L E T T E R S TO T H E E D I T O R Clinical notes
"Clinical Notes" represent clinical a n d / o r laboratory experiences which can be presented in 200 to 400 words, 3 or 4 references, and, if contributory, one illustration or short table. "Clinical Notes" are subject to the same critical peer review and editing as papers published in other sections o f the JOURNAL.
Protein level in the meconium of a homozygotic and a heterozygotic infant with cystic fibrosis
T a b l e I. P r o t e i n c o n t e n t o f m e c o n i u m
Homozygote Heterozygote Control No. 1 Control No. 2
To the Editor: A raised protein level in the meconium was described by Buchanan and Rapaport I in an infant with meconium ileus. Estimation of the protein content of meconium was suggested as a possible screening procedure for cystic fibrosis by Schutt and Isles.2 Green and Shwachman ~ suggested that children with false positive results may represent heterozygotes, but this was not substantiated by Prosser and associates? In our patient, the second child of a married couple heterozygous for cystic fibrosis, the meconium protein content was higher than that of controls. He has no symptoms o f cystic fibrosis. The determination of sodium and chloride ions in the sweat excluded homozygosity; the bromide test led us to conclude the child to be a heterozygote, We examined the meconium samples by electrophoresis and densitometry, and also by polarography. The protein content in the meconium was raised two to three times in the case o f the heterozygotic infant, and 14 to 15 times in the case of a homozygotic infant, as compared with the controls (Table I). Kollberg and Hellsing ~ reported that meconium levels of albumin of greater than 20 m g / g m dried meconium were of significance in the detection of cystic fibrosis. However, the immunochemical method of Bull and associates '~identifies a level of 4 rag/gin dried meconium as significant. In our patient the protein content of the meconium, the majority of which was albumin, was two- to threefold that of the controls. This elevated protein content, however, was not characteristic of homozygosity. Our results lead us to conclude that a high protein content of meconium does not unconditionally indicate the homozygotic state for cystic fibrosis. In the case of an elevated meconium protein content or a positive screening finding, further investigations are necessary in order to establish homozygosity or heterozygosity. It would appear that heterozygosity for cystic fibrosis is not completely without abnormality. Our findings perhaps explaifl "false positive" results recorded in the literature. High-protein
(mg/gm)
dry
substance
Day of birth
Fourth day
38.12 6.46 1.48 2.92
76.40 12.67 5.06 3.50
content in the meconium may be useful in the identification of heterozygotes too.
Z. Pap]), M.D. T. Karsai, M.D. K. Gyurkovits, M.D. Human Genetics Laboratory Department of Obstetrics and Gynecology Department of Biochemistry University Medical School Debrecen, Hungary Department of Pediatrics University Medical School Szeged, Hungary REFERENCES
1.
2. 3.
4.
5. 6.
Buchanan DJ, and Rapaport S: Chemical comparison of normal meconium and meconium from a patient with meconium ileus, Pediatrics 9:304, 1952. Schutt WH, and Isles TE: Protein in meconium from meconium ileus, Arch Dis Child 43:178, 1968. Green MN, and Shwachman H: Presumptive tests for cystic fibrosis based on serum protein in meconium, Pediatrics 41:989, 1968. Prosser R, Owen H, Bull F, Parry B, Smerkinich J, Goodwin HA, and Dathan J: Screening for cystic fibrosis by examination of meconium, Arch Dis Child 49:597, 1974. Kollberg H, and Hellsing K: Screening for cystic fibrosis, Arch Dis Child 47:836, 1972. Bull FE, Gladwin DEO, and Griffiths A: Immunochemical method for detection o f albumin in human meconium, Arch Dis Child 49:602, 1974.
The Journal o f P E D I A T R I C S Vol. 88, No. 1, pp. 151-17l
15 1
"Clinical Notes" represent clinical a n d / o r laboratory experiences which can be presented in 200 to 400 words, 3 or 4 references, and, if contributory, one illustration or short table. "Clinical Notes" are subject to the same critical peer review and editing as papers published in other sections o f the JOURNAL.
Protein level in the meconium of a homozygotic and a heterozygotic infant with cystic fibrosis
T a b l e I. P r o t e i n c o n t e n t o f m e c o n i u m
Homozygote Heterozygote Control No. 1 Control No. 2
To the Editor: A raised protein level in the meconium was described by Buchanan and Rapaport I in an infant with meconium ileus. Estimation of the protein content of meconium was suggested as a possible screening procedure for cystic fibrosis by Schutt and Isles.2 Green and Shwachman ~ suggested that children with false positive results may represent heterozygotes, but this was not substantiated by Prosser and associates? In our patient, the second child of a married couple heterozygous for cystic fibrosis, the meconium protein content was higher than that of controls. He has no symptoms o f cystic fibrosis. The determination of sodium and chloride ions in the sweat excluded homozygosity; the bromide test led us to conclude the child to be a heterozygote, We examined the meconium samples by electrophoresis and densitometry, and also by polarography. The protein content in the meconium was raised two to three times in the case o f the heterozygotic infant, and 14 to 15 times in the case of a homozygotic infant, as compared with the controls (Table I). Kollberg and Hellsing ~ reported that meconium levels of albumin of greater than 20 m g / g m dried meconium were of significance in the detection of cystic fibrosis. However, the immunochemical method of Bull and associates '~identifies a level of 4 rag/gin dried meconium as significant. In our patient the protein content of the meconium, the majority of which was albumin, was two- to threefold that of the controls. This elevated protein content, however, was not characteristic of homozygosity. Our results lead us to conclude that a high protein content of meconium does not unconditionally indicate the homozygotic state for cystic fibrosis. In the case of an elevated meconium protein content or a positive screening finding, further investigations are necessary in order to establish homozygosity or heterozygosity. It would appear that heterozygosity for cystic fibrosis is not completely without abnormality. Our findings perhaps explaifl "false positive" results recorded in the literature. High-protein
(mg/gm)
dry
substance
Day of birth
Fourth day
38.12 6.46 1.48 2.92
76.40 12.67 5.06 3.50
content in the meconium may be useful in the identification of heterozygotes too.
Z. Pap]), M.D. T. Karsai, M.D. K. Gyurkovits, M.D. Human Genetics Laboratory Department of Obstetrics and Gynecology Department of Biochemistry University Medical School Debrecen, Hungary Department of Pediatrics University Medical School Szeged, Hungary REFERENCES
1.
2. 3.
4.
5. 6.
Buchanan DJ, and Rapaport S: Chemical comparison of normal meconium and meconium from a patient with meconium ileus, Pediatrics 9:304, 1952. Schutt WH, and Isles TE: Protein in meconium from meconium ileus, Arch Dis Child 43:178, 1968. Green MN, and Shwachman H: Presumptive tests for cystic fibrosis based on serum protein in meconium, Pediatrics 41:989, 1968. Prosser R, Owen H, Bull F, Parry B, Smerkinich J, Goodwin HA, and Dathan J: Screening for cystic fibrosis by examination of meconium, Arch Dis Child 49:597, 1974. Kollberg H, and Hellsing K: Screening for cystic fibrosis, Arch Dis Child 47:836, 1972. Bull FE, Gladwin DEO, and Griffiths A: Immunochemical method for detection o f albumin in human meconium, Arch Dis Child 49:602, 1974.
The Journal o f P E D I A T R I C S Vol. 88, No. 1, pp. 151-17l
15 1
