Cystinosis in a black child

934

B r i e f clinical and laboratory observations

6. Underwood LE, D'Ercole A J, and Van Wyk J J: Somatomedin-C and thc assessment of growth, Pediatr Clin North Am 27:771, 1980. 7. Hall K, Enberg G, Ritzen M, Svan H, Fryklund L, and Takano K: Somatomedin-A level in serum from healthy children and from children with growth hormone deficiency or delayed puberty, Acta Endocrinol 94:155, 1980. 8. D'Ercole A J, Applewhite GT, and Underwood LE: Evidence

The Journal of Pediatrics June 1982

that somatomedin is synthesized by multiple tissues in the fetus, Dev Biol 75:315, 1980 9. Atkison DR, Weidman ER, Bhaumick B, and Bala RM: Release of somatomedin-like activity by cultured Wl-38 human fibroblasts, Endocrinology 106:2006, 1980. 10. Clemmons DR, Underwood LE, and Van Wyk J J: Hormonal control of immunoreactive somatomedin production by cultured human fibroblasts, J Clin Invest 67:10, 1981.

Cystinosis in a black child Adam J. Jonas, M.D.,* and Jerry A. Schneider, M.D., La Jolla, Calif

N EPHROPATHIC CYSTINOSIS, an autosomal recessive disorder, is characterized clinically by the development of growth failure and the renal Fanconi syndrome during the first year of life. Glomerular d a m a g e is progressive, leading to renal failure by the end of the first decade of life? .2 Hypothyroidism and a subtle retinopathy are additional clinical features which may not necessarily occur in all patients. 3,4 Biochemically, m a n y body tissues, including leukocytes, liver, conjunctiva, and kidney, have markedly increased intracellular levels of the amino acid cystine? The etiology of this disorder remains obscure. A characteristic phenotype, m a r k e d by decreased pigmentation, has been associated with individuals who have the nephropathic form of cystinosis. The skin is pale and does not become pigmented on exposure to the sun? Frequently, these individuals have blond hair, sometimes in contrast to other family members. 5 W e report here the occurence of nephropathic cystinosis in a darkly pigmented, black child. CASE REPORT This child was the 3.3 kg female child of two black, unrelated parents. Infancy was uneventful until 6 months of age when she presented with growth failure, vomiting, and diarrhea. She was hospitalized periodically for acidosis and dehydration following the onset of her symptoms, and renal disease was noted by 18 months of age. Diagnosis was not achieved until cystine crystals were seen on renal biopsy when she was 2 years of age. Rickets

was observed on skeletal radiographs. She was begun on oral electrolyte therapy and vitamin D supplementation. When seen at 44 months of age, height was 74 cm and weight was 7.5 kg, both well below the third percentile. Skin and hair were both darkly pigmented, as were the skin and hair of the other, unaffected family members. Ophthalmologic examination was normal except for fine crystalline corneal and conjunctival deposits. Examination of urine revealed glycosuria, proteinuria, and gross, generalized aminoaciduria. Creatinine clearance averaged 18 ml/minute/1.73 m 2 and 24-hour protein excretion was 1.77 gin. No evidence of rickets was seen on skeletal radiographs. Serum electrolyte values were normal (receiving replacement therapy), calcium 10.1 mg/dl, phosphorus 2.9 mg/dl, BUN 9 mg/dl, and creatinine 1.2 mg/dl. Alkaline phosphatase was 148 IU/L, thyroxine 5.9 gg/dl, hematocrit 25%, and hemoglobin 7.2 gm/dl. White blood cell cystine content was 5.4 nmol/mg protein and the cystine content of her cultured skin fibroblasts was 8.2 nmol/mg protein; both values are 50 to 100 times greater than normal. DISCUSSION The patient described here has clinical and biochemical features t h a t are consistent with n e p h r o p a t h i c cystinosis. Diagnosis, however, was delayed until 2 years of age. In fact, the diagnosis of cystinosis was considered and dismissed because the patient was not C a u c a s i a n . W e believe that the diagnosis of cystinosis should be considered in any child with growth failure and the renal Fanconi syndrome, irrespective of racial background.

From the Department of Pediatrics, University of California, San Diego, School of Medicine. Supported by grants AMI8434 and RR00827 from the National Institutes of Health. A.J.J. is a recipient of National Research Service Award 5F32AM06241 from the National Institutes of Health. *Reprint address: Department of Pediatrics, University of California, San Diego. School of Medicine. La Jolla, CA 92093.

REFERENCES

1. Schneider JA, Schulman JD, and Seegmiller JE: Cystinosis and the Faneoni syndrome, in Stanbury JB, Wyngaarden JB, and Fredrickson DS, editors: Metabolic basis of inherited disease, ed 4, New York, 1978, McGraw-Hill Book Company, Inc., pp 1660-1682. 2. Broyer M, Guillot M, Gubber MC, and Habib R: Infantile

0022-3476/82/060934+02500.20/0 9 1982 The C. V. Mosby Co.

Volume 1O0 Number 6

cystinosis: A reappraisal of early and late symptoms, in Hamburger J, Crosnier J, Grunfeld J-P, and Maxwell MH, editors: Advances in nephrology, Chicago, 1981, Year Book Medical Publishers, Inc., pp 137-166. 3. Chan AM, Lynch MJG, Bailey JD, Ezrin C, and Fraser D: Hypothyroidism in cystinosis, Am J Med 48:678, 1970.

B r i e f clinical and laboratory observations

935

4. Burke JR, EI-Bishti MM, Maisey MN, and Chantler C: Hypothyroidism in children with cystinosis, Arch Dis Child 43:947, 1978. 5. Seegmiller JE: Cystinosis, in Hers HG, and Van Hoof FV, editors: Lysosomes and storage diseases, New York, 1973, Academic Press, Inc., pp 485-518.

Spontaneous resolution of multilobar atelectasis secondary to fibrinous mediastinitis Bradley E. Chipps, M.D., Shlomo Shinnar, M.D., Ph.D., Laurens R. Pickard, M.D., Darryl J. Garfinkel, M.D., and J. Alex Hailer, Jr., M.D.,* Baltimore, Md.

IDIOPATHIC FIBRINOUS MEDIASTINITIS is rarely e n c o u n t e r e d in p e d i a t r i c practice. T h e n a t u r a l history and course o f this process have been d e s c r i b e d in relatively few children. ~-6 W e have h a d a p a t i e n t with this entity who p r e s e n t e d with an extrinsic bronchial c o m p r e s s i o n causing massive m u l t i l o b a r atelectasis. CASE HISTORY A 41/2-year-old black boy was referred to The Children's Center of The Johns Hopkins Hospital for evaluation of collapse of the right middle and right lower lobes of unknown duration (Fig. 1). The patient had been in his usual state of good health until three months prior to admission when he developed a dry hacking cough. During the subsequent three months, his nonproductive cough gradually increased, especially at night. Noisy respiration, decreased activity, and elevated respiratory rate were noted in the month prior to admission. There was no history of choking or any acute febrile illness in the past six months. The review of systems was negative. His past medical history and family history were unremarkable. Physical examination revealed a tachypneic, well-nourished black boy. The only abnormal physical findings were in the thorax. The right lower lung field was dull to percussion, with no audible breath sounds. High-pitched inspiratory and expiratory rhonchi were heard just above the area of consolidation. Examination of the left lung was normal. Laboratory findings included: hemoglobin 9.4 gm/dl, hematocrit 28%, white blood cell count 11,800/mm 3 with 67% segmented neutrophils, 24% lymphocytes, 2% atypical lymphocytes, 5%

From the Departments of Pediatrics, Radiology and Radiological Science, and Surgery, The Johns Hopkins Medical Institutions. Supported in part by the Hospital for Consumptives o f Maryland (Eudowood), and the Robert E. Garrett Foundation. *Reprint address: Division of Pediatric Surgery, The Johns Hopkins Hospital, Baltimore, MD 21205.

0022-3476/82/060935+03500.30/0 9 1982 The C. V. Mosby Co.

monocytes, and 2% eosinophils. The reticulocyte count was 3.0%, platelet count 620,000/ram 3, and erythrocyte sedimentation rate 60 mm/hour. The sickle cell preparation was positive, and hemoglobin electrophoresis revealed 36% Hgb S and 1.1% Hgb F. Serum electrolyte values were within normal limits. Immunoglobulin and serum complement concentrations were normal. Delayed skin test reactions for SK-SD and intermediate PPD were negative, but histoplasmosis (1:1000 histoplasmin) skin test was positive with induration greater than 10 mm at 48 hours. Delayed skin test to candida was also positive. Serial histoplasmosis complement fixation titers showed no rise in the yeast phase reaction (1:16) over a two-month period. The anti-nuclear antibody titer was 1:40. A serologic test for syphilis (RPR) was nonreactive but the C-reactive protein was positive. Pulmonary function tests of forced expiration could not be performed by the patient. Arterial blood gas values while breathing room air were Po2 93 mm Hg, Pco2 25 mm Hg, and pH 7.50. A barium esophagram showed a 10 X 5 mm lateral out-pouching of the esophagus 1 cm above the carina. An 8 cm segment of esophagus immediately distal was displaced slightly to the left and posteriorly (Fig. 1, B). Computerized axial tomography of the thorax showed diffuse narrowing of the right mainstem bronchus without evidence of calcification (Fig. 2). Bronchoscopy of the patient under general anesthesia with a 3.8 mm fiberscope showed a smooth nonpulsatile stenosis of the bronchus intermedius. The overlying mucosa was minimally friable. There was no evidence of a foreign body or an endobrochial lesion. Distal to the stenosis, patent R M L and RLL bronchi could be seen. Forceps biopsy showed only fragments of respiratory epithelium and fibrinous debris. Cultures for bacteria, fungi, and mycobacteria were negative. Because of the unexplained narrowing of the bronchus intermedius and concern about a possible mass lesion, a right thoracotomy was performed. The RML and RLL were completely collapsed and could not be inflated with positive pressure ventilation. There was a fibrinous attachment of the superior segment of the lower lobe to the parietal pleura. A dense, white, woody mass was exposed in the right hilum and extended into the major and minor