803
frequency of the above-mentioned alleles in the general and in our control sample of 71 healthy children only 2 had partly reduced ASA activity.3 On the other hand, this frequency of 21 % is similar to the 26% found in 140 .3 children with neurological disturbances These results support the hypothesis of a non-chance association between a reduced ASA activity and psychiatric disorders.3,4 Partly of the
population, is only 7%/
ASA deficient individuals could be more liable to these disturbances in the presence of concomitant factors, as suggested for other metabolic diseases with autosomal recessive inheritance.S It seems important to extend this analysis to children with mild mental retardation of unknown aetiology, to establish the association between mental retardation and mutant genotypes at the ASA locus. Neurological Clinic, Univeristy of Bologna, 40123 Bologna, Italy, and Neurology Service, Policlinico S.
Orsola-Malpighi,
Bologna
SIMONETTA SANGIORGI MIRELLA MOCHI SERGIO CAMMARATA GIULIA BENASSI MARIA GUARINO ROBERTO D’ALESSANDRO
1. Benassi G, Guarino M, Cammarata S, et al. An epidemiological study on severe mental retardation among school children in Bologna, Italy Develop Med Child Neurol
1990, 32: 895-901. 2. Hohenschutz C, Eich P, Friedl W, Waheed A, Conzelmann E, Propping P. Pseudodeficiency of arylsulfatase A: a common genetic polymorphism with possible disease implications. Hum Genet 1989; 82: 45-48. 3. Sangiorgi S, Ferlini A, Zanetti A, Mochi M Reduced activity of arylsulfatase A and predisposition for neurological disorders: analysis of 140 pediatric patients. Am J Med Genet (in press). 4. Shah SN, Johnson RC, Stone RK, Mahon-Haft H. Prevalence of partial cerebroside sulfate sulfatase (arylsulfatase A) defect in adult psychiatric patients. Biol Psychiatry 1985; 20: 50-57. 5 Vogel F. Clinical consequences of heterozygosity for autosomal recessive diseases. Clin Genet 1984; 25: 381-415.
Cross-reactivity between antibodies to thyroid microsomal antigens and myeloperoxidase SIR,- Thyroid peroxidase (TPO) accounts for almost all of the antigenic determinants recognised by microsomal antibodies in autoimmune thyroiditis. Antibodies to myeloperoxidase, an enzyme found in neutrophils, have been reported in several vasculitic diseases and are helpful in diagnosis and patient follow-up. Since there is over 40% structural homology between TPO and myeloperoxidase (MPO),2 there may be cross-reactivity between antibodies directed against these enzymes in patients with vasculitis. Commercially available kits for measurement of thyroid microsomal and thyroglobin antibodies by agglutination (Fujirebio, Ames), and enzyme immunoassays for MPO and antineutrophil cytoplasmic antibody (ANCA) (BioCarb) were used. In addition, an
indirect immunofluorescence
test on
alcohol-fixed human
neutrophils was able to identify antibodies to neutrophil cytoplasmic components. We studied two groups of patients. Group 1 included 69 patients with vasculitic diseases, 29 MPOantibody positive and 40 MPO-antibody negative. Group 2 had 99 patients whose sera were sent for routine thyroid antibody testing; 64 were thyroid-microsomal-antibody positive (titre 1600) and 35 were thyroid-microsomal-antibody negative. ENZYME IMMUNOASSAY RESULTS IN VASCULITIS AND THYROID PATIENTS
’p=0 0001
16 of 99 group 2 sera contained antibodies to myeloperoxidase. None of these patients showed typical cytoplasmic or perinuclear ANCA staining, or had clinical evidence of vasculitis. The distribution of thyroid-microsomal (TM) antibodies in these group 2 patients was significantly different from that observed among MPO-antibody positive patients with vasculitis (p = 0,0001, table). No evidence for cross-reactivity between MPO and TPO antibodies, as measured by a new commercial radioimmunoassay, has been found (unpublished data). An explanation for this apparent inconsistency may be that thyroid-microsomal antibodies are highly heterogeneous.4 Antibodies against native TPO correspond to those that react in the standard microsomal agglutination test used in normal clinical practice.5 Sera that contain antibodies to thyroid microsomes do not react with native myeloperoxidase but most do react with denatured/reduced enzyme,s which might explain some of our results. However, sera with antibodies to MPO would then be expected to react in the thyroid antibody test, but this was not found. Our data suggest that in vasculitis antibodies to MPO are directed against epitopes that are not shared with TPO, while in thyroid diseases a proportion of sera, especially if thyroid-microsomal-antibody positive, contain antibodies against epitopes common to both TPO and MPO. Since some thyroid-microsomal-antibody negative sera also gave positive reactions in the MPO-antibody assay, there may be a third antigen that cross-reacts with both TPO and MPO. It remains to be shown whether these patterns define particular patient subsets. Division of Clinical Immunology, Department of Clinical Microbiology, University Hospital of Tampere, SF 33520 Tampere, Finland
ANNA-MAIJA HAAPALA
Institute of Biomedical Sciences, University of Tampere
HEIKKI HYÖTY
Department of Medicine, University Hospital of Tampere
ESA SOPPI
JUKKA MUSTONEN AMOS PASTERNACK
1. Mariotti S, Anelli S, Ruf J, et al. Comparison of serum thyroid microsomal and thyroid peroxidase autoantibodies m thyroid diseases. J Clin Endocrinol Metab 1987; 65: 987-93. 2. Kimura S, Ikeda-Saito M. Human myeloperoxidase and thyroid peroxidase, two enzymes with separate and distinct physiological functions are evolutionary related members of the same gene family. Proteins 1988; 3: 113-20. 3. Soppi E, Haapala AM, Laine S, Salmi J. Performance of two agglutination techniques in the detection of thyroid antibodies and assessment of their clinical significance. Scand J Clin Lab Invest 1990; 50: 885-90. 4. Banga JP, Tomlinson RWS, Doble N, Odell E, McGregor AM. Thyroid microsomal/thyroid peroxidase autoantibodies show discrete patterns of crossreactivity to myeloperoxidase, lactoperoxidase and horseradish peroxidase. Immunology 1989; 67: 197-203. 5. Hamada N, Jaeduck N, Portmann L, Ito K, De Groot LJ. Antibodies against denatured and reduced thyroid microsomal antigen in autoimmune thyroid disease. J Clin Endocrinol Metab 1987; 64: 230-38
Low frequency of monosomy 20 mosaicism in a liveborn infant with minor dysmorphic features SIR,-Non-X chromosome
monosomy is
rare
and has been
reliably only for chromosome 21 in a full-term pregnancy.l Monosomy 20 is a cytogenetic finding that has not been reported to our knowledge, although there have been a few cases of partial monosomy 20 associated with other chromosomal duplication and deletion syndromes.2 We present the clinical and cytogenetic findings of a livebom female infant with minor dysmorphic features who had monosomy 20 in a low percentage of described
cells. Our patient was born at 28 weeks’ gestation. Both parents had been studied cytogenetically because of a history of recurrent miscarriage (gravida 6, para 1); there was no family history of birth defects or mental retardation. The pregnancy was complicated by gestational diabetes. Birthweight was 1335 g; birth length was 38 cm, and head circumference was 26 cm. The body had excessive fine light hair. There was a notch in both ear lobes and the ears were mildly rotated posteriorly. There was a depressed nasal bridge, mild micrognathia, and redundancy of skin at the back of the neck. Genitalia were those of a normal female. Ultrasound of the head
frequency of the above-mentioned alleles in the general and in our control sample of 71 healthy children only 2 had partly reduced ASA activity.3 On the other hand, this frequency of 21 % is similar to the 26% found in 140 .3 children with neurological disturbances These results support the hypothesis of a non-chance association between a reduced ASA activity and psychiatric disorders.3,4 Partly of the
population, is only 7%/
ASA deficient individuals could be more liable to these disturbances in the presence of concomitant factors, as suggested for other metabolic diseases with autosomal recessive inheritance.S It seems important to extend this analysis to children with mild mental retardation of unknown aetiology, to establish the association between mental retardation and mutant genotypes at the ASA locus. Neurological Clinic, Univeristy of Bologna, 40123 Bologna, Italy, and Neurology Service, Policlinico S.
Orsola-Malpighi,
Bologna
SIMONETTA SANGIORGI MIRELLA MOCHI SERGIO CAMMARATA GIULIA BENASSI MARIA GUARINO ROBERTO D’ALESSANDRO
1. Benassi G, Guarino M, Cammarata S, et al. An epidemiological study on severe mental retardation among school children in Bologna, Italy Develop Med Child Neurol
1990, 32: 895-901. 2. Hohenschutz C, Eich P, Friedl W, Waheed A, Conzelmann E, Propping P. Pseudodeficiency of arylsulfatase A: a common genetic polymorphism with possible disease implications. Hum Genet 1989; 82: 45-48. 3. Sangiorgi S, Ferlini A, Zanetti A, Mochi M Reduced activity of arylsulfatase A and predisposition for neurological disorders: analysis of 140 pediatric patients. Am J Med Genet (in press). 4. Shah SN, Johnson RC, Stone RK, Mahon-Haft H. Prevalence of partial cerebroside sulfate sulfatase (arylsulfatase A) defect in adult psychiatric patients. Biol Psychiatry 1985; 20: 50-57. 5 Vogel F. Clinical consequences of heterozygosity for autosomal recessive diseases. Clin Genet 1984; 25: 381-415.
Cross-reactivity between antibodies to thyroid microsomal antigens and myeloperoxidase SIR,- Thyroid peroxidase (TPO) accounts for almost all of the antigenic determinants recognised by microsomal antibodies in autoimmune thyroiditis. Antibodies to myeloperoxidase, an enzyme found in neutrophils, have been reported in several vasculitic diseases and are helpful in diagnosis and patient follow-up. Since there is over 40% structural homology between TPO and myeloperoxidase (MPO),2 there may be cross-reactivity between antibodies directed against these enzymes in patients with vasculitis. Commercially available kits for measurement of thyroid microsomal and thyroglobin antibodies by agglutination (Fujirebio, Ames), and enzyme immunoassays for MPO and antineutrophil cytoplasmic antibody (ANCA) (BioCarb) were used. In addition, an
indirect immunofluorescence
test on
alcohol-fixed human
neutrophils was able to identify antibodies to neutrophil cytoplasmic components. We studied two groups of patients. Group 1 included 69 patients with vasculitic diseases, 29 MPOantibody positive and 40 MPO-antibody negative. Group 2 had 99 patients whose sera were sent for routine thyroid antibody testing; 64 were thyroid-microsomal-antibody positive (titre 1600) and 35 were thyroid-microsomal-antibody negative. ENZYME IMMUNOASSAY RESULTS IN VASCULITIS AND THYROID PATIENTS
’p=0 0001
16 of 99 group 2 sera contained antibodies to myeloperoxidase. None of these patients showed typical cytoplasmic or perinuclear ANCA staining, or had clinical evidence of vasculitis. The distribution of thyroid-microsomal (TM) antibodies in these group 2 patients was significantly different from that observed among MPO-antibody positive patients with vasculitis (p = 0,0001, table). No evidence for cross-reactivity between MPO and TPO antibodies, as measured by a new commercial radioimmunoassay, has been found (unpublished data). An explanation for this apparent inconsistency may be that thyroid-microsomal antibodies are highly heterogeneous.4 Antibodies against native TPO correspond to those that react in the standard microsomal agglutination test used in normal clinical practice.5 Sera that contain antibodies to thyroid microsomes do not react with native myeloperoxidase but most do react with denatured/reduced enzyme,s which might explain some of our results. However, sera with antibodies to MPO would then be expected to react in the thyroid antibody test, but this was not found. Our data suggest that in vasculitis antibodies to MPO are directed against epitopes that are not shared with TPO, while in thyroid diseases a proportion of sera, especially if thyroid-microsomal-antibody positive, contain antibodies against epitopes common to both TPO and MPO. Since some thyroid-microsomal-antibody negative sera also gave positive reactions in the MPO-antibody assay, there may be a third antigen that cross-reacts with both TPO and MPO. It remains to be shown whether these patterns define particular patient subsets. Division of Clinical Immunology, Department of Clinical Microbiology, University Hospital of Tampere, SF 33520 Tampere, Finland
ANNA-MAIJA HAAPALA
Institute of Biomedical Sciences, University of Tampere
HEIKKI HYÖTY
Department of Medicine, University Hospital of Tampere
ESA SOPPI
JUKKA MUSTONEN AMOS PASTERNACK
1. Mariotti S, Anelli S, Ruf J, et al. Comparison of serum thyroid microsomal and thyroid peroxidase autoantibodies m thyroid diseases. J Clin Endocrinol Metab 1987; 65: 987-93. 2. Kimura S, Ikeda-Saito M. Human myeloperoxidase and thyroid peroxidase, two enzymes with separate and distinct physiological functions are evolutionary related members of the same gene family. Proteins 1988; 3: 113-20. 3. Soppi E, Haapala AM, Laine S, Salmi J. Performance of two agglutination techniques in the detection of thyroid antibodies and assessment of their clinical significance. Scand J Clin Lab Invest 1990; 50: 885-90. 4. Banga JP, Tomlinson RWS, Doble N, Odell E, McGregor AM. Thyroid microsomal/thyroid peroxidase autoantibodies show discrete patterns of crossreactivity to myeloperoxidase, lactoperoxidase and horseradish peroxidase. Immunology 1989; 67: 197-203. 5. Hamada N, Jaeduck N, Portmann L, Ito K, De Groot LJ. Antibodies against denatured and reduced thyroid microsomal antigen in autoimmune thyroid disease. J Clin Endocrinol Metab 1987; 64: 230-38
Low frequency of monosomy 20 mosaicism in a liveborn infant with minor dysmorphic features SIR,-Non-X chromosome
monosomy is
rare
and has been
reliably only for chromosome 21 in a full-term pregnancy.l Monosomy 20 is a cytogenetic finding that has not been reported to our knowledge, although there have been a few cases of partial monosomy 20 associated with other chromosomal duplication and deletion syndromes.2 We present the clinical and cytogenetic findings of a livebom female infant with minor dysmorphic features who had monosomy 20 in a low percentage of described
cells. Our patient was born at 28 weeks’ gestation. Both parents had been studied cytogenetically because of a history of recurrent miscarriage (gravida 6, para 1); there was no family history of birth defects or mental retardation. The pregnancy was complicated by gestational diabetes. Birthweight was 1335 g; birth length was 38 cm, and head circumference was 26 cm. The body had excessive fine light hair. There was a notch in both ear lobes and the ears were mildly rotated posteriorly. There was a depressed nasal bridge, mild micrognathia, and redundancy of skin at the back of the neck. Genitalia were those of a normal female. Ultrasound of the head
