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The N-syndrome. A “new” multiple congenital anomaly-mental retardation syndrome
920
Abstracts
dysplasia (BPD), in general, the need for oxygen concentration of 60 per cent or more was of shorter duration in infants who received IPPV with PEEP than in those with IPPV alone. Since prolonged duration of high inspired oxygen concentration is known to induce BPD, the authors attributed the lower incidence of BPD in the IPPV plus PEEP group to this fact.
32. Biliary cholestasis associated with peripheral administration of L-amino acids and dextrose M. Zarif,* D. Vidyasagar, P. B. Szanto,* and R. S. Pildes, Chicago, Ill, A modified form of parenteral alimentation (dextrose, 10 per cent and synthetic L-amino acids, protein 1.7 to 3.4 gin. per cent) has been used extensively in our nursery for low-birth-weight infants who required prolonged assisted ventilation or who were unable to tolerate oral feedings. Biliary cholestasis was diagnosed at autopsy in four infants who received modified alimentation and in a fifth infant who received total p~enteral alimentation (dextrose 20 per cent, L-amino acids 3.8 per cent) via a central venous catheter. All five infants weighed tess than 1,250 grams at birth (range, 943 to 1,247 grams), were appropriate for their gestational age and required assisted ventilation for longer than 3 weeks. Four of the five infants did not receive any oral feedings. Synthetic L-amino acids were given for a mean of 33 + 5.7 days (range, 22 to 52 days). The diagnosis of cholestasis was made clinically in only one neonate. Laboratory findings in this infant included persistently elevated direct bilirubin values at 4 weeks of age which disappeared 59 days following the cessation of parenteral alimentation. SGOT, SGPT, and other liver studies were normal. Pathologic findings in the five infants included the presence of bile casts of varying size in the bile ductules and canaliculi. In addition, bile pigment was present within the liver cells. Inflammatory changes were not present and liver architecture was well oreserved. Eosinophils and lympttocytes were seen occasionally~ Biliary cholestasis may be regarded as an important complication of hyperalimentation, even if the fluids are modified and given peripherally. High direct bilirubinemia may be the only clinical manifestation. COMMENT: It was speculated that specific amino acids, such as methionine, may be directly responsible for cholestasis. The finding of particularly high levels of methionine and glycine in one of the patients was considered a significant observation. The need to inform manufacturers of hyperalimentation solutions to lower the concentration of some of the specific amino acids was emphasized.
33. The N-syndrome. A "new"multiple congenital anomaly-mental retardation syndrome Russell Hess,* Elisabeth Kaveggia,* and John M. Opitz, Madison, Wis. Two brothers from a nonconsanguineous sibship are reported who have a previously undescribed MCA-MR syndrome consisting of characteristic appearance, severe mental and growth
The Journal o f Pediatrics June 1974
retardation with visual impairment and deafness; skull, face, eye, ear, dental and skeletal anomalies; cryptorchidism and hypospadias; high fingerprint ridge count and spasticity. Each has a normal karyotype. The older of the two is now 13 years old and receiving total institutional care, but is medically stable. The younger died of lymphosarcoma at the age of 5 8/12. Autopsy study of the brain showed abnormal cerebral cortical cytoarchitecture and marked dysmorphology of the pyramidal cells. These sibs may have a "private syndrome" with a presently undetectable rearrangement in chromosome material or may represent a syndrome characterized by either autosomal recessive or X-linked inheritance. COMMENT: This paper introduces the concept of a "private" syndrome of multiple anomalies and mental retardation in two brothers. The terminology is a good one because it emphasizes that mutation is a continuing process in man, resulting in infinite possibilities of variation. Most of the variations will have negative consequences as suggested by the present cases. A good analogy would be the "private" versus "public" blood types.
34. Nitrogen (N) balance and calorie efficiency in growthfailure of prenatal onset Ingeborg Krieger and Charles F. Whitten, Detroit, Mich. The progeny of underfed mother rats, which have irreversible growth failure, may have characteristics in common with infants who are small for date at birth and remain small. Abnormalities of feed efficiency and N balance have been reported in such rats (J. Nutr. 94: 20, 1968). Comparable studies were therefore done in eight infants with dwarfing syndromes of prenatal onset (six primordial dwarfs, one Seckel's, and one Silver's syndrome). They were force fed to induce accelerated weight gain. The data are compared with those obtained in six new and 26 previously studied controls: growth failure due to malnutrition (18) or associated with congential heart disease (8). N balance was measured continuously over 14 days (average). Calorie efficiency was measured by relating residual calories to weight gain (Residual calorie = total calorie intake minus BMR, minus a fixed amount for activity). The ratio was 8.62, which is significantly higher than in controls (p< 0.01). The highest ratio was seen in Seckel's syndrome (15.5). Since these patients had a significantly lower BMR than controls (p< 0.001), inefficiency was not evident when relating the total calorie intake of 130 calorie per kilogram per day (controls: 141) to weight gain, 5.6 gm. per kilogram per day (controls: 7.7). Mean N retention was 210 rag. per kilogram per day (controls: 218). N absorption was normal (86 to 95 per cent of intake) in all but the Seckel's and Silver's syndrome (79 and 80 per cent). Gram weight gain per gram N retention was low (16.3 to 19.6) in four cases with an average weight gain of 4.0 grn. per kilogram per day; values of 28.4 to 39.0 gm. per gram N were seen during periods of higher weight gain (6.8 gm. per kilogram per day). Similar observations were made in controls during 10 periods of high and low weight gain (7.7 and 2.2 gin. per kilogram per day). The data indicate that dwarfing syndromes have a decreased calorie efficiency; N retentions can be induced readily; weight gain occurs providing enough calories are given. COMMENT: When asked if the ratio for weight gain over nitrogen (N) retention reflects efficiency, Dr. Krieger replied, no, the
Abstracts
dysplasia (BPD), in general, the need for oxygen concentration of 60 per cent or more was of shorter duration in infants who received IPPV with PEEP than in those with IPPV alone. Since prolonged duration of high inspired oxygen concentration is known to induce BPD, the authors attributed the lower incidence of BPD in the IPPV plus PEEP group to this fact.
32. Biliary cholestasis associated with peripheral administration of L-amino acids and dextrose M. Zarif,* D. Vidyasagar, P. B. Szanto,* and R. S. Pildes, Chicago, Ill, A modified form of parenteral alimentation (dextrose, 10 per cent and synthetic L-amino acids, protein 1.7 to 3.4 gin. per cent) has been used extensively in our nursery for low-birth-weight infants who required prolonged assisted ventilation or who were unable to tolerate oral feedings. Biliary cholestasis was diagnosed at autopsy in four infants who received modified alimentation and in a fifth infant who received total p~enteral alimentation (dextrose 20 per cent, L-amino acids 3.8 per cent) via a central venous catheter. All five infants weighed tess than 1,250 grams at birth (range, 943 to 1,247 grams), were appropriate for their gestational age and required assisted ventilation for longer than 3 weeks. Four of the five infants did not receive any oral feedings. Synthetic L-amino acids were given for a mean of 33 + 5.7 days (range, 22 to 52 days). The diagnosis of cholestasis was made clinically in only one neonate. Laboratory findings in this infant included persistently elevated direct bilirubin values at 4 weeks of age which disappeared 59 days following the cessation of parenteral alimentation. SGOT, SGPT, and other liver studies were normal. Pathologic findings in the five infants included the presence of bile casts of varying size in the bile ductules and canaliculi. In addition, bile pigment was present within the liver cells. Inflammatory changes were not present and liver architecture was well oreserved. Eosinophils and lympttocytes were seen occasionally~ Biliary cholestasis may be regarded as an important complication of hyperalimentation, even if the fluids are modified and given peripherally. High direct bilirubinemia may be the only clinical manifestation. COMMENT: It was speculated that specific amino acids, such as methionine, may be directly responsible for cholestasis. The finding of particularly high levels of methionine and glycine in one of the patients was considered a significant observation. The need to inform manufacturers of hyperalimentation solutions to lower the concentration of some of the specific amino acids was emphasized.
33. The N-syndrome. A "new"multiple congenital anomaly-mental retardation syndrome Russell Hess,* Elisabeth Kaveggia,* and John M. Opitz, Madison, Wis. Two brothers from a nonconsanguineous sibship are reported who have a previously undescribed MCA-MR syndrome consisting of characteristic appearance, severe mental and growth
The Journal o f Pediatrics June 1974
retardation with visual impairment and deafness; skull, face, eye, ear, dental and skeletal anomalies; cryptorchidism and hypospadias; high fingerprint ridge count and spasticity. Each has a normal karyotype. The older of the two is now 13 years old and receiving total institutional care, but is medically stable. The younger died of lymphosarcoma at the age of 5 8/12. Autopsy study of the brain showed abnormal cerebral cortical cytoarchitecture and marked dysmorphology of the pyramidal cells. These sibs may have a "private syndrome" with a presently undetectable rearrangement in chromosome material or may represent a syndrome characterized by either autosomal recessive or X-linked inheritance. COMMENT: This paper introduces the concept of a "private" syndrome of multiple anomalies and mental retardation in two brothers. The terminology is a good one because it emphasizes that mutation is a continuing process in man, resulting in infinite possibilities of variation. Most of the variations will have negative consequences as suggested by the present cases. A good analogy would be the "private" versus "public" blood types.
34. Nitrogen (N) balance and calorie efficiency in growthfailure of prenatal onset Ingeborg Krieger and Charles F. Whitten, Detroit, Mich. The progeny of underfed mother rats, which have irreversible growth failure, may have characteristics in common with infants who are small for date at birth and remain small. Abnormalities of feed efficiency and N balance have been reported in such rats (J. Nutr. 94: 20, 1968). Comparable studies were therefore done in eight infants with dwarfing syndromes of prenatal onset (six primordial dwarfs, one Seckel's, and one Silver's syndrome). They were force fed to induce accelerated weight gain. The data are compared with those obtained in six new and 26 previously studied controls: growth failure due to malnutrition (18) or associated with congential heart disease (8). N balance was measured continuously over 14 days (average). Calorie efficiency was measured by relating residual calories to weight gain (Residual calorie = total calorie intake minus BMR, minus a fixed amount for activity). The ratio was 8.62, which is significantly higher than in controls (p< 0.01). The highest ratio was seen in Seckel's syndrome (15.5). Since these patients had a significantly lower BMR than controls (p< 0.001), inefficiency was not evident when relating the total calorie intake of 130 calorie per kilogram per day (controls: 141) to weight gain, 5.6 gm. per kilogram per day (controls: 7.7). Mean N retention was 210 rag. per kilogram per day (controls: 218). N absorption was normal (86 to 95 per cent of intake) in all but the Seckel's and Silver's syndrome (79 and 80 per cent). Gram weight gain per gram N retention was low (16.3 to 19.6) in four cases with an average weight gain of 4.0 grn. per kilogram per day; values of 28.4 to 39.0 gm. per gram N were seen during periods of higher weight gain (6.8 gm. per kilogram per day). Similar observations were made in controls during 10 periods of high and low weight gain (7.7 and 2.2 gin. per kilogram per day). The data indicate that dwarfing syndromes have a decreased calorie efficiency; N retentions can be induced readily; weight gain occurs providing enough calories are given. COMMENT: When asked if the ratio for weight gain over nitrogen (N) retention reflects efficiency, Dr. Krieger replied, no, the