 18 months. She was the fourth of five children of a Bedouin couple who were first-cousins. Two older sisters had died at about five years of age during attacks of acute generalised muscle weakness and rhabdomyolysis. One had presented initially at three years of age with acute, transient, generalised muscle weakness, hyporeflexia and myoglobinuria; her serum CK was 91,644UlL. TWO more attacks had followed over the course of the subsequent two years, the final attack ending fatally at home within a few hours of onset. The second sister presented for the first time at five years of age with an identical illness (anorexia, generalised muscular weakness, myoglobinuria, elevated muscle enzymes), and died within two hours of hospital admission. There had been exercise intolerance or attacks following exertion in either case. Of the surviving children, an older brother aged four years was apparently unaffected and a younger sister aged 17 months had an attack of muscular weakness and had passed dark urine at 11 months of age in the course of an upper respiratory-tract infection (Fig. 1). M.N. was an active child, with no history of previous illness or exertional intolerance. Her first attack of muscle weakness with myoglobinuria followed an upper respiratory-tract infection, with fever and three days of anorexia. Muscle weakness began in her lower limbs, and over a few hours became generalised. Her urine was dark brown and contained protein, myoglobin and 18 to 20 red cells per high-power field, but no casts. Serum CK reached a maximum value of 24,00OU/L. She developed acute tubular necrosis and needed several weeks in hospital to make a complete recovery.
TABLE 1 Blood levels of intermediary metabolites, glucose and CK for case 2 (16-hour fast during 2030 to 1230hrs)*
Time (hrs)
Lac
2030 0830 1015 1215 I400
1.4 1.07 1.26 1.65
Pyr
poh
AcAc
Gly
Alu
Gluc
FFA
CK
-
IQI
W
ri
QI
2
1.80
0.16 0.09 0.09 0.12 0.14
0.11
2.13 3.50 3.27 3.70
strabismus management: a comparison of human and animal strabismus.’ I n Helveston, E. M. (Ed.) Symposium on Strabismus, Transactions of [he New Orleans Academy of Ophihaltnolog-v. St. Louis: C . V . Mosby. p. 434. Jan, J . E., Freeman, R . D., McCormick, A . Q., Scott, E. P . , Robertson, W. D . , Newman, D. E. (1983) ‘Eye pressing by visually impaired children ,’ Developmental Medicine and Child Neurolog.v, 25, 75 5-762. - Farrell, ti., Wong, P . K., McCormick, A . Q . (1986) ‘Eye and head movements of visually impaired children.’ Developmenial Medicine and Child Neurology, 28, 285-293. - Grocnveld, M . , Sykanda, A . M., Hoyt, C. S. (1987) ‘Behavioural characteristics of children with permanent cortical visual impairment.’ Developmenial Medicine and Child Neurology, 29, 571-576. Mets, M. (1990) ‘Tonic upgaze in infancy.’ Archives of Ophihalmology, 108, 482-483. Nakayama, ti., Tyler, C. W., Appelman, J . (1977) ‘A new angle o n the vertical horopter.’ In vesti,putive Ophihalmology and Visual Sciences, 16, 82. Taylor, D., Lake, B. D., Stephens, R . (1983) ‘Neurolipidoses.’ I n Wybar, t i . , Taylor, D. (Eds.) Pediatric Ophihalmology, Curreni Aspecis. New York: Marcel Dekker. pp. 180-181.
Fami I i a I ParoxysmaI Rhabdomyolysi s Managemen- of Two Cases of the Non-exerti ona Type
attacks (Bowden et al. 1956, Korein et al. 1959, Favara et al. 1967, Savage el al. 1971). The pathogenesis is unknown, in contrast to our increasing understanding of rhabdomyolysis following exercise (McArdle 1951, Tarui et af. 1965, DiMauro and DiMauro 1973, Bank et al. 1975, DiMauro et al. 1981, Bresolin et at. 1987). We describe two affected families and suggest guidelines for management of the condition.
~
V. Ramesh D. Gardner-Medwin
Familial paroxysmal rhabdomyolysis is a rare but distinctive clinical entity which results in life-threatening episodes of muscular paralysis, myoglobinuria and renal failure. It occurs in young children, usually under the age of five; their siblings of either sex may be affected, suggesting an autosomal recessive mode of inheritance. The attacks have no relation to exercise. In susceptible children, intercurrent illnesses, commonly upper respiratory-tract infections, trigger the
m N
Q‘
-2
...
c
f
$ a
6
Case reports CASE 1 C.S. was a 33-month-old girl referred in 1981, three months after a single attack of rhabdomyolysis. At the time she had been suffering for two months from pertussis; her appetitie was poor and she had vomited for two days before the rhabdomyolysis occurred. During the attack she developed weakness of all four limbs, lost the ability to walk and passed reddish-brown urine over a period of 24 hours. O n admission to another hospital she was afebrile, hypotonic and drowsy, with moderate muscle weakness and reduced tendon reflexes. Neurological examination was otherwise normal. A convulsion o n the day of admission did not recur and her subsequent EEG was normal. There was heavy proteinuria, and urine microscopy showed red cells and occasional granular casts.
73
v1
Case 1 23Y
0-p
26Y
Case 2 28y
[7 unaffected
O
F
32y
paroxysmal myoglobinuria
Fig. 1. Pedigree of cases I and 2.
74
Large amounts of myoglobin were detected on cellulose acetate electrophoresis of the urine. Blood urine and electrolytes were normal and serum calcium was 2.35mmol/L. Her serum creatine kinase (CK) was measured at 175,OOOU/L three days after the onset of her attack, but fell to 400 U/L by the 10th day. She was bedridden for three weeks, after which she made a gradual and complete recovery. When seen by us she was completely asymptomatic and normal on examination. Her older brother had died suddenly at the age of four years following a day’s illness with cough, wheezing, vomiting and reddish-brown discoloration of his urine. Just before his death he had a large ‘coffee-grounds’ vomit and was thought to have aspirated the vomitus. The postmortem diagnosis was severe bronchial asthma; his muscles were not examined. At three years of age, investigations after the first of several attacks of reddish discoloration of urine during the course of upper respiratory-tract infections had been unremarkable; the attacks were dismissed as unexplained haemoglobinuria. There was one unaffected sibling. The parents were not consanguineous (Fig. 1). Initial investigations, including blood urea, electrolytes and urine analysis, were normal. Her resting CK was 721U/L. A left quadriceps muscle biopsy was obtained under general anaesthesia, with special precautions against malignant hyperpyrexia. The muscle histology was largely normal, with occasional scattered, angulated, atrophic fibres of both types 1 and 2 and with an increase in type 2c
intermediate fibres. There was a minimal excess o f neutral fat in some type 1 fibres. Measured carnitine palmitoyl transferase activity was normal and there was no histochemical evidence of a mitochondria1 disorder. During and after biopsy, C.S. had received a 5 per cent dextrose infusion, giving her 1 .9mg/kg/hour of glucose. After the biopsy she was drowsy and irritable and developed myoglobinuria. Her serum CK rose to 43,4OOlU/L (up to 140U/L). Her urine was alkalinised with 2mmol/kg of 8 . 4 per cent sodium bicarbonate as a continuous infusion. There was no disturbance of renal or respiratory function. She made a complete recovery over the next two days. She was discharged home with advice to avoid fasting for periods longer than eight hours, to take high-energy drinks during intercurrent illnesses, and to arrange hospital admission for administration of intravenous fluids should oral intake become difficult. Dantrolene sodium was recommended empirically at a dose of lmg/kg, six-hourly, for a period of 48 hours (not exceeding IOmg/kg total dose) if an attack of rhabdomyolysis should occur. Follow-up enquiries eight years later revealed that she had had one more episode of rhabdomyolysis after an 18-hour fast at five years of age, but none since. CASE 2 M.N. was a 22-month-old girl referred from Kuwait for futher investigation after a single life-threatening episode of rhabdomyolysis, with myoglobinuria and renal tubular necrosis, at the age of 18 months. She was the fourth of five children of a Bedouin couple who were first-cousins. Two older sisters had died at about five years of age during attacks of acute generalised muscle weakness and rhabdomyolysis. One had presented initially at three years of age with acute, transient, generalised muscle weakness, hyporeflexia and myoglobinuria; her serum CK was 91,644UlL. TWO more attacks had followed over the course of the subsequent two years, the final attack ending fatally at home within a few hours of onset. The second sister presented for the first time at five years of age with an identical illness (anorexia, generalised muscular weakness, myoglobinuria, elevated muscle enzymes), and died within two hours of hospital admission. There had been exercise intolerance or attacks following exertion in either case. Of the surviving children, an older brother aged four years was apparently unaffected and a younger sister aged 17 months had an attack of muscular weakness and had passed dark urine at 11 months of age in the course of an upper respiratory-tract infection (Fig. 1). M.N. was an active child, with no history of previous illness or exertional intolerance. Her first attack of muscle weakness with myoglobinuria followed an upper respiratory-tract infection, with fever and three days of anorexia. Muscle weakness began in her lower limbs, and over a few hours became generalised. Her urine was dark brown and contained protein, myoglobin and 18 to 20 red cells per high-power field, but no casts. Serum CK reached a maximum value of 24,00OU/L. She developed acute tubular necrosis and needed several weeks in hospital to make a complete recovery.
TABLE 1 Blood levels of intermediary metabolites, glucose and CK for case 2 (16-hour fast during 2030 to 1230hrs)*
Time (hrs)
Lac
2030 0830 1015 1215 I400
1.4 1.07 1.26 1.65
Pyr
poh
AcAc
Gly
Alu
Gluc
FFA
CK
-
IQI
W
ri
QI
2
1.80
0.16 0.09 0.09 0.12 0.14
0.11
2.13 3.50 3.27 3.70
