|Year : 2021 | Volume
| Issue : 2 | Page : 109-111
Diffuse mesangial sclerosis: A case report of rare cause of infantile nephrotic syndrome
Tahfim Ahmed, Nusrat Jahan, Syed Saimul Huque
Department of Paediatric Nephrology, Bangabandhu Sheikh Mujib Medical University Hospital, Dhaka, Bangladesh
|Date of Submission||27-Oct-2021|
|Date of Acceptance||30-Oct-2021|
|Date of Web Publication||28-Feb-2022|
Dr. Syed Saimul Huque
Department of Paediatric Nephrology, Bangabandhu Sheikh Mujib Medical University Hospital, Dhaka 1000,
Source of Support: None, Conflict of Interest: None
Diffuse mesangial sclerosis (DMS) is a histopathological finding of a few percentages of children presented with nephrotic syndrome (NS) in the first or second decade of life. It can be an isolated finding or can be associated with some syndrome. Here we report one case of DMS presenting in the first year of life who had a fatal outcome. Early detection of this disease is necessary to draft a management plan and counseling regarding prognosis.
Keywords: Diffuse mesangial sclerosis, genetics, infantile nephrotic syndrome, renal biopsy
|How to cite this article:|
Ahmed T, Jahan N, Huque SS. Diffuse mesangial sclerosis: A case report of rare cause of infantile nephrotic syndrome. Paediatr Nephrol J Bangladesh 2021;6:109-11
|How to cite this URL:|
Ahmed T, Jahan N, Huque SS. Diffuse mesangial sclerosis: A case report of rare cause of infantile nephrotic syndrome. Paediatr Nephrol J Bangladesh [serial online] 2021 [cited 2022 May 27];6:109-11. Available from: http://www.pnjb-online.org/text.asp?2021/6/2/109/338567
| Introduction|| |
Diffuse mesangial sclerosis (DMS) is a histopathological finding of congenital and infantile nephrotic syndrome (NS). It is associated with genetic alteration and progresses to end-stage renal disease very early. It can present isolated or is associated with other syndromes such as Wilms’ tumor, aniridia, genitourinary anomalies and mental retardation (WAGR syndrome), Denys–Drash syndrome, Frasier syndrome, Pierson syndrome, or Galloway–Mowat syndrome. DMS is characterized by mesangial matrix expansion with no mesangial hypercellularity, thickened basement membrane, diminished patency of capillary lumen and hypertrophy, and vacuolization of podocytes that surround the glomerular tuft like a crown. Electron microscopy shows extensive foot process effacement without deposit but increases collagen in the mesangial cell. Genetic mutations of WT1 and PLCE1 are found in DMS.,, Here we report one case of DMS presenting in the first year of life who had a fatal outcome.
| Case Report|| |
An 11-month-old female child, second issue of her nonconsanguineous parents visited a local physician with generalized body swelling for 22 days along with the passage of loose stool for 3 days. Swelling first appeared on the face and periorbital region, then became generalized over time. The child was born at term via normal vaginal delivery at home to a 24-year-old healthy mother. Milestones were normal for her age. On physical examination, she was edematous, hypertensive, and bedside urinary albumin was 3+. She had microcephaly, anthropometrically well thrived, and external genitalia was normal. Other findings of the examination were within normal limits. Routine urine examination showed 4+ albuminuria, and renal function was normal (serum creatinine was 0.3 mg/dL). The child was treated with six doses of IV methylprednisolone (30 mg/kg). After 2 weeks, the child was referred to a nephrologist with anarasca and oliguria. Urine examinations revealed 3+ albuminuria, urinary protein creatinine ratio was in nephrotic range (57.37), and hypoalbuminemia (serum albumin 7 g/L) and hypercholesterolemia were present (serum cholesterol 386 mg/dL). Complete blood count was normal, and viral markers (HBsAg, anti-HCV, and TORCH panel) were negative. Ultrasonogram (USG) of kidney, ureter, and urinary bladder revealed that both kidneys were of normal size (right kidney 6.9 cm and left kidney 7 cm) and shape with increased cortical echogenicity and loss of corticomedullary differentiation.
Renal biopsy revealed nine mildly enlarged glomeruli with one global sclerosis with increased matrix and increased cellularity, mildly thick basement membrane, segmental mesangial solidification, and podocyte proliferation. Tubule showed hyaline cast and some cystical dilatation. Interstitium is mildly edematous with focal inflammation. Blood vessels appeared unremarkable. Immunofluorescence showed deposition of IgM (1+) and C3 in the granular pattern.
The child was treated with tacrolimus and repeated human albumin infusion.
After 1 month, she passed away at home due to sepsis.
| Discussion|| |
DMS was first described by Habib and Bois. It is a histopathological finding in some children presented with congenital or infantile nephritic syndrome. Some variants of congenital or infantile nephritic syndrome may achieve remission spontaneously or with immunosuppressive therapy, but it is a progressive disease with a fatal outcome. For this reason, management of such illness is very difficult. Management modality includes antiproteinuric measures. Surgical nephrectomy may be needed in nonresponders or to mitigate complications. Peritoneal dialysis and renal transplantation are other management options.
DMS can be an isolated presentation or can be syndromic. WAGR syndrome (Wilms’ tumor, aniridia, genitourinary anomalies, and mental retardation), Denys–Drash syndrome (NS, male gonadal dysgenesis, and Wilms tumor), Frasier syndrome (NS, normal female external genitalia, streak gonads, and XY karyotype), Pierson syndrome (NS with microconia), and Galloway–Mowat syndrome (NS, microcephaly, gyral abnormalities, and hiatal hernia) can be associated with DMS.,, Acquired cytomegalovirus infection is also linked to the causation of DMS.
Three genes have been linked with DMS: WT1 gene, PLCE1 gene, and LAMB2 gene., All of them can cause isolated DMS. In addition, mutation in WT1 gene causes Denys–Drash syndrome and Frasier syndrome, and mutation in LAMB2 gene causes Pierson syndrome. Gbadegesin et al. analyzed a worldwide cohort of 1368 children with NS and detected PLCE1 mutation as the most frequent (28.6%) and WT1 mutation as the second most frequent (8.5%) cause of isolated DMS.
Most of the patients with DMS present within 1 year of life but can also be present in the second decade. Our patient presented at 11 months of age with nephritic syndrome, without extrarenal involvement, and without renal insufficiency. USG revealed normal-size and -shaped kidneys with increased cortical echogenicity and loss of corticomedullary differentiation. Histopathology revealed [Figure 1] characteristic findings of DMS. Family history and screening of family members were not available.
|Figure 1: (A) Cystically dilated tubules. (B) Moderate mesangial expansion (green star) and podocyte proliferation (black arrow). (C) Segmental mesangial solidification (green star)|
Click here to view
Histopathological findings of DMS are pathognomonic. Collapsing variant of focal segmental glomerulosclerosis (FSGS-Col) is a differential diagnosis. FSGS-Col is a focal change characterized by hyperplasia of podocytes, collapse of underlying tufts, and tubular microcyst formation. As there was no extrarenal involvement, our case is most likely isolated DMS. Genetic analysis of WT1, PLCE1, and LAMB2 would have given more information about the disease.
| Conclusion|| |
Early recognition of this entity can modify management as well as counseling regarding prognosis. NS presented in the first year of life having a family history and rapidly deteriorating renal function is highly suspicious for DMS. Implementation of genetic study is essential to diagnose these sorts of diseases.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Habib R, Gubler MC, Antignac C, Loirat C, Gangnadoux MF [Congenital or childhood nephrotic syndrome with diffuse mesangial sclerosis]. Ann Pediatr (Paris) 1990;37:73-7.
Cohen AH, Turner MC Kidney in Galloway-Mowat Syndrome: Clinical spectrum with description of pathology. Kidney Int 1994;45:1407-15.
Gbadegesin R, Hinkes BG, Hoskins BE, Vlangos CN, Heeringa SF, Liu J, et al
. Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS). Nephrol Dial Transplant 2008;23:1291-7.
Koziell A, Grundy R Frasier and Denys-Drash syndromes: Different disorders or part of a spectrum? Arch Dis Child 1999;81:365-9.
Habib R, Bois E [Heterogeneity of early onset nephrotic syndromes in infants (nephrotic syndrome “in infants”): Anatomical, clinical and genetic study of 37 cases]. Helv Paediatr Acta 1973;28:91-107.
Haws RM, Weinberg AG, Baum M Spontaneous remission of congenital nephrotic syndrome: A case report and review of the literature. Pediatr Nephrol 1992;6:82-4.
Hu M, Zhang GY, Arbuckle S, Graf N, Shun A, Silink M, et al
. Prophylactic bilateral nephrectomies in two paediatric patients with missense mutations in the WT1 gene. Nephrol Dial Transplant 2004;19:223-6.
Besbas N, Bayrakci US, Kale G, Cengiz AB, Akcoren Z, Akinci D, et al
. Cytomegalovirus-related congenital nephrotic syndrome with diffuse mesangial sclerosis. Pediatr Nephrol 2006;21:740-2.
Lane JC Diffuse mesangial sclerosis. AJKDblog, Atlas of renal pathology2015.
Benoit G, Machuca E, Antignac C Hereditary nephrotic syndrome: A systematic approach for genetic testing and a review of associated podocyte gene mutations. Pediatr Nephrol 2010;25:1621-32.
Vankalakunti M, Jha PK, Madraki RM, Siddini V, Babu K, Ballal SH Diffuse mesangial sclerosis: Report of two cases. Indian J Nephrol 2012;22:213-6.
Albaqumi M, Barisoni L Current views on collapsing glomerulopathy. J Am Soc Nephrol 2008;19:1276-81.