A female patient with “Aase syndrome”

A female patient with “Aase syndrome”

Volume 91 Number 5 elevated. ~ In all of our patients with premature thelarche, basal LH and FSH levels were normal for age as were their responses t...

821KB Sizes 8 Downloads 119 Views

Volume 91 Number 5

elevated. ~ In all of our patients with premature thelarche, basal LH and FSH levels were normal for age as were their responses to LH-RH; these observations are in agreement with those of Reiter and associates. ~ Job and associates, however, reported pubertal LH responses in some patients with premature thelarche and suggested that this may represent an early phase of precocious puberty. Ours and previous reports indicate that these subjects do have a normal regulation of their hypothalamo-pituitary-gonadal axis. No data concerning PRL secretion in girls with premature thelarche were previously reported. The present study shows a normal PRL secretion in basal conditions and in response to TRH in girls with premature thelarche. Prolactin does not seem to play a major role in the genesis of isolated breast development in prepubertal girls. The etiologic factors involved in premature thelarche have still to be determined. The authors gratefully acknowledge the technical help of Mr. A. Van Meenen and Mrs. A~ Michaux-DuchSne and J. DelogneDesnoeck; the NIAMDD (National Institutes of Health, Bethesda, Md.) for gift of the reagents used for FSH radioimmunoassays; Dr. G.D. Niswender (Fort Collins, Colo.) for gift of the ovine reagents used for human PRL radioimmunoassays; the secretarial work of Mrs. A. M. Pauwels and helpful advice of Dr. P. Malvaux in preparing the manuscript. REFERENCES 1. Wilkins L, Blizzard RM, and Migeon CJ: The diagIlosisand treatment of endocrine disorders in childhood and adolescence, ed 3, Springfield, I11., 1965, Charles C Thomas, Publisher, pp 206-207. 2. Jenner MR, Kelch RP, Kaplan SL, and Grumbach MM: Hormonal changes in puberty: IV. Plasma estradiol, LH, and FSH in prepubertal children, pubertal females, and in

A female patient with "'Aase syndrome" M. van Weel-Sipman, M.D., J. J. P. van de Kamp, M.D., and J. de Koning, M.D., Leiden, The Netherlands D I s o RD ER S of the hematopoietic system combined with upper limb malformations occur in two well-defined syndromes: aplastic anemia of the Fanconi type I and the From the Department of Pediatrics, University Hospital, and Institute for Anthropogenetics, University of Leiden. *Reprint address: Department of Pediatrics, University Hospital Leiden, The Netherlands.

Brief clinical and laboratory observations

3.

4.

5.

6.

7.

8.

9.

10.

11.

753

precocious puberty, premature thelarche, hypogonadism, and in a child with a feminizing ovarian tumor, J Clin Endocrinol Metab 34:521, 1972. Job JC, Guilhaume B, Chaussain JL, and Garnier PE: Le drveloppement prrmatur6 isol6 des seins chez les fillettes, Arch Fr Prdiatr 32:39, 1975. Escobar ME, Rivarola MA, and Bergada C: Plasma concentration of estradiol-17fl in premature thelarche and in different types of sexual precocity, Acta Endocrinol 81:351, 1976. Radfar N, Richards C, Brych M, and Kenny FM: Percentage of dialyzable estradiol 17fl from birth to adulthood and in sexual precocity and premature thelarche, Pediatr Res 8:373, 1974. Kenny FM, Midgley AR, Jaffe RB, Garces LY, Vasquez A, and Taylot FH: Radioimmunoassayable serum LH and FSH in girls with sexual precocity, premature thelarche and adrenarche, J Clin Endocrinol Metab 29:1272, 1969. Guyda HJ, Johanson AJ, Migeon CJ, and Blizzard RM: Determination of serum luteinizing hormone (SLH) by radioimmunoassay in disorders of adolescent sexual development, Pediatr Res 3:538, 1969. Reiter EO, Kaplan SL, Conte FA, and Grumbach MM: Responsivity of pituitary gonadotropins to luteinizing hormone-releasing factor in idiopathic-precocious puberty, precocious thelarche, precocious adrenarche and in patients treated with medroxyprogesterone acetate, Pediatr Res 9:111, 1975. Robyn C, L'Hermite M, Petrusz P, and Diczfalusy E: Potency estimates of human gonadotrophins by a bioassay and three immunoassay methods, Acta Endocrinol 67:417, 1971. L'Hermite M, and Midgley AR: Radioimmunoassay of human follicle-stimulating hormone with antisera to the ovine hormone, J Clin Endocrinol Metab 33:68, 1971. L'Hermite M, Delvoye P, Nokin J, Vekemans M, and Robyn C: Human prolactin secretion, as studied by radioimmunoassay: some aspects of its regulation, in Boyns A R, and Griffiths K, editors: Prolactin and carcinogenesis, Cardiff, 1972, Alpha Omega Alpha, pp 81-97.

thrombocytopenia-absent radius syndrome? In 1969 Aase and Smith 3 described a syndrome of congenital hypoplastic anemia with bilateral triphalangeal thumbs occurring in two brothers. Other patients were described by Murphy and LubinJ by Jones and Thompson, 5 and by Terheggen. 6 Since all of these patients were males, Xlinked inheritance has been suggested. 6 However, Harvey 7 Abbreviations used TAR: thrombocytopenia-absent radius CFUC: colony forming units in culture described a girl with congenital hypoplastic anemia and bilateral triphalangeal thumbs, and Diamond and associates ~ mentioned a girl with an extra phalanx in one thumb in their survey of congenital hypoplastic anemia. In this report we describe another female patient, which makes X-linked inheritance unlikely.

754

Brief clinical and laboratory observations

Fig. 1. The patient's left hand. The triphalangeal thumb was bilaterally symmetric.

CASE REPORT The girl was born at term following an uneventful pregnancy with a birth weight of 3,500 gin. At the age of three weeks she was admitted to another hospital because of chronic diarrhea and retarded growth. She was found to have severe anemia and required several blood transfusions. At the age of three months treatment with corticosieroids was started. One month later she was referred to our hospital for further investigation. At admission she was pale and had a length of 62 cm (tenth to fiftieth percentile), a weight of 4,900 gm ( < tenth percentile), and a skull circumference of 40.2 cm (normal for age). Two incisor teeth were present. The shoulders were narrow. On both hands opposable fingerlike thumbs were seen (Fig. 1). A systolic murmur could be heard over the left precordial area. The liver and spleen were not enlarged. The family history was negative for hematologic diseases, hand deformities, and congenital heart disease. The parents and her only brother were healthy. Consanguinity was denied. Laboratory results. Hematologic values were as follows: Hemoglobin 4.9 gm/dl; hematocrit 15%; red cell count 2.9 • l0"/mm:'; reticulocytes 250100; mean corpuscular hemoglobin 32; mean corpuscular volume 100; mean corpuscular hemoglobin concentration 31. White cell count was 12,000/mm ~ and platelet count 860,000/ mm 3. Red cell morphology was normal. Serum iron concentration was 43.0 ~tmol/1. The results of the direct Coombs test was

The Journal of Pediatrics November 1977 negative; haptoglobin concentration was 50 mg/dl; hemoglobin F was 3.6% and glucose-6-phosphate was normal; no abnormal hemoglobins were present. Serum values for folic acid and vitamin BI~ were within the normal range. The erythropoiesis seen in bone marrow smears was decreased without evidence of a maturation arrest, but precursors of the other cell types were present at normal frequencies. The culture of the hematopoietic stem cells with the fibroblast layer technique showed a normal pattern (Radiobiological Institute, T.N.O. Rijswijk). Chromosome studies. Chromosome studies on bone marrow and cultered lymphocytes showed a normal 46,XX karyotype without breakages or gaps (Cytogenetic Department, Human Genetics Institute). Radiologie findings. X-ray studies of the hands showed triphalangeal thumbs. The radius on both sides was normal and there was no synostosis. Radiographs of the chest, skull, and spine ,howed no apparent abnormalities. Cardiologicfindings. An electrocardiogram revealed increased left ventricular activity, thought to be compatible with the severe anemia. There were no signs of a congenital heart defect. Dermatoglyphies. Dermatoglyphic analysis showed a normal pattern. Clinical course. The severe anemia at admission prompted treatment with a series of transfusions with leukocyte-poor erythrocyte suspensions. The continuation of the prednisone therapy resulted in a stabilization of the hemoglobin content by the age of 6.5 months. Occasionally during this time high platelet levels were found (up to 1.4 x 106/mm3). The response to steroid therapy in this patient, however, proved later on to be less satisfactory than in most of the patients described formerly. Even on appropriate prednisone therapy, she needed repeated blood transfusions at the age of 12 months. DISCUSSION T h e c o m b i n a t i o n o f congenital hypoplastic a n e m i a a n d t r i p h a l a n g e a l t h u m b s , as o b s e r v e d in this patient, appears to correspond to t h e s y n d r o m e first described by Aase a n d Smith. F a n c o n i a n e m i a can b e excluded because of the erythroid type a n e m i a , the n o r m a l C F U C a n d the n o r m a l c h r o m o s o m e pattern. Moreover, in this s y n d r o m e absence o f the radius is typical a n d f r e q u e n t l y o t h e r anomalies are present. In the T A R s y n d r o m e t h r o m b o c y t o p e n i a a n d absent radius are the most essential features, again unlike the findings in o u r patient. T r i p h a l a n g e a l t h u m b s a n d small sloping shoulders are also seen in the H o l t - O r a m s y n d r o m e ? In this syndrome, however, the u p p e r limb anomalies are c o m b i n e d with congenital h e a r t disease. F a n c o n i a n d T A R s y n d r o m e s are accepted autosomal recessive entities. TM T h e occurrence o f Aase s y n d r o m e in a female patient also suggests a u t o s o m a l recessive inheritance as a possible etiology for this h e m a t o l o g i c - u p p e r l i m b deformity syndrome. Insufficient cases of the s y n d r o m e h a v e yet b e e n studied, however, to d e t e r m i n e

Volume 91 Number 5

Brief cfinical and laboratory observations

whether there is more than one type o f genetic cause for the phenotypes corresponding to the Aase syndrome. SUMMARY

4.

A girl with congenital hypoplastic anemia and triphalangeal thumbs (Aase syndrome) is described. This is the second report o f these features is a female patient, making autosomal recessive inheritance a probable explanation. We thank Dr. J. Drukker who referred the patient to our hospital; Dr. K.A. Dicke, Radiobiological Institute, T.N.O. Rijswijk, The Netherlands, for performing the CFUC; and Dr. P.I. Pearson, Human Genetics Institute, Leiden, for the chromosome studies in our patient.

5. 6. 7. 8.

9.

REFERENCES 1. Fanconi G: Familial constitutional panmyelocytopathy Fanconi's anemia, Semin Hematol 4:233, 1967. 2. Hall J, Levin J, Kuhn J, Ottenheimer E, van Berkum P, and

Continuous intravenous insulin therapy in severe diabetic ketoacidosis: Variations in dosage requirements Marc E. Weber, M.D., and Val Abbassi, M.D.,*

3.

Washington, D. C.

C O N T I N U O U S INTRAVENOUS I N F U S I O N of low doses of insulin (0.1 U / k g / h o u r ) has been successfully employed in the treatment of diabetic ketoacidosis in children. Experience has been limited, however, and further trials are required prior to adoption o f this approach as a routine method of therapy. The purpose of this communication is to report on two children who presented with severe diabetic ketoacidosis, but who did not respond to low-dose insulin infusion therapy as it is presently recommended. CASE REPORTS

Case 1. Patient M.H., a 73A-year-old boy, was admitted to Georgetown University Hospital with a two-week history of From the Department of Pediatrics, Georgetown University School of Medicine. *Reprint address: Department of Pediatrics, Georgetown University Hospital, 3800 Reservoir Road, N. V~, Washington, DC 2000Z

10.

755

Mckusick VA: Thrombocytopenia with absent radius (TAR), Medicine 48:411, 1969. Aase JM, and Smith DW: Congenital anemia and triphalangeal thumbs: a new syndrome, J PEDIATR74:471, 1969. Murphy S, and Lubin B: Triphalangeal thumbs and congenital erythroid hypoplasia: report of a case with unusual features, J PEDIATR81:987, 1972. Jones B, and Thompson H: Triphalangeal thumbs associated with hypoplastic anemie, Pediatrics 52:609, 1973. Terheggen HG: Hypoplastische Anemie mit dreigliedrigen Daumen, Kinderheilkd 118:71, 1974. Harvey DR: Congenital hypoplastic anemia, Proc. R Soc Med 59:490, 1966. Diamond LK, Allen DM, and Magill FB: Congenital (erythroid) hypoptasfic anemia, Am J Dis Child 102:403, 196I. Holt M, and Oram S: Familial heart disease with skeletal malformations, Br Heart J 22:236, 1960. McKusick VA: Mendelian inheritance in man, ed 4, Baltimore, 1975, John Hopkins University Press.

polyphagia, polydipsia~ polyuria, weight loss, and increasing lethargy. Initial physical examination revealed a markedly dehydrated child, responsive only to pain. Respirations were Kussmaul in character. Blood pressure was 80/60 mm Hg. There was no evidence of papilledema or underlying infectious process. Laboratory data were as follows: pH 7.10; serum bicarbonate, 3.8 mmol/l; serum acetone positive at a 1:8 dilution; blood glucose, 630 mg/dl (Fig. 1); venous potassium, 5.4 mEq/l. Parenteral fluid therapy with 0.45% sodium chloride solution containing 40 mEq/1 potassium chloride and 25 mEq/l sodium bicarbonate was begun to replace calculated fluid and electrolyte deficits. A bolus injection of regular insulin, 0.1 U/kg, followed by a constant intravenous infusion at a rate of 0.1 U/kg/hour was administered. After five hours of therapy the blood glucose was 552 mg/dl; pH, 7.24; serum bicarbonate, 2.8 mmol/l; and potassium, 5.8 mEq/1. Insulin infusion was increased to 0.2 U/kg/hour, followed by a decline in the blood glucose value to 330 mg/dl within 60 minutes. There was, subsequently, a rapid improvement in other blood chemical values and in the clinical status; the rate of insulin infusion was adjusted for further declines in the blood glucose concentrations.

See related article, p. 701. Case 2. Patient D.B., an ll-year-old girl, was transferred to Georgetown University Hospital with a diagnosis of severe diabetic ketoacidosis. She had been hospitalized for the previous 24 hours at another institution, but because of a delay in the diagnosis, initial therapy had consisted of intravenous 5% dextrose and 0.33% sodium chloride solution, and multiple bolus intravenous infusions of sodium bicarbonate for metabolic acidosis. Five hours prior to transfer the diagnosis of diabetes mellitus had been made; 14 units of regular insulin intravenously and 28 units subcutaneously were administered, and parenteral therapy