- Email: [email protected]
LEBER'S HEREDITARY OPTIC NEURORETINOPATHY, A MITOCHONDRIAL DISEASE?
1474 final period (May 14-June 30) there were no isolations from fifty umbilical stumps. Evidently umbilical s were the reservoir of infection as shown in previous Neonatal group-A streptococcal septicaemia should be taken as a warning of colonisation of the nursery. It may be useful to carry out routine bacteriological studies of umbilical stumps to help prevent outbreaks of neonatal septicaemia.
stumps studies.,3
Department of Medical Microbiology, University of Turku,
O.-P. LEHTONEN
Department of Paediatrics, Turku University Central Hospital
OLLI RUUSKANEN PENTTI KERO OUTI HOLLO
Department of Obstetrics and Gynaecology, Turku University Central Hospital
RISTO ERKKOLA TUULA SALMI
2
3.
Isenberg HD, Tucci V, Lipsitz P, Facklam RR. Clinical laboratory and epidemiological investigations of a Streptococcus pyogenes cluster epidemic in a newborn nursery J Clin Microbiol 1984; 19: 366-70 Geil CC, Castle WK, Mortimer EA. Group A streptococcal infections in newborn nurseries Pediatrics 1970; 46: 849-54. Nelson JD, Dillon HC, Howard JB. A prolonged nursery epidemic associated with a newly recognized type of group A streptococcus. J Pediatr 1976; 89: 792-96.
ORAL REHYDRATION FOR LOW BIRTH WEIGHT BABY WITH DIARRHOEA
SIR,-In response I would like to trial in 65 infants
818)
to
Dr Abdalla and
draw attention
colleagues’ study (Oct 6,
to our
p
controlled, randomised
aged 0-3 months, of whom 23 were lowbirthweight (LBW) babies. We compared the efficacy and safety of the standard WHO oral glucose electrolyte solution containing 90 mmol sodium/1 (group A: 22 infants, 8 LBW) with that of an oral glucose-electrolyte solution containing 60 mmol sodium/1 (group B: 22 infants, 8 LBW) and with standard intravenous therapy (group C: 21 infants, 7 LBW). The glucose electrolyte solution containing 60 mmol sodium proved to be as safe and effective as intravenous rehydration, while the standard WHO solution carried a significant risk of excessive sodium retention, especially in LBW neonates. The excessive sodium retention resulted in hypernatraemia (50%), periorbital oedema (50%), mild pedal oedema (27%), excessive irritability, and convulsions (4-5%). The corresponding percentages for group A LBW neonates were 63%, 63%, 38%, and 13%. Our observations are at marked variance from Abdalla and colleagues’, wherein only 2 neonates (9 - 5%) exhibited transient asymptomatic hypernatraemia with the WHO formulation. These differences are difficult to explain. However, we need clarification of whether, during the rehydration period, adequate free water intake was ensured (as in the study2 that encouraged them to undertake their trial) and whether rehydration solution was used to replace stool losses in the maintenance period. Until this issue is resolved it would seem prudent to avoid the use of WHO rehydration solution alone in LBW neonates. Alternatives would be a solution containing less sodium (60 mmol/1) or adequate free water intake in a supervised manner if the WHO solution is used. In most babies (25/28) Abdalla et al used lactose-free soy-based formula for refeeding. Except for the occasional infant who has evidence of lactose intolerance, the use of such an expensive diet is to be discouraged. Not only does this delay the establishment of a normal feeding pattern but also it may create a mistaken belief that it is a "treatment diet". In our experience, breast milk and/or half diluted cow’s milk is satisfactory for early refeeding in LBW babies. Department of Paediatrics, Safdarjung Hospital, New Delhi-110029, India 1.
H. P.S. SACHDEV
Bhargava SK, Sachdev HPS, Das Gupta B, Daral TS, Singh HP, Man Mohan. Oral rehydration of neonates and young infants with dehydrating diarrhoea. Comparison of low and standard sodium content in oral rehydration solutions J Pediatr Gastroenterol Nuti 1984; 3: 500-05 D, Posada G, Mata L Treatment of 242 neonates with dehydrating diarrhoea with an oral glucose electrolyte solution J Pediatr 1983, 102: 153-56
2 Pizzaro
SIR,-Leber’s hereditary optic neuroretinopathy is characterised
by visual loss in otherwise healthy young men. The loss is usually permanent with severe bilateral optic atrophy and large absolute centrocecal scotomas. Only 14% of affected subjects are women. Female carriers can transmit the disease to their sons and the carrier their daughters, whereas men are not known to transmit the disease. The mechanism of this peculiar inheritance pattern is 1 unknown, but mitochondrial inheritance has been suggested. Since the mitochondrial DNA of the fetus is derived almost exclusively from the mother, a non-mendelian pattern of inheritance might be predicted in disorders primarily affecting the mitochondrial genome, although the male predominance in the patient population would remain unexplained. state to
SF-20520 Turku 52, Finland
1
LEBER’S HEREDITARY OPTIC NEURORETINOPATHY, A MITOCHONDRIAL DISEASE?
The pathogenesis of Leber’s disease is unknown but a flaw in cyanide metabolism has been suggested. Cagianut et al2 reported a pronounced reduction in the activity of the enzyme thiosulphatesulphur transferase (rhodanese) in liver samples from two Leber patients. This mitochondrial matrix enzyme detoxifies cyanide by a reaction with thiosulphate to form thiocyanate and sulphite. The evidence suggesting a mitochondrial defect prompted us to study mitochondrial structure and rhodanese activity in Leber’s disease. Many mitochondrial disorders, including some cerebral syndromes,3,4 are expressed as structural changes in skeletal muscle mitochondria, even when there is no clinically manifest myopathy. We therefore chose to use skeletal muscle as an easily obtainable source of mitochondria. We took biopsy samples by the semi-open conchotome method from the anterior tibial muscle of 13 affected males and 9 normal male volunteers; part of the specimen was frozen for biochemical studies and histochemistry and another part was processed for electron microscopy. The muscle rhodanese activity was determined by a modification of the method ofSörbo5and is expressed in nmol per min per mg of protein. In the 13 affected males the activity was 865±231 (mean±SD) and in the controls (n = 8) 788-t 197; the difference is not significant (t test). Electron micrographs of the subsarcolemmal collections of mitochondria were assessed subjectively without knowledge of the diagnosis. In 8 of the 13 patients the mitochondria were considered unusually large (though not otherwise remarkable), whereas in only 1 of the 9 controls was any of the subsarcolemmal collections thought to include unusually large mitochondria (p=0 016, Fisher’s test). When the subsarcolemmal mitochondrial profiles were analysed planimetrically, the pooled profile areas were significantly larger in the Leber group than in the control group (p<0 01, Kolmogorov-Smirnov test). In contrast, the mitochondria in the intermyofibrillar area appeared to be of normal size, and their volume fractions as determined by point-counting morphometry were similar in the Leber and control samples.
This study did not confirm the reported low activity of rhodanese in Leber On the other hand, it is possible that the subsarcolemmal mitochondria are enlarged in Leber’s disease as a compensation for an as yet unknown metabolic defect. Further studies on the mitochondrial function are therefore required.
patients.2
Departments of Ophthalmology, Pathology, and Clinical Neurophysiology, University of Turku SF-20520 Turku 52, Finland, and Department of Medical Biochemistry, University of Oulu
E. NIKOSKELAINEN I. E. HASSINEN L. PALJARVI H. LANG H. KALIMO
1 Egger J, Wilson J Mitochondrial inheritance in a mitochondrially mediated disease. N 1983, 309: 142-46. Engl Med J 2. Cagianut B, Rhyner K, Furrer W, Schnebh HP Thiosulphate-sulphur transferase (rhodanese) deficiency in Leber’s hereditary optic atrophy. Lancet 1981, ii: 981-82. 3. Tassin S, Brucher JM The mitochondrial disorders pathogenesis and aetiological classification. Neuropathol Appl Neurobiol 1982; 8: 251-63. 4. Morgan-Hughes JA, Hayes DJ, Clark JB, et al. Mitochondrial encephalomyelopathies. Biochemical studies in two cases revealing defects in the respiratory chain. Brain 1982, 105: 553-82 5. Sörbo BH Rhodanese In: Colowick SP, Kaplan NO, eds. Methods Vol II. New York Academic Press, 1955. 334-37
of enzymology.
stumps studies.,3
Department of Medical Microbiology, University of Turku,
O.-P. LEHTONEN
Department of Paediatrics, Turku University Central Hospital
OLLI RUUSKANEN PENTTI KERO OUTI HOLLO
Department of Obstetrics and Gynaecology, Turku University Central Hospital
RISTO ERKKOLA TUULA SALMI
2
3.
Isenberg HD, Tucci V, Lipsitz P, Facklam RR. Clinical laboratory and epidemiological investigations of a Streptococcus pyogenes cluster epidemic in a newborn nursery J Clin Microbiol 1984; 19: 366-70 Geil CC, Castle WK, Mortimer EA. Group A streptococcal infections in newborn nurseries Pediatrics 1970; 46: 849-54. Nelson JD, Dillon HC, Howard JB. A prolonged nursery epidemic associated with a newly recognized type of group A streptococcus. J Pediatr 1976; 89: 792-96.
ORAL REHYDRATION FOR LOW BIRTH WEIGHT BABY WITH DIARRHOEA
SIR,-In response I would like to trial in 65 infants
818)
to
Dr Abdalla and
draw attention
colleagues’ study (Oct 6,
to our
p
controlled, randomised
aged 0-3 months, of whom 23 were lowbirthweight (LBW) babies. We compared the efficacy and safety of the standard WHO oral glucose electrolyte solution containing 90 mmol sodium/1 (group A: 22 infants, 8 LBW) with that of an oral glucose-electrolyte solution containing 60 mmol sodium/1 (group B: 22 infants, 8 LBW) and with standard intravenous therapy (group C: 21 infants, 7 LBW). The glucose electrolyte solution containing 60 mmol sodium proved to be as safe and effective as intravenous rehydration, while the standard WHO solution carried a significant risk of excessive sodium retention, especially in LBW neonates. The excessive sodium retention resulted in hypernatraemia (50%), periorbital oedema (50%), mild pedal oedema (27%), excessive irritability, and convulsions (4-5%). The corresponding percentages for group A LBW neonates were 63%, 63%, 38%, and 13%. Our observations are at marked variance from Abdalla and colleagues’, wherein only 2 neonates (9 - 5%) exhibited transient asymptomatic hypernatraemia with the WHO formulation. These differences are difficult to explain. However, we need clarification of whether, during the rehydration period, adequate free water intake was ensured (as in the study2 that encouraged them to undertake their trial) and whether rehydration solution was used to replace stool losses in the maintenance period. Until this issue is resolved it would seem prudent to avoid the use of WHO rehydration solution alone in LBW neonates. Alternatives would be a solution containing less sodium (60 mmol/1) or adequate free water intake in a supervised manner if the WHO solution is used. In most babies (25/28) Abdalla et al used lactose-free soy-based formula for refeeding. Except for the occasional infant who has evidence of lactose intolerance, the use of such an expensive diet is to be discouraged. Not only does this delay the establishment of a normal feeding pattern but also it may create a mistaken belief that it is a "treatment diet". In our experience, breast milk and/or half diluted cow’s milk is satisfactory for early refeeding in LBW babies. Department of Paediatrics, Safdarjung Hospital, New Delhi-110029, India 1.
H. P.S. SACHDEV
Bhargava SK, Sachdev HPS, Das Gupta B, Daral TS, Singh HP, Man Mohan. Oral rehydration of neonates and young infants with dehydrating diarrhoea. Comparison of low and standard sodium content in oral rehydration solutions J Pediatr Gastroenterol Nuti 1984; 3: 500-05 D, Posada G, Mata L Treatment of 242 neonates with dehydrating diarrhoea with an oral glucose electrolyte solution J Pediatr 1983, 102: 153-56
2 Pizzaro
SIR,-Leber’s hereditary optic neuroretinopathy is characterised
by visual loss in otherwise healthy young men. The loss is usually permanent with severe bilateral optic atrophy and large absolute centrocecal scotomas. Only 14% of affected subjects are women. Female carriers can transmit the disease to their sons and the carrier their daughters, whereas men are not known to transmit the disease. The mechanism of this peculiar inheritance pattern is 1 unknown, but mitochondrial inheritance has been suggested. Since the mitochondrial DNA of the fetus is derived almost exclusively from the mother, a non-mendelian pattern of inheritance might be predicted in disorders primarily affecting the mitochondrial genome, although the male predominance in the patient population would remain unexplained. state to
SF-20520 Turku 52, Finland
1
LEBER’S HEREDITARY OPTIC NEURORETINOPATHY, A MITOCHONDRIAL DISEASE?
The pathogenesis of Leber’s disease is unknown but a flaw in cyanide metabolism has been suggested. Cagianut et al2 reported a pronounced reduction in the activity of the enzyme thiosulphatesulphur transferase (rhodanese) in liver samples from two Leber patients. This mitochondrial matrix enzyme detoxifies cyanide by a reaction with thiosulphate to form thiocyanate and sulphite. The evidence suggesting a mitochondrial defect prompted us to study mitochondrial structure and rhodanese activity in Leber’s disease. Many mitochondrial disorders, including some cerebral syndromes,3,4 are expressed as structural changes in skeletal muscle mitochondria, even when there is no clinically manifest myopathy. We therefore chose to use skeletal muscle as an easily obtainable source of mitochondria. We took biopsy samples by the semi-open conchotome method from the anterior tibial muscle of 13 affected males and 9 normal male volunteers; part of the specimen was frozen for biochemical studies and histochemistry and another part was processed for electron microscopy. The muscle rhodanese activity was determined by a modification of the method ofSörbo5and is expressed in nmol per min per mg of protein. In the 13 affected males the activity was 865±231 (mean±SD) and in the controls (n = 8) 788-t 197; the difference is not significant (t test). Electron micrographs of the subsarcolemmal collections of mitochondria were assessed subjectively without knowledge of the diagnosis. In 8 of the 13 patients the mitochondria were considered unusually large (though not otherwise remarkable), whereas in only 1 of the 9 controls was any of the subsarcolemmal collections thought to include unusually large mitochondria (p=0 016, Fisher’s test). When the subsarcolemmal mitochondrial profiles were analysed planimetrically, the pooled profile areas were significantly larger in the Leber group than in the control group (p<0 01, Kolmogorov-Smirnov test). In contrast, the mitochondria in the intermyofibrillar area appeared to be of normal size, and their volume fractions as determined by point-counting morphometry were similar in the Leber and control samples.
This study did not confirm the reported low activity of rhodanese in Leber On the other hand, it is possible that the subsarcolemmal mitochondria are enlarged in Leber’s disease as a compensation for an as yet unknown metabolic defect. Further studies on the mitochondrial function are therefore required.
patients.2
Departments of Ophthalmology, Pathology, and Clinical Neurophysiology, University of Turku SF-20520 Turku 52, Finland, and Department of Medical Biochemistry, University of Oulu
E. NIKOSKELAINEN I. E. HASSINEN L. PALJARVI H. LANG H. KALIMO
1 Egger J, Wilson J Mitochondrial inheritance in a mitochondrially mediated disease. N 1983, 309: 142-46. Engl Med J 2. Cagianut B, Rhyner K, Furrer W, Schnebh HP Thiosulphate-sulphur transferase (rhodanese) deficiency in Leber’s hereditary optic atrophy. Lancet 1981, ii: 981-82. 3. Tassin S, Brucher JM The mitochondrial disorders pathogenesis and aetiological classification. Neuropathol Appl Neurobiol 1982; 8: 251-63. 4. Morgan-Hughes JA, Hayes DJ, Clark JB, et al. Mitochondrial encephalomyelopathies. Biochemical studies in two cases revealing defects in the respiratory chain. Brain 1982, 105: 553-82 5. Sörbo BH Rhodanese In: Colowick SP, Kaplan NO, eds. Methods Vol II. New York Academic Press, 1955. 334-37
of enzymology.