Pediatr Nephrol (2004) 19:349–352 DOI 10.1007/s00467-003-1352-5
BRIEF REPORT
Janusz S´wietlin´ski · Iwona Maruniak-Chudek · Zofia I. Niemir · Aldona Woz´niak · Maria Wilin´ska · Joanna Zacharzewska
A case of atypical congenital nephrotic syndrome Received: 2 May 2002 / Revised: 29 September 2003 / Accepted: 29 September 2003 / Published online: 9 January 2004 IPNA 2004
Abstract We present a female newborn with the nephrotic syndrome of intrauterine onset and a unique set of extrarenal abnormalities, as well as atypical renal lesions. The extrarenal anomalies comprised a soft tissue hemangioma in the frontotemporal region, unilateral microphthalmia (with persistent hyperplastic corpus vitreous and detachment of the retina), and glaucoma in the other eye. Immature glomeruli and/or glomeruli with large cellular crescents were found in renal biopsy specimens in the 3rd week of life. On autopsy, 7 weeks later, diffuse mesangial sclerosis (DMS) was the predominant type of glomerular lesion. In addition, dilations of tubules, forming microcysts, as well as clusters of infiltrating cells in the interstitium, were found both in renal biopsy and autopsy specimens. Although the symptoms observed in our patient did not match any reported in association with the known forms of the congenital nephrotic syndrome (CNS), the most probable diagnosis seemed to be CNS J. S´wietlin´ski · I. Maruniak-Chudek Department of Neonatal Intensive Care, Medical University of Silesia, Katowice, Poland Z. I. Niemir Department of Nephrology, University of Medical Sciences, Poznan´, Poland A. Woz´niak Department of Pathology, University of Medical Sciences, Poznan´, Poland M. Wilin´ska · J. Zacharzewska Neonatal Intensive Care Unit, Łomz˙a, Poland I. Maruniak-Chudek ()) Klinika Intensywnej Terapii i Patologii Noworodka, Grnos´la˛skie Centrum Zdrowia Dziecka i Matki, Ul. Medykw 16, 40-752 Katowice, Poland e-mail:
[email protected] Tel.: +48-32-2071757 Fax: +48-32-2071781
due to DMS of intrauterine onset, with superimposed drug-related tubulointerstitial nephritis. Keywords Glomerular crescents · Diffuse mesangial sclerosis · Interstitial infiltrates · Hemangioma · Ocular abnormalities
Introduction Congenital nephrotic syndrome (CNS) is a relatively rare disorder that may be caused by several diseases. Among the primary forms of this disorder, the most common is the Finnish type of CNS [1, 2]. Less frequent reasons for the primary form of CNS are diffuse mesangial sclerosis (DMS) and focal-segmental glomerulosclerosis [1, 2]. These diseases differ in their clinical courses, as well as their renal pathology. Mutational analysis of the genes for nephrin, the Wilms tumor gene, podocin, and/or aactinin-4 is also useful for differentiation among these diseases [3, 4, 5, 6]. A secondary form of CNS is recognized when the syndrome develops during the course of concomitant illnesses, i.e., infections (syphilis, toxoplasmosis, cytomegalovirus, viral hepatitis, human immunodeficiency virus), syndromes of congenital malformations based on genetic disorders (XY dysgenesis of gonads), or systemic diseases (systemic lupus erythematosus, glutaric aciduria) [1, 7]. We report a patient with CNS of unknown etiology presenting with a frontotemporal soft tissue hemangioma, ocular abnormalities, and atypical lesions in the kidneys.
Case report A female with a birth weight of 2,310 g was delivered spontaneously to a young G2P2 mother at 37 weeks gestation. The placenta weighed 390 g (~17% of the newborn birth weight). The parents were unrelated and the family history was unremarkable. The pregnancy was uncomplicated, with no signs of infection. Routine screening tests for syphilis and hepatitis B were negative and the mother did not complain of any unusual symptoms during
350 Fig. 1 A–D Renal biopsy specimens, E–H autopsy specimens. A A glomerulus with a large cellular crescent (arrow) and slightly thickened Bowman’s capsule (Masson staining, magnification 800). B A glomerulus presenting a crescent with early fibrotic changes (arrow). Dilated proximal tubules are also visible (hematoxylin and eosin staining, magnification 800). C An immature glomerulus. A layer of epithelial cells on the surface of the glomerular capillary tuft (arrows) and areas of interstitial fibrosis (Masson staining, magnification 200) are visible. D Interstitial fibrosis with tubular atrophy (white arrow), massive interstitial inflammatory infiltrates (black arrow), and dilated lumens of tubules forming microcysts (asterisks, hematoxylin and eosin staining, magnification 80). E Photomicrograph of two glomeruli: on the right a glomerulus with a cellular crescent (arrow) and a small increase in mesangial matrix; in the center a glomerulus with a nearly acellular shrunken tuft [periodic acid-Schiff (PAS) staining, magnification 200]. F In the center a glomerulus with the tuft transformed into a sclerotic rounded mass. The entire tuft appears to have collapsed resulting in a “dilated” Bowman’s space (PAS staining, magnification 200x). G In the center a glomerulus showing a nearly acellular shrunken sclerotic tuft surrounded by a corona of epithelial cells (arrow). On the right and left there are dilated tubules containing eosinophilic casts (asterisks) (PAS staining, magnification 200). H On the left a dilated tubule containing a hyaline cast, on the right a moderate mononuclear interstitial infiltrate composed mainly of lymphocytes and some eosinophils (arrows) (PAS staining, magnification 800)
the pregnancy. The 5-min Apgar score was 9. On initial physical examination moderate generalized edema and a protrusion of the right eye were noticed. Laboratory tests showed leukocytosis (34.4109/l) with toxic granulation, hypoproteinemia (30.3 g/l), hypocalcemia (1.82 mmol/l), and metabolic acidosis [pH 7.298, bicarbonate (HCO3) 13.9 mmol/l]. Due to severe vomiting and edema she was transferred to the neonatal intensive care unit on the 2nd day of life. On admission, she was edematous with no dysmorphic features. Her head circumference was 31.5 cm. The
right eye was protruding with a pinhole fixed pupil and the left eye seemed to be smaller than normal. Normal first and second heart sounds and no murmur were found in the auscultation of the precordium. The arterial blood pressure was 95/70 mmHg. Peripheral pulses were palpable, but cold distal parts of extremities with a slightly prolonged refill time indicated poor perfusion. Echocardiography and X-ray of the chest were normal. Repeated biochemical analysis confirmed all features of the nephrotic syndrome: total serum protein 29.9 g/l, albumin 16.4 g/l, b-globulins 3.9 g/l, and g-
351 globulins 1.3 g/l with non-selective proteinuria (30 g/l). Serum creatinine (SCr) was 1.9 mg/dl and metabolic acidosis (pH 7.255, HCO3 14.7 mmol/l) was recorded. C-reactive protein was 2.3 mg/dl (normal value
