Volume 87 Number 5
Letters to the Editor
2. Hansen OE, and Lund MA: Akut cerebellar ataksi ved infektios mononukleose, Nord Med 77:153, 1967. 3. Gilbert JW, and Culebras A: Cerebellitis in infectious mononucleosis, JAMA 220"727, 1972. 4. Bennett DR, and Peters HA: Acute cerebellar syndrome secondary to infectious mononucleosis in a fifty-two year old man, Ann Intern Med 55:147, i961. 5. Hoyne RM: Involvement of the central nervous system in infectious mononucleosis, Arch Neurol Psychiat 63:606, 19501 6. Schoenberger HB: Cerebellar ataxia associated with infectious mononucleosis, J Am Coll Health Assoc 14:213, 1966.
833
demonstrate any impairment in the i.lnmunologic functions of neutrophils or lymphocytes from our patient. The observation that these patients have recurrent and severe infections remains, but the basis for their altered resistance to infection is still unanswered. Thomas A. Fleisher, M.D. J. Nevin Isenberg, M.D., Ph.D. Harvey L. Sharp, M.D. Gastroenterology Section Department o f Pediatrics University of Minnesota Minneapolis, Minn~ 55455 REFERENCES
Leukocyte function in aspartylglucosaminuria To the Editor: We have recently described a 5-year-old girl with aspartylglucosaminuria (AGU), a metabolic defect in glycoprotein catabolism resulting from a deficiency of the lysosomal enzyme, aspartylglucosamine amido hydrolase. 1 Clinically, patients with this disorder have been, noted to have recurrent respiratory infections and a variety of other purulent lesions. ~ A theory forwarded to explain this altered resistance to infection proposes that the abnormality in lysosomal enzyme content leads to a secondary disturbance in the leukocyte functions related to the immunologic defense mechanism. 2 We have shown that the ultrastructural morphology of the lysosomes of neutrophils and lymphocytes in this disease is altered with respect to size and matrix content) In order to critically examine this hypothesis, an evaluation of neutrophil and lymphocyte function wa s performed on ce!ls prepared from our patient. LABORATORY
STUDIES
The leukocyte counts and differentials were within normal limits on all testings. In v!yo leukocyte migrations as measured by the skin window technique was interpreted as normal (Dr. Arthur Page). In vitro neutrophil chemotaxis, and phagocytosis and killing of Staphlococcus aureus 502A and Escherichia coli K12 were normal (Dr. Paul Quie's laboratory). In addition, the serum ops0nic activity to the above bacteria was normal. Lymphocyte function was studied in vivo with skin tests which yielded weak responses to SKSD and Candida. In vitro lymphocyte evaluation revealed normal numbers of "B" lymphocytes and "T" lymphocytes. Functional lymphocyte evaluation included normal serum immunoglobulin levels (IgG, IgM, IgA, IgE), normal hemagglutination titers, normal antibody response tO diphtheria and tetanus toxoid, and normal mitogenic stimulation (PHA and Con A). Thus, despite the morphologic abnormalities noted in the lysosomes of lcukocytes in AGU, we have been unable to
1. Isenberg JN and Sharp HL: Aspartylglucosaminuria: psychomotor retardation masquerading as a mucopolysaccharidosis, J PEDXATR86:713, 1975. 2. Autio S: Aspartylglucosaminuria-analysis of thirty-four patients, J Ment Defic Res, Monograph Series I, 1972. 3. Isenberg JN, and Sharp HL: Aspartylglucosam~nuria: Biochemical and ultrastructural characteristics unique to this visceral storage disease, Human Pathol (in press).
Hypolycorrhachia in young infants with viral meningitis To the Editor: From June through August, 1973, 36 children with aseptic meningitis were hospitalized at the Children's Hospital of Philadelphia. An attempt at virus isolation was made with specimens from 24 patients. Positive viral isolates were recovered from 14 patients, 8 of which were coxsackievirus B-2. Virus was isolated from the cerebrospinal fluid ( C S F ) i n three instances, and from the pharynx, throat, and rectum in eleven instances. Alihough acute and convalescent serum were not available from all of the patients studied, paired serum specimens of 12 patients from Philadelphia with aseptic meningitis were submitted to the Pennsylvania State Laboratory: six showed four-fold antibody titer rises to Coxsackie virus B - 2 or high-titer neutralizing antibodies in both specimens. Furthermore, Coxsackie virus B-2 was the strain responsible for most of the cases of aseptic meningitis from the Philadelphia area reporte d to the State Laboratory during the summer of 19731 A striking feature of the outbreak was the age distribution of the patients. Half of the infants affected were less than 2 months old, and more than three-fourths of those affected were less than 2 1/2 years old. Another impressive feature was the degree of hypoglycorrhachia. In one-third of the patients studied, the CSF glucose concentration was less than 50% of a simultaneously obtained blood glucose, and in more than three-fourths of the patients, the
834
Letters to the Editor
CSF glucose concentration was less than 67% of a simultaneously obtained blood glucose determination. The lowest value recorded was a CSF glucose of 18 mg/dl with a simultaneous blood sugar of 81 mg/dl in a 7-week-old infant. Although there have been reports of low CSF sugar concentrations in viral infections of the central nervous system, particularly with mumps,! lymphocytic choriomening!tis,~herpes, and eastern equine encephalitis, ~ the degree of hypoglycorrhachia noted in the patients in this epidemic has not bee n previously recorded in cases of enteroviral aseptic meningitis. Ellis D. Avner, M.D. Children's Hospital of Philadelphia 34 Civic Center Blvd. Philadelphia, Pa. 19104 Jay Satz, Ph.D., Pennsylvania State Laboratories 2100 W. Girard.Ave. Philadelphia, Pa. 19130 Stanley A. Plotkin, M.D. Children's Hospital o f Philadelphia 34 Civic Center Blvd. Philqdelphia, Pa. 19104
REFERENCES
1. Wilfert CM: Mumps meningoencephalitis with low cerebrospinal fluid glucose, prolonged pleocytosis, and elevation of protein, N Engl J Med; 280:855, 1969. 2. Adair CV, Gauld RL, Smadel JE, et al: Aseptic meningitis, a disease of dNerse etiology, Ann Intern Med 39:675, 1953. 3. Winter WD Jr: Eastern equine encephalomyelitis in Massachusetts in 1955: Report of two cases in infants; N Engl J Med 255:262, 1956.
Transient thrombocytopenia in 18-trisomy To the Editor: More than 100 anomalies have been described in the 18trisomy syndrome, or Edwards syndrome. Thrombocytopenia occurs rarely, sometimes in combination with malformation of the radius? In one reported case, absent radii, platelet count of 60,000/mm 3, and decreased megakaryocytes in postmortem examination of bone marrow were notedY Another patient with radial aplasia, platelet count of 16,000/mm,~ and absent megakaFrom the New York Hospital-Cornell Medical Center, Department of Pediatrics, Division of Pediatric Hematology-Oncology. Supported in part by the Children's Blood Foundation, The Health Research Council of New York City, and The National Foundation-March o f Dimes Grant No. 365.
The Journal of Pediatrics November 1975
40,000/mm ~, negative platelet antibody test on patient and mother, and postmortem examination of bone marrow in which most megakaryocytes possessed small nuclei and strongly granulated or vacuolated cytoplasm." A patient is reported here with 18-trisomy in whom multiple anomalies, but not absent radii, and transient thrombocytopenia were noted. CASE REPORT
Patient B/G M. was the 1,800 gm product of a term uncomplicated pregnancy of a 24-year-old grava 1, para 0 Caucasian mother with no abortions and no living children. The mother was reportedly normal, but no platelet counts were obtained. The infant's Apgar score was 4 and 9 at 1 and 5 minutes, respectively; resuscitation was required. Multiple abnormalities suggestive of 18-trisomy were noted at birth, including a weak cry, small face, prominent occiput, asymmetric palpebral fissures, low-set ears, microphthalmus, short sternum, shallow respirations, systolic murmur, single umbilical artery, prominent clitoris, broad hands, flexion deformities of both index fingers, abnormal abduction of hips, left rockerbottom foot, incomplete Moro reflex, a n d petechiae. Cytogenetic study on peripheral blood was Confirmatory of Edwards syndrome, with 47, XX + 18. Roentgenologic studies revealed 11 ribs, borderline cardiomegaly, questionable malrotation of gut, normal skull and mandibles, and normal radii, Bone marrow aspiration from the right anterior tibia at 14 days of age revealed normal cellularity, erythroid hyperplasia, and absent megakaryocytes; bone marrow biopsy from the right posterior iliac crest was interpreted as slightly hypocellular with some megakaryocytes seen; the megakaryocytes were relatively smooth and agranular in appearance. The initial platelet count was 35,000/mma; white blood count 8,500/mm ~ (corrected), with 28 lymphocytes, 6 monocytes, 3 eosinophils, 45 polymorphonuclear leukocytes, 18 bands, hemoglobin concentration of 15.4 gm/dl, hematocrit value of 45%, reticulocyte count 9.8%, and 54 nucleated red blood cells/100 white blood cells. Repeat platelet counts Were 29,000/into 3 at day one, 90,000 at day 9, and 318,000 at 3 weeks of age. Serologic studies for toxoplasmosis, rubella, cytomegalovirus, and herpes were negative. Platelet antibody studies bY the serotonin release method were negative. Coagulation studies at one day of age were: prothrombin time 15.7 seconds (control 12.9), partial thromboplastin time 61.8 seconds (control 41.7), and Factor V 14%. These values were considered compatible with liver dysfunction and not indicative of disseminated intravascular coagulation. The patient's course was complicated by mild respiratory distress, by mouth bleeding induced by an oral catheter, and by seizures. The child was lost to follow-up. DISCUSSION This case illustrates that the thrombocytopenia described with 18-trisomy, a rare finding, may be transient. Patients with this syndrome may not survive long enough to follow the improvement in p!atelet count with time. Thrombocytopenia is not mentioned in the rare older survivor with 18-trisomy syndrome) but patients are too few to draw any conclusions. In patients with congenital thrombocytopenia not due to 18-trisomy, the platelet count increased with time in the survivors, though rarely did it
Letters to the Editor
2. Hansen OE, and Lund MA: Akut cerebellar ataksi ved infektios mononukleose, Nord Med 77:153, 1967. 3. Gilbert JW, and Culebras A: Cerebellitis in infectious mononucleosis, JAMA 220"727, 1972. 4. Bennett DR, and Peters HA: Acute cerebellar syndrome secondary to infectious mononucleosis in a fifty-two year old man, Ann Intern Med 55:147, i961. 5. Hoyne RM: Involvement of the central nervous system in infectious mononucleosis, Arch Neurol Psychiat 63:606, 19501 6. Schoenberger HB: Cerebellar ataxia associated with infectious mononucleosis, J Am Coll Health Assoc 14:213, 1966.
833
demonstrate any impairment in the i.lnmunologic functions of neutrophils or lymphocytes from our patient. The observation that these patients have recurrent and severe infections remains, but the basis for their altered resistance to infection is still unanswered. Thomas A. Fleisher, M.D. J. Nevin Isenberg, M.D., Ph.D. Harvey L. Sharp, M.D. Gastroenterology Section Department o f Pediatrics University of Minnesota Minneapolis, Minn~ 55455 REFERENCES
Leukocyte function in aspartylglucosaminuria To the Editor: We have recently described a 5-year-old girl with aspartylglucosaminuria (AGU), a metabolic defect in glycoprotein catabolism resulting from a deficiency of the lysosomal enzyme, aspartylglucosamine amido hydrolase. 1 Clinically, patients with this disorder have been, noted to have recurrent respiratory infections and a variety of other purulent lesions. ~ A theory forwarded to explain this altered resistance to infection proposes that the abnormality in lysosomal enzyme content leads to a secondary disturbance in the leukocyte functions related to the immunologic defense mechanism. 2 We have shown that the ultrastructural morphology of the lysosomes of neutrophils and lymphocytes in this disease is altered with respect to size and matrix content) In order to critically examine this hypothesis, an evaluation of neutrophil and lymphocyte function wa s performed on ce!ls prepared from our patient. LABORATORY
STUDIES
The leukocyte counts and differentials were within normal limits on all testings. In v!yo leukocyte migrations as measured by the skin window technique was interpreted as normal (Dr. Arthur Page). In vitro neutrophil chemotaxis, and phagocytosis and killing of Staphlococcus aureus 502A and Escherichia coli K12 were normal (Dr. Paul Quie's laboratory). In addition, the serum ops0nic activity to the above bacteria was normal. Lymphocyte function was studied in vivo with skin tests which yielded weak responses to SKSD and Candida. In vitro lymphocyte evaluation revealed normal numbers of "B" lymphocytes and "T" lymphocytes. Functional lymphocyte evaluation included normal serum immunoglobulin levels (IgG, IgM, IgA, IgE), normal hemagglutination titers, normal antibody response tO diphtheria and tetanus toxoid, and normal mitogenic stimulation (PHA and Con A). Thus, despite the morphologic abnormalities noted in the lysosomes of lcukocytes in AGU, we have been unable to
1. Isenberg JN and Sharp HL: Aspartylglucosaminuria: psychomotor retardation masquerading as a mucopolysaccharidosis, J PEDXATR86:713, 1975. 2. Autio S: Aspartylglucosaminuria-analysis of thirty-four patients, J Ment Defic Res, Monograph Series I, 1972. 3. Isenberg JN, and Sharp HL: Aspartylglucosam~nuria: Biochemical and ultrastructural characteristics unique to this visceral storage disease, Human Pathol (in press).
Hypolycorrhachia in young infants with viral meningitis To the Editor: From June through August, 1973, 36 children with aseptic meningitis were hospitalized at the Children's Hospital of Philadelphia. An attempt at virus isolation was made with specimens from 24 patients. Positive viral isolates were recovered from 14 patients, 8 of which were coxsackievirus B-2. Virus was isolated from the cerebrospinal fluid ( C S F ) i n three instances, and from the pharynx, throat, and rectum in eleven instances. Alihough acute and convalescent serum were not available from all of the patients studied, paired serum specimens of 12 patients from Philadelphia with aseptic meningitis were submitted to the Pennsylvania State Laboratory: six showed four-fold antibody titer rises to Coxsackie virus B - 2 or high-titer neutralizing antibodies in both specimens. Furthermore, Coxsackie virus B-2 was the strain responsible for most of the cases of aseptic meningitis from the Philadelphia area reporte d to the State Laboratory during the summer of 19731 A striking feature of the outbreak was the age distribution of the patients. Half of the infants affected were less than 2 months old, and more than three-fourths of those affected were less than 2 1/2 years old. Another impressive feature was the degree of hypoglycorrhachia. In one-third of the patients studied, the CSF glucose concentration was less than 50% of a simultaneously obtained blood glucose, and in more than three-fourths of the patients, the
834
Letters to the Editor
CSF glucose concentration was less than 67% of a simultaneously obtained blood glucose determination. The lowest value recorded was a CSF glucose of 18 mg/dl with a simultaneous blood sugar of 81 mg/dl in a 7-week-old infant. Although there have been reports of low CSF sugar concentrations in viral infections of the central nervous system, particularly with mumps,! lymphocytic choriomening!tis,~herpes, and eastern equine encephalitis, ~ the degree of hypoglycorrhachia noted in the patients in this epidemic has not bee n previously recorded in cases of enteroviral aseptic meningitis. Ellis D. Avner, M.D. Children's Hospital of Philadelphia 34 Civic Center Blvd. Philadelphia, Pa. 19104 Jay Satz, Ph.D., Pennsylvania State Laboratories 2100 W. Girard.Ave. Philadelphia, Pa. 19130 Stanley A. Plotkin, M.D. Children's Hospital o f Philadelphia 34 Civic Center Blvd. Philqdelphia, Pa. 19104
REFERENCES
1. Wilfert CM: Mumps meningoencephalitis with low cerebrospinal fluid glucose, prolonged pleocytosis, and elevation of protein, N Engl J Med; 280:855, 1969. 2. Adair CV, Gauld RL, Smadel JE, et al: Aseptic meningitis, a disease of dNerse etiology, Ann Intern Med 39:675, 1953. 3. Winter WD Jr: Eastern equine encephalomyelitis in Massachusetts in 1955: Report of two cases in infants; N Engl J Med 255:262, 1956.
Transient thrombocytopenia in 18-trisomy To the Editor: More than 100 anomalies have been described in the 18trisomy syndrome, or Edwards syndrome. Thrombocytopenia occurs rarely, sometimes in combination with malformation of the radius? In one reported case, absent radii, platelet count of 60,000/mm 3, and decreased megakaryocytes in postmortem examination of bone marrow were notedY Another patient with radial aplasia, platelet count of 16,000/mm,~ and absent megakaFrom the New York Hospital-Cornell Medical Center, Department of Pediatrics, Division of Pediatric Hematology-Oncology. Supported in part by the Children's Blood Foundation, The Health Research Council of New York City, and The National Foundation-March o f Dimes Grant No. 365.
The Journal of Pediatrics November 1975
40,000/mm ~, negative platelet antibody test on patient and mother, and postmortem examination of bone marrow in which most megakaryocytes possessed small nuclei and strongly granulated or vacuolated cytoplasm." A patient is reported here with 18-trisomy in whom multiple anomalies, but not absent radii, and transient thrombocytopenia were noted. CASE REPORT
Patient B/G M. was the 1,800 gm product of a term uncomplicated pregnancy of a 24-year-old grava 1, para 0 Caucasian mother with no abortions and no living children. The mother was reportedly normal, but no platelet counts were obtained. The infant's Apgar score was 4 and 9 at 1 and 5 minutes, respectively; resuscitation was required. Multiple abnormalities suggestive of 18-trisomy were noted at birth, including a weak cry, small face, prominent occiput, asymmetric palpebral fissures, low-set ears, microphthalmus, short sternum, shallow respirations, systolic murmur, single umbilical artery, prominent clitoris, broad hands, flexion deformities of both index fingers, abnormal abduction of hips, left rockerbottom foot, incomplete Moro reflex, a n d petechiae. Cytogenetic study on peripheral blood was Confirmatory of Edwards syndrome, with 47, XX + 18. Roentgenologic studies revealed 11 ribs, borderline cardiomegaly, questionable malrotation of gut, normal skull and mandibles, and normal radii, Bone marrow aspiration from the right anterior tibia at 14 days of age revealed normal cellularity, erythroid hyperplasia, and absent megakaryocytes; bone marrow biopsy from the right posterior iliac crest was interpreted as slightly hypocellular with some megakaryocytes seen; the megakaryocytes were relatively smooth and agranular in appearance. The initial platelet count was 35,000/mma; white blood count 8,500/mm ~ (corrected), with 28 lymphocytes, 6 monocytes, 3 eosinophils, 45 polymorphonuclear leukocytes, 18 bands, hemoglobin concentration of 15.4 gm/dl, hematocrit value of 45%, reticulocyte count 9.8%, and 54 nucleated red blood cells/100 white blood cells. Repeat platelet counts Were 29,000/into 3 at day one, 90,000 at day 9, and 318,000 at 3 weeks of age. Serologic studies for toxoplasmosis, rubella, cytomegalovirus, and herpes were negative. Platelet antibody studies bY the serotonin release method were negative. Coagulation studies at one day of age were: prothrombin time 15.7 seconds (control 12.9), partial thromboplastin time 61.8 seconds (control 41.7), and Factor V 14%. These values were considered compatible with liver dysfunction and not indicative of disseminated intravascular coagulation. The patient's course was complicated by mild respiratory distress, by mouth bleeding induced by an oral catheter, and by seizures. The child was lost to follow-up. DISCUSSION This case illustrates that the thrombocytopenia described with 18-trisomy, a rare finding, may be transient. Patients with this syndrome may not survive long enough to follow the improvement in p!atelet count with time. Thrombocytopenia is not mentioned in the rare older survivor with 18-trisomy syndrome) but patients are too few to draw any conclusions. In patients with congenital thrombocytopenia not due to 18-trisomy, the platelet count increased with time in the survivors, though rarely did it
