Volume 92 Number 6

Brief clinical and laboratoly observations

to change in posture. DuBrow et al 1~ described a tenmonth-old infant (born prematurely) who was observed to have intermittent disappearance of a PDA m u r m u r ; this was documented at cardiac catheterization to be secondary to intermittent closure of the PDA. The authors postulated that this intermittent ductal closure is related either to position or kinking or to constriction of the ductal segment adjacent to the main pulmonary artery in response to humoral factors? 5 Again, no relationship between the changing m u r m u r and change in posture was demonstrated in this patient. By contrast, the strong relationship between posture and the presence or quality of the m u u r m u r in our patients suggests that a shift of m e d i a s t i n a l structures, with consequent kinking and obstruction of the PDA, was probably responsible for this change. The presence o f a m u r m u r which changes with posture, in an asymptomatic child with a normal chest radiograph and electrocardiogram, suggests the diagnosis of venous hum. In the sitting position, increased blood flow velocity in the neck veins causes the venous hum or increases its intensity? -~ By contrast, the m u r m u r in children with a small P D A is heard in the supine position and either disappears or becomes ejection systolic in character on sitting. We feel that these findings would be of great value in differentiating these two entities. Therefore, during the clinical evaluation of any murmur, the examination should be performed both in the sitting and supine positions so that a small P D A may not be missed.

REFERENCES

4. 5.

6.

7.

8. 9.

10.

11.

12.

13.

14.

15.

1. Castle RF, and Craige E: Auscultation of the heart in infants and children, Pediatrics (Suppt) 26:51 I, I960. 2. Caceres CA, and Perry LW: The innocent murmur: A

Intermittent hypertension during sickle cell crisis Billy B, Sellers, Jr., M.D., Augusta, Ga.

SICKLE CELL DISEASE has been associated with a variety of renal sequelae including hematuria, proteinuFrom the Division of Pediatric Nephrology, Medical College of Georgia. Reprint address: CK 280, Medical College of Georgia, Augusta, GA 30901.

0022-3476/78/0692-0941500.30/0

3.

9 1978 The C. V. Mosby Co.

94 1

problem in clinical practice, ed 1, Boston, 1967, Little, Brown and Company. Fogel DH: The innocent (functional) cardiac murmur in children, Pediatrics 19:793, 1957. Walsh SZ: Functional murmurs in infants and children, Paediatrician 2:284, 1973. Dammann JF Jr, and Sell CG: Patent ductus arteriosus in the absence of continuous murmur, Circulation 6:110, 1952. Campbell M, and Hudson R: The disappearnce of continuous murmur of patent ductus arteriosus, Guys Hosp Rep 101:32, 1952. Lukas DS, Araujo J, and Steinberg I: The syndrome of patent ductus arteriosus with reversal of flow, Am J Med 17:298, 1954. Keys A, and Shapiro M J: Patency of the ductus arteriosus in adults, Am Heart J 25:158, 1943. Gross RE: The patent ductus arteriosus. Observation on diagnosis and therapy in 525 surgically treated cases, Am J Med 12:472, 1952. Crevasse LE, Logue RB: Atypical patent ductus arteriosus: The use of vasopressor agents as a diagnostic aid, Circulation 19:332, 1959. Campbell M: Patent ductus arteriousus; some notes on prognosis and pulmonary hypertension, Br Heart J 17:511, 1955. Burchell HB, Swan HJC, and Wood EH: Demonstration of differential effects on pulmonary and systemic arterial pressure by variation in oxygen content of inspired air in patients with patent ductus arteriosus and pulmonary hypertension, Circulation 8:681, 1953. Shapiro W, Said SI, and Nova PL: Intermittent disappearance of the murmur of patent ductus arteriosus, Circulation 22:226, 1960. Keith TR, and Sagarminaga J: Spontaneously disappearing murmur of patent ductus arteriosus: A case report, Circulation 26:1235, 1961. DuBrow IW, Fisher E, and Hastreiter A: Intermittent functional closure of patent ductus arteriosus in a tenmonth-old infant; hemodynamic documentation, Chest 68:110, 1975.

ria, nephrotic syndrome, urinary concentrating defects, renal infarction, and progressive renal f a i l u r e ? - ' Although renal manifestations are common, hypertension in sickle cell disease has been noted only rarely? ~ This report describes a patient with severe, intermittent hypertension occurring only during sickle cell crisis. CASE REPORT Patient A. G. is a 13-year-old black boy with sickle cell disease (95% S, 5% At hemoglobin) and significant hypertension during painful sickle cell crises. The patient had been admitted to the hospital numerous times for painful crises and had welldocumented hypertension associated with these crises for the past three years. A review of the family history revealed a sister with sickle cell disease and a vague history of hypertension in the patient's mother's family.

942

Brief clinical and laboratory observations

CLINICAL COURSE OF SICKLE CELL CRISES 200

~2.~

KEY

~

E~TEO

B~ES~U.E

~

NOnMAL

The Journal of Pediatrics June 1978

aENkN

ACT,V,TV

~.~

150

loo o< 50

DAYS IN HOSPITAL

WEEKS DAYS IN HOSPITAL AS OUTPATIENT (2 REPRESENTATIVE OF 24 TOTAL)

Fig. 1. Patient's course during two representative hospitalizations for sickle cell crisis with hypertension. A prolonged outpatient course during which time the patient was free of sickle cell crisis or hypertension is represented.

At the time of the current evaluation, the patient was admitted with a painful sickle cell crisis and had a blood pressure of 170/ 92. Oral temperature was 37.5~ respirations 34/minute, and pulse 96/minute. Positive physical findings were restricted to a Grade 2/6 systolic heart murmur heard along the left sternal border; tenderness to palpation in both upper arms and both anterior thighs; and slight tenderness to deep palpation in the abdomen and muscular areas of the flanks9 There were no abnormalities of the fundi or neurologic examination. There was no evidence of edema or circulatory congestion. Examination of the urine revealed a pH of 5.0; specific gravity 1.003; urinary protein 30 mg/dl; no glucose, ketones, or blood; and an occasional red blood cell/hpf. Urine culture had no growth at 72 hours. The blood count revealed a white blood cell count of 17,800/mm with a mild left shift, hemoglobin 8.8 gm/dl, and hematocrit 28%. Serum electrolyte values were normal. The blood urea nitrogen was 8 mg/dl and the serum creatinine concentration 0.4 mg/dl. Peripheral plasma renin activity before anti-hypertensive medication and during volume expansion was 12.2 ng/ml hour (normal for volume depletion is 0.5 to 7.0 ng/ml/ hour). Serum thyroxine concentration and 24-hour urinary excretion of vanillylmandelic acid were normal. Antinuclear antibody, serum complement, and anti-streptococcal enzyme titers were normal. Creatinine clearance was 166 ml/minute/l.73 mL Urinary protein excretion was 560 rag/24 hours9 A hypertensive excretory urogram was normal. Renal arteriogram and renal vein renin determination were not done9 The patient's course during two representative hospitalizations is illustrated in Fig. 1. DISCUSSION The patient in this report had intermittent hypertension during sickle cell crisis which was not associated with detectable anatomic or functional abnormalities in the urinary tract. This hypertension was associated with

elevated plasma renin activity and seems likely to be due to some renal phenomenon. It is postulated that this hypertension is associated with small areas of renal hypoperfusion as a result of sludging of red cells in the small vessels of the kidney. Alterations of renal blood flow in patients with sickle cell disease have been reported?. 6 Micr0radioangiographic studies have indicated that medullary blood flow is probably reduced in these patients. 7 These investigations suggest that circulatory impairment is due to occlusion of the vasorecta by sickled red blood cells. It is possible that local, transient occlusion of small vessels in the kidney could produce transient blood pressure elevations via the renin-angiotensin system. Since hypertension is rare in patients with sickle cell crises, additional factors may predispose our patient to hypertension. It is possible that a congenital anomaly of the renal vasculature could predispose this patient to an exaggerated response to the effects of segmental renal hypoperfusion. No documentation of this has been made in our patient. Several other possibilities for the etiology of hypertension in this patient exist. It is possible that the hypertension was due solely to salt and water overload. This seems unlikely in view of the studies which indicate that patients with sickle cell crisis have volume depletion ~ and that renal sodium handling has been found to be normal in patients with sickle cell disease: 9 On the other hand, volume expansion may exaggerate hypertension due to some other cause. It is also possible that the autonomic nervous system played an important role in the production of hypertension in this patient. Pain may elevate systemic blood pressure by increasing sympathetic tone and causing release of adrenergic agents. 1~ It seems unlikely that this was the sole etiology for the hypertension in this case, since the hypertension remained for several days after pain had subsided 9 Mild glomerulonephritis and segmental renal infarction are possibilities for the etiology of the hypertension, but could not be documented. REFERENCES 1. Schlitt LE, and Keitel HG: Renal manifestations of sickle cell disease: A review, Am J Med Sci 239:773, 1960. 2. Buckalew VM, and Someren A: Renal manifestations of sickle cell disease, Arch Intern Med 133:660, 1974. 3. Femi-Pearse D, and Odunjo EO: Renal cortical infarcts in sickle-cell trait, Br Med J 3:34, 1968. 4. Konotey-Ahuln FID: The sickle cell diseases, Arch Intern Med 133:611, 1974. 5. Etteldorf JN, Luttle AH, and Clayton GW: Renal function studies in pediatrics; hemodynamics in children with sickle cell anemia, Am J Dis Child 83:185, 1952.

Volume 92 Number 6

B r i e f clinical a n d laboratory observations

6. Hatch FE, Azar SH, Ainsworth TE, Nardo JM, and Culbertson JW: Renal circulatory studies in young adults with sickle cell anemia, J Lab Clin Med 76:632, 1970. 7. Statius vanEpps LW, Pinedo-Veels C, DeVries GH, and DeKonig J: Nature of the concentrating defect in sickle-cell nephropathy, Lancet 1:450, 1970. 8. Barreras L, Diggs LW, and Lipscomb A: Plasma volume in sickle cell disease, South Med J 59:456, 1966.

Classical Fanconi anemia in a family with hypoplastic anemia Frederick P. Li, M.D.,* and Nancy Upp Potter, R.N., Boston, Mass.

IN 1 947, Estren and D a m e s h e k 1 described five siblings who developed hypoplastic anemia at 6 to 10 years of age; the proband was the sole survivor. No birth defects were found in these five children or in nine other healthy siblings. The authors suggested that the patients had a genetic disease distinct from Fanconi anemia. Recent follow-up of the family slaeds new light on the diagnosis.

9. Hatch FE, Cultertson JW, and Diggs LW: .Nature of the renal concentrating defect in sickle cell disease, J Clin Invest 46:336, 1967. 10. Barron DH: The pressure gradient and pulse in the vascular system, in Ruch TC, and Fulton JF, editors: Medical physiology and biophysics, ed 19, Philadelphia, 1960, WB Saunders Company.

the thumbs and first metacarpals, webbing between the second and third toes, and retarded growth during childhood. At 10 years of age, she developed aplastic anemia. Laboratory studies showed a hemoglobin of 2.2 gm/dl, platelet count of 10,000/ mm 3, and white count of 2,300/ram 3 with 46% neutrophils, 52% lymphocytes, 1% eosinophils, and 1% monocytes. A bone marrow aspirate was hypocellular. Chromosome analysis of the peripheral blood revealed no aneuploidy, and the frequency of breaks and rearrangements was not recorded. Autopsy after a fatal subarachnoid hemorrhage showed a hypocellular marrow and one additional anomaly: incomplete fissuring of both lungs. The final diagnosis was Fanconi anemia. The father of the proband (Patient 7) developed carcinoma of the larynx at age 77 years, and his mother (Patient 4) died with colon cancer at age 84. No blood dyscrasia or cancer has developed in the nine surviving siblings of the proband (Patients 16-24) or their mother (Patient 8). The four siblings of the child with Fanconi anemia (Patients 26 to 29) are healthy except for a heart murmur in Patient 28. The family has refused additional studies. COMMENT

CASE REPORTS After the publication, the proband (Patient 15) had a complete clinical remission of hypoplastic anemia (Fig. 1). Fourteen years later (age 24), he had normal peripheral blood-counts at the time of hospitalization for pleurisy. However, he developed cough, weight loss, and intermittent hemoptysis at 28 years of age. The platelet count was 18,000/mm 3, and the other peripheral blood counts were normal. The patient did not respond to corticosteroid therapy, and died one month later with pneumonia and pulmonary hemorrhage. The bone marrow at autopsy showed almost no megakaryocytes and slight diminution of other cellular elements. A child (Patient 25) in the paternal side of the family developed aplastic anemia in 1968. Her parents were second cousins; the child's coefficient of inbreeding is 0.016. In addition, each parent was a cousin of the five siblings with hypoplastic anemia. Born at term, the child's weight (2.1 kg) and length (46 cm) were below the third percentile, and head circumference (33 cm) was below the tenth percentile. She had bilateral absence of From the Clinical Epidemiology Branch, National Cancer Institute; and the Sidney Farber Cancer Institute. Supported in part by the Amy Potter Fund. *Reprint requests: 35 Binney St., Boston, MA. 02115.

0022-3476/78/0692-0943500.20/0

943

9 1978 The C. V. Mosby Co.

Several studies have described constitutional aplastic anemia as a heterogeneous group o f pancytopenias in childhood.2. 3 This diagnosis encompasses the following clinical conditions: (1) classical Fanconi anemia with associated birth defects, (2) congenital amegakaryocytic thrombocytopenia with pancytopenia later in childhood, and (3) familial hypoplastic anemia without demonstrable congenital anomalies? -~ The present family has been cited frequently as an example of the last condition? -7 However, the new data on this family suggest that the affected siblings carried at least one gene for Fanconi anemia. The homozygous state for Fanconi anemia in Patient 25 is very likely due to inbreeding. U n d e r this assumption, the probability of carrying a gene for Fanconi anemia would be 1.0 in Patients 3 to 6, and 0.5 in the father of the siblings (Patient 7). Furthermore, hypoplastic anemia in five of the 14 siblings could be explained by inheritance of this gene, and an additional defect from the mother (Patient 8). Maternal influences may have limited gene expression in the siblings to the hematologic component of the syndrome. Alternatively, the maternal gene may be

Intermittent hypertension during sickle cell crisis.

Volume 92 Number 6 Brief clinical and laboratoly observations to change in posture. DuBrow et al 1~ described a tenmonth-old infant (born prematurel...
290KB Sizes 0 Downloads 0 Views