Early Diagnosis And Clinical Characteristics Of X Linkage Alport Syndrome In Puyang Area,Henan Province

ObjectiveAlport syndrome(AS)is a hereditary disorder,also named ocular-acoustic-kidney syndrome.The pathogenic genes are COL4A3,COL4A4,COL4A5,and COL4A6,coorperatively encoding the collagen Ⅳ.The clinical manifestations are renal insufficiency,hematuria,eye problems and dysaudia[1-2].The pathogenesis of X-linked Alport is associated with COL4A5,which is the commonest presentation.The typical clinical characteristics are family history of kidney insufficiency,proteinuria,hematuria,eye problems and dysaudia.However,minor patients only present with proteinuria and microscopic hematuria.Patients from different countries have different clinical manifestations.In China,the clinical presentations of Alport syndrome are early-onset severe proteinuria,high frequency of eye problem and dysaudia.Therefore,diverse screening methods are required for patients from different districts.To set up the clinical data bank of Alport syndrome from different areas of our country and collaborate the data is very important to the prevention,treatment and research of Alport syndrome.The commonest and main characteristic of AS in early stage is continuous twisted microscopic hematuria.Urinary red cell morphology examination is the most basic and the most commonly used method for diagnosis and differential diagnosis of Phase-contrast microscope is a classical method recognized by observing the morphology of urinary red cell at present,which in the basic hospitals is difficult to build up.The urine routine screening and ordinary optical microscope has been popularized in the primary hospital,which are simple and easy.To the early discovery and diagnosis of XLAS families,and to analyze their clinical characteristics.The gene analysis is the main methods for AS.Renal biopsy is helpful to the screening of gene,which is traumatogenic and rejected by parents.Skin biopsy and fluorescent in situ hybridization can substitute renal biopsy in gene-analysis.MethodsFor outpatient and inpatient children with AS-like manifestations,urine red blood cells were found in urine routine examination.Urine tests review once or twice in one week.If the result is still positive of hematuria,the morning fresh urine was taken,centrifugated for 10 min,and removed the supernatant.And observe the urinary sediment red cell morphology under light microscope.The severe deformation of red blood cells is the demonstration of renal hematuria.If the urine of parents are abnormal,family history should be surveyed.Those diagnosed as X-linked dominant inheritance of glomerular hematuria probands,should take routine biochemical,liver and kidney function,abdominal ultrasound,Department of Ophthalmology,slit lamp,high frequency audiometry examination and family survey,and to detect hematuria immediate family members of the above check check.To have a family history of hematuria and renal failure,part of a family member of deafness or abnormal vision,the proband carried out skin biopsy,immunofluorescence examination of type Ⅳ collagen A3~5,COL4A4 chain dyeing or application of COL4A5 and COL4A3 gene exon trapping,detection of COL4A3 second generation sequencing technology to 5 gene mutation.Eight probands and their relatives had abnormal skin or glomerular basement membrane collagen type Ⅳ.The collagen type Ⅳ showed a continuous linear distribution,the intensity of staining of collagen type Ⅳ chain A5 + + + +,negative staining intensity distribution,male patients were,but renal insufficiency time difference,since 14 ~ 70 years old is not a part of the family;male patients with renal insufficiency occurred in 2 to 10 years before the onset of hearing loss.ResultThrough the urine routine examination combined with ordinary optical microscope,eight patients with renal hematuria were identified.Urine screening and urinary red cell morphology of parents demonstrated family history of X-linked dominant hematuria.Eight probands and relatives had skin or glomerular basement membrane collagen type Ⅳ detection of abnormal.The visible collagen type Ⅳ showed a continuous linear distribution,the intensity of staining of collagen type Ⅳ chain A5 + + + +,negative staining intensity distribution.Women with staining intensity were-~ + +,only a few at the age of 60 after renal insufficiency,no significant hearing loss and decreased visual acuity in patients.In the detection of COL4A5 gene mutation in 6 families,respectively located in the Exon23:c.1561G>A(p.G521S)、Exon26:c.2014G>A(p.G672S),Exon37:c.3319G>A(p.G1107R),Exon39:c.3479dupC(p.Gly1161Argfs*23);Exon42:c.4023C>T(p.G1342R)and Exon48:c.4687C>T(p.R1563X).c.3479dupC(p.Gly1161Argfs*23)and c.4687C>T(p.R1563X)The clinical manifestations of the patients with family heavier,male patients with renal insufficiency before the age of 30.c.4023C>T(p.G1342R)Mutants in patients with clinical manifestations of the light;c.1561G>A(p.G521S)Mutations in pedigrees are currently more than 30 years old,with normal renal function;c.2014 G > A(P.G672S)mutants in patients with renal insufficiency under the age of 20.The specific mechanisms need to be further discussed.Conclusion1、The urine routine combined with ordinary optical microscope of urinary red cell examination can be used to early detection and diagnosis of the AS family,which can be applied in primary hospitals,and enrich the clinical pathological data of the region with AS.2、In this study,six with COL4A5 gene mutation were identified,and were associated with X-linked dominant inheritance.Two novel mutations are discovered.3、Clinical patients with abnormal urine test,the implementation of skin biopsy or kidney tissue type Ⅳ collagen detection in XLAS diagnosis has important significance.3、For the patients with abnormal urine test,The test for the type Ⅳ collagen by skin or renal biopsy is very essential to the diagnosis of XLAS.