Volume 91 Number 5
Brief clinical and laboratory observations
study by_electron microscopy, 8 fluorescent antibody techniques, ~ light microscopic examination for characteristic Cowdry type A intranuclear inclusions, and direct viral isolation procedures. Experimental trials with antiviral agents in h u m a n beings have yielded variable results; however, preliminary studies with adenosine arabinoside in the treatment of HSV infection are encouraging. 1~This c o m p o u n d may be efficacious in the treatment of HSV infection provided the drug is administered early in the course of disease. 11 Despite the prompt initiation of adenosine arabinoside therapy, the patient presented developed fulminant hepatitis and DIC. HSV type 1 was isolated from his liver and adrenal glands at death after four days of therapy. The authors express their appreciation to Dr. Steve Greenberg for typing the HSV and to Ms. L. Hartsell and K. Boyle for assistance in preparation of the manuscript.
REFERENCES 1. Nahmias A J, and Roizman G: Infection with herpessimplex viruses 1 and 2, N Engl J Med 289:667, 719, 781, 1973. 2. Nahmias A J, Alford CA, and Korones SB: Infection of the newborn with herpes virus hominis, Adv Pediatr 17:185, 1970.
Renal anomalies in the fetal alcohol syndrome Martin M. DeBeukelaer, M.D.,* Carrie L. Randall, Ph.D., Charleston, S. C., and Donna R. Stroud, M.D., Greenville, S. C.
THE PURPOSE of this report is to focus attention on the renal manifestations of the fetal alcohol syndrome, by describing renal insufficiency and anomalies of the urinary tract in a patient born to an alcoholic mother.
CASE REPORT The patient was born after a 32-week gestation and uncomplicated delivery. The 31-year-old mother, a known chronic alcoFrom the Departments of Pediatrics and Psychiatry, Medical University of South Carolina, and Greenville General Hospital. *Reprint address: Department of Pediatrics, Medical University of South Carolina, 80 Barre St., Charleston, S. C. 29401.
759
3. Kipps A, Becker W, Wainwright J, et al: Fatal disseminated primary herpesvirus infection in children: epidemiology based on 93 non-neonatal cases, S Afr Med J 43:647, 1967. 4. Montgomerie JZ, Becroft DMO, Croxson MC, et al: Herpes simplex virus infection after renal transplant, Lancet 2:867, 1969. 5. St. Geme JW Jr, Prince JT, Burke BA, et al: Impaired cellular resistance to herpes-simplex virus in WiskottAldrich, N Engl J Med, 273:229, 1965. 6. Nishimura K, Nagamoto A, and Igarashi M: Extensive skin manifestations of herpesvirus infection in an acute leukemic child, Pediatrics 49:294, 1972. 7. Muller SA, Herrmann EC Jr, and Winkelmann RK: Herpes simplex infections in hematologic malignancies, Am J Med 52:102, 1972. 8. Bencousome SA, and Tsutsumi V: A fast method for processing biologic material for electron micros'copy, Lab Invest 23:447, 1970. 9. Knight V, Brasier F, Greenberg SB, et al: Immunofluorescent diagnosis of acute viral infection, South Med J 68:764, 1975. 10. Alford CA Jr, and Whitley RJ: Treatment of infections due to herpesvirus in humans: A critical review of the state of the art, J Infect Dis 133S:A101, 1976. 11. Ch'ien LT, Whitley RJ, Nahmias AJ, et al: Antiviral chemotherapy and neonatal Herpes simplex virus infection: a pilot study-experience with adenine arabinoside (ARAA), Pediatrics 55:678, 1975.
holic, had had eight spontaneous abortions. Of six live births, one infant died of unknown cause and two other children were small at birth and failed to attain catch-up growth. Abbreviations used: FAS: fetal alcohol syndrome BUN: blood urea nitrogen The patient's weight, height, and head circumference at birth were, respectively, 1.7 kg, 37 cm, and 27 cm. Respiratory distress was present in the neonatal period. Growth rate was very poor, and there was a significant lag in social and motor development9 Moderate proteinuria, dilute urine, mild systemic acidosis, and rising BUN and serum creatinine values were observed. The child was referred to the Medical University Hospital at the age of 26 months9 Physical examination revealed a small, microcephalic, black male. Weight was 4.9 kg, height 64 cm, and head circumference 39 cm. Blood pressure was 100/60 mm Hg. A round forehead, flattened superior orbital ridges, short palpebral fissures, ptosis of the eyelids, epicanthal folds, right esotropia, and small asymmetrical earlobes were noted (Fig 1). The nose was short and stubby with a flattened nasal bridge and upturned nares. Other abnormalities included hypoplastic nipples, limited extention of the elbows, small nails, and delayed dental age. The patient was restless and demonstrated repetitive and self-stimulating behavior9 Developmental testing indicated an overall function at a ten-month old level.
760
Brief clinical and laboratory observations
Fig. 1. The patient at 33 months of age. Laboratory studies disclosed a BUN of 38 mg/dl, serum creatinine 2.1 mg/dl, CO~ combining power 14 mEq/1. Endocrine and metabolic screening studies were unremarkable and chromosome analysis showed a normal male karyogram. Serologic and immunologic tests were within normal limits. No abnormalities were seen on computerized axial tomography of the brain. Urinalyses demonstrated specific gravities below 1.008, 2+ proteinuria by dipstick, and normal sediment. Urinary pH registered in the 6.0 to 7.0 range. Results of urine cultures were negative. Creatinine clearance did not exceed 18 ml/minute/1.73 m 2. The 24-hour urinary excretion of protein, sodium, and potassium were 250 mg, 4 mEq, and 10 mEq, respectively. Renal radioisotopic studies, intravenous pyelography, and renal sonography revealed a single, poorly functioning, hypoplastic right kidney, with a normal calyceal pattern. The voiding cystourethrogram was normal. DISCUSSION Several publications have focused attention on a distinctive pattern of abnormalities occurring in the offspring of alcoholic mothers. Jones and Smith I coined the term "fetal alcohol syndrome" to describe this constellation of peculiar features. The child in this report fits the characteristic pattern o f anomalies seen in the FAS, 2 and the mother satisfied the criteria for alcoholism as
The Journal of Pediatrics November 1977
p u b l i s h e d by the Criteria Committee, National Council on Alcoholism? Renal manifestations are not explicitly mentioned as an integral part of the FAS. However, a review of reported cases revealed several patients with urinary tract anomalies: Hanson, Jones, and Smith's series of 41 patients with the F A S included one child with unilateral hydronephrosis? However, renal evaluations were not carried out in most of their patients, which is also true for the 127 cases reported by Lemoine and co-workers, 4 who indicated that one child had a "renal malformation." Goetzman and associates, 5 on the other hand, studied the urinary tract of three infants with the FAS. Two had renal anomalies consisting of crossed fused ectopia and renal hypoplasia with uretero-pelvic junction obstruction? Tenbrinck and Buchin ~ found unilateral renal pelviectasis and superior calyectasis in their patient. In addition, a recent study on mice given alcohol during pregnancy has demonstrated a high incidence of urinary tract anomalies in the offspring. 7 The above reports and the present case indicate that renal anomalies should be included in the pattern of defects associated with the FAS. R e n a l insufficiency, which has not been reported previously, can also occur, depending on the type of anomaly encountered. These patients are at risk to develop urinary tract infections, urolithiasis, obstruction, acidosis, anemia, skeletal lesions, and uremia as additional causes of growth deficiency. The identification of renal system involvement in the FAS is important from a prognostic point of view and to permit adequate and comprehensive m a n a g e m e n t of patients with this syndrome. The authors express their gratitude to Dr. Kenneth L. Jones for his review of the case material and to Dr. Mitchell I. Rubin for his helpful comments.
REFERENCES
1. Jones KL, and Smith DW: Recognition of the fetal alcohol syndrome in early infancy, Lancet 2:999, 1973. 2. Hanson JW, Jones KL, and Smith DW: Fetal alcohol syndrome: Experience with 41 patients, JAMA 235:1458, 1976. 3. Criteria Committee, National Council on Alcoholism: Ann Intern Med 77:249, 1972. 4. Lemoine P, Harousseau H, Borteyru JP, and Menuet JC: Les enfants de parents alcooliques. Anomalies observees, Ouest Medical 25:477, 1968. 5. Goetzman BW, Kagan J, and Blankenship WJ: Expansion of the fetal alcohol syndrome, Clin Res 23:100A, 1975. 6. Tenbrinck MS, and Buchin SY: Fetal alcohol syndrome, report of a case, JAMA 232:1144, 1975. 7. Randall CL, Taylor WJ, and Walker DW: Ethanol-induced malformations in mice, Alcoholism: Clin Exp Res 1:219, 1977.
Brief clinical and laboratory observations
study by_electron microscopy, 8 fluorescent antibody techniques, ~ light microscopic examination for characteristic Cowdry type A intranuclear inclusions, and direct viral isolation procedures. Experimental trials with antiviral agents in h u m a n beings have yielded variable results; however, preliminary studies with adenosine arabinoside in the treatment of HSV infection are encouraging. 1~This c o m p o u n d may be efficacious in the treatment of HSV infection provided the drug is administered early in the course of disease. 11 Despite the prompt initiation of adenosine arabinoside therapy, the patient presented developed fulminant hepatitis and DIC. HSV type 1 was isolated from his liver and adrenal glands at death after four days of therapy. The authors express their appreciation to Dr. Steve Greenberg for typing the HSV and to Ms. L. Hartsell and K. Boyle for assistance in preparation of the manuscript.
REFERENCES 1. Nahmias A J, and Roizman G: Infection with herpessimplex viruses 1 and 2, N Engl J Med 289:667, 719, 781, 1973. 2. Nahmias A J, Alford CA, and Korones SB: Infection of the newborn with herpes virus hominis, Adv Pediatr 17:185, 1970.
Renal anomalies in the fetal alcohol syndrome Martin M. DeBeukelaer, M.D.,* Carrie L. Randall, Ph.D., Charleston, S. C., and Donna R. Stroud, M.D., Greenville, S. C.
THE PURPOSE of this report is to focus attention on the renal manifestations of the fetal alcohol syndrome, by describing renal insufficiency and anomalies of the urinary tract in a patient born to an alcoholic mother.
CASE REPORT The patient was born after a 32-week gestation and uncomplicated delivery. The 31-year-old mother, a known chronic alcoFrom the Departments of Pediatrics and Psychiatry, Medical University of South Carolina, and Greenville General Hospital. *Reprint address: Department of Pediatrics, Medical University of South Carolina, 80 Barre St., Charleston, S. C. 29401.
759
3. Kipps A, Becker W, Wainwright J, et al: Fatal disseminated primary herpesvirus infection in children: epidemiology based on 93 non-neonatal cases, S Afr Med J 43:647, 1967. 4. Montgomerie JZ, Becroft DMO, Croxson MC, et al: Herpes simplex virus infection after renal transplant, Lancet 2:867, 1969. 5. St. Geme JW Jr, Prince JT, Burke BA, et al: Impaired cellular resistance to herpes-simplex virus in WiskottAldrich, N Engl J Med, 273:229, 1965. 6. Nishimura K, Nagamoto A, and Igarashi M: Extensive skin manifestations of herpesvirus infection in an acute leukemic child, Pediatrics 49:294, 1972. 7. Muller SA, Herrmann EC Jr, and Winkelmann RK: Herpes simplex infections in hematologic malignancies, Am J Med 52:102, 1972. 8. Bencousome SA, and Tsutsumi V: A fast method for processing biologic material for electron micros'copy, Lab Invest 23:447, 1970. 9. Knight V, Brasier F, Greenberg SB, et al: Immunofluorescent diagnosis of acute viral infection, South Med J 68:764, 1975. 10. Alford CA Jr, and Whitley RJ: Treatment of infections due to herpesvirus in humans: A critical review of the state of the art, J Infect Dis 133S:A101, 1976. 11. Ch'ien LT, Whitley RJ, Nahmias AJ, et al: Antiviral chemotherapy and neonatal Herpes simplex virus infection: a pilot study-experience with adenine arabinoside (ARAA), Pediatrics 55:678, 1975.
holic, had had eight spontaneous abortions. Of six live births, one infant died of unknown cause and two other children were small at birth and failed to attain catch-up growth. Abbreviations used: FAS: fetal alcohol syndrome BUN: blood urea nitrogen The patient's weight, height, and head circumference at birth were, respectively, 1.7 kg, 37 cm, and 27 cm. Respiratory distress was present in the neonatal period. Growth rate was very poor, and there was a significant lag in social and motor development9 Moderate proteinuria, dilute urine, mild systemic acidosis, and rising BUN and serum creatinine values were observed. The child was referred to the Medical University Hospital at the age of 26 months9 Physical examination revealed a small, microcephalic, black male. Weight was 4.9 kg, height 64 cm, and head circumference 39 cm. Blood pressure was 100/60 mm Hg. A round forehead, flattened superior orbital ridges, short palpebral fissures, ptosis of the eyelids, epicanthal folds, right esotropia, and small asymmetrical earlobes were noted (Fig 1). The nose was short and stubby with a flattened nasal bridge and upturned nares. Other abnormalities included hypoplastic nipples, limited extention of the elbows, small nails, and delayed dental age. The patient was restless and demonstrated repetitive and self-stimulating behavior9 Developmental testing indicated an overall function at a ten-month old level.
760
Brief clinical and laboratory observations
Fig. 1. The patient at 33 months of age. Laboratory studies disclosed a BUN of 38 mg/dl, serum creatinine 2.1 mg/dl, CO~ combining power 14 mEq/1. Endocrine and metabolic screening studies were unremarkable and chromosome analysis showed a normal male karyogram. Serologic and immunologic tests were within normal limits. No abnormalities were seen on computerized axial tomography of the brain. Urinalyses demonstrated specific gravities below 1.008, 2+ proteinuria by dipstick, and normal sediment. Urinary pH registered in the 6.0 to 7.0 range. Results of urine cultures were negative. Creatinine clearance did not exceed 18 ml/minute/1.73 m 2. The 24-hour urinary excretion of protein, sodium, and potassium were 250 mg, 4 mEq, and 10 mEq, respectively. Renal radioisotopic studies, intravenous pyelography, and renal sonography revealed a single, poorly functioning, hypoplastic right kidney, with a normal calyceal pattern. The voiding cystourethrogram was normal. DISCUSSION Several publications have focused attention on a distinctive pattern of abnormalities occurring in the offspring of alcoholic mothers. Jones and Smith I coined the term "fetal alcohol syndrome" to describe this constellation of peculiar features. The child in this report fits the characteristic pattern o f anomalies seen in the FAS, 2 and the mother satisfied the criteria for alcoholism as
The Journal of Pediatrics November 1977
p u b l i s h e d by the Criteria Committee, National Council on Alcoholism? Renal manifestations are not explicitly mentioned as an integral part of the FAS. However, a review of reported cases revealed several patients with urinary tract anomalies: Hanson, Jones, and Smith's series of 41 patients with the F A S included one child with unilateral hydronephrosis? However, renal evaluations were not carried out in most of their patients, which is also true for the 127 cases reported by Lemoine and co-workers, 4 who indicated that one child had a "renal malformation." Goetzman and associates, 5 on the other hand, studied the urinary tract of three infants with the FAS. Two had renal anomalies consisting of crossed fused ectopia and renal hypoplasia with uretero-pelvic junction obstruction? Tenbrinck and Buchin ~ found unilateral renal pelviectasis and superior calyectasis in their patient. In addition, a recent study on mice given alcohol during pregnancy has demonstrated a high incidence of urinary tract anomalies in the offspring. 7 The above reports and the present case indicate that renal anomalies should be included in the pattern of defects associated with the FAS. R e n a l insufficiency, which has not been reported previously, can also occur, depending on the type of anomaly encountered. These patients are at risk to develop urinary tract infections, urolithiasis, obstruction, acidosis, anemia, skeletal lesions, and uremia as additional causes of growth deficiency. The identification of renal system involvement in the FAS is important from a prognostic point of view and to permit adequate and comprehensive m a n a g e m e n t of patients with this syndrome. The authors express their gratitude to Dr. Kenneth L. Jones for his review of the case material and to Dr. Mitchell I. Rubin for his helpful comments.
REFERENCES
1. Jones KL, and Smith DW: Recognition of the fetal alcohol syndrome in early infancy, Lancet 2:999, 1973. 2. Hanson JW, Jones KL, and Smith DW: Fetal alcohol syndrome: Experience with 41 patients, JAMA 235:1458, 1976. 3. Criteria Committee, National Council on Alcoholism: Ann Intern Med 77:249, 1972. 4. Lemoine P, Harousseau H, Borteyru JP, and Menuet JC: Les enfants de parents alcooliques. Anomalies observees, Ouest Medical 25:477, 1968. 5. Goetzman BW, Kagan J, and Blankenship WJ: Expansion of the fetal alcohol syndrome, Clin Res 23:100A, 1975. 6. Tenbrinck MS, and Buchin SY: Fetal alcohol syndrome, report of a case, JAMA 232:1144, 1975. 7. Randall CL, Taylor WJ, and Walker DW: Ethanol-induced malformations in mice, Alcoholism: Clin Exp Res 1:219, 1977.
