A 16-year-old male without any systemic disease went to the doctor's office to complain of occasional headaches, which started 6 months ago.

His blood pressure was 150/90.

 Laboratory results are as follow:WBC: 13400/L,Hemoglobin: 10.5mg/dl,Platelets: 243000/L,Blood Urea Nitrogen: 185,Creatinine: 2.9 mg/dL

Urine analysis: protein 3+, blood: 3+, RBC: 16-18 /LPF, granular cast: 2-3/LPF,24 h urine volume: 1400cc, 24 h Creatinine: 590 mg, 24 h protein: 998 mg, weight: 58 kgIn secondary work-up, he had a normal level of Complements.

FH: his mother and aunt’s have history of proteinuria and hematuria. They didn't have been evaluated

Microscopic scans:

Immunofluorescence study for IgG, IgA, IgM, C3c,C4c, C1q, and Albumin show No glomerular or tubular staining.

Fibrinogen highlighted cellular crescents.

Electron microscopy:

What is your diagnosis?

The correct answer:

The Diagnosis is ALPORT Syndrome

Genetic assessment:

Alport syndrome is a progressive form of hereditary nephritis that develops due to mutations in COL4A3,COL4A4, and COL4A5 genes encoding α3, α4, and α5 chains of collagen type 4 . Defects in the assembly of α chains of collagen lead to a break in the basement membrane of glomeruli, cochlea, and the base of the ocular lens. Mutation of COL4A5 with an X-linked pattern of inheritance is the most frequent form of the disease (80The other cases show mutations of COL4A3 or COL4A4 and are inherited as autosomal recessive (15%) or autosomal dominant (5%) diseases%).

Alport diagnosis criteria:

Based on the Japanese society of pediatric nephrology working group on Alport syndrome (revised in February 2015), the main criteria for diagnosis is:

the history of persistent hematuria when the patients show one or more secondary features (Type 4 collagen abnormal expression, mutations in type 4 collagen genes or specific GBM changes on Electron microscopy) or two or more accessory features (family history of kidneydisease, bilateral sensorineural  deafness, ocular abnormalities or diffuse leiomyomatosis) they can be diagnosed as Alport syndrome

Renal biopsy in Alport syndrome:

There is no specific pathology finding on light microscopy. Mesangial hypercellularity, segmental sclerosis, interstitial fibrosis, and aggregates of foam cells have been reported. The specific electron microscopy findings include irregularity of GBM thickness, lamellation and splitting of lamina densa