Thin basement membrane disease overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Marufa Marium, M.B.B.S[2]
Overview
Thin basement membrane disease (TBMD) is one of the inherited disorder of kidney affecting glomeruli. It is also known as Thin basement membrane nephropathy (TBMN) or thin membrane nephropathy or thin GBM syndrome or benign familial hematuria or benign familial essential hematuria or congenital hereditary hematuria or hereditary hematuria or familial hematuric nephritis or benign hereditary nephritis. Being the most frequent cause of familial hematuria TBMD is affecting 1% of population.[1] 40% of TBMD is caused by germline mutation in COL4A3, COL4A4 genes, but female carrier with COL4A5 mutation may develop TBMD. [2]
Historical Perspective
Thin basement membrane disease is the most common cause of Persistent recurrent hematuria. A form of Benign hemorrhagic nephritis is first noted in 1926 by Goerge Baehr. ThenPersistent recurrent hematuria is first observed in seven out of eight siblings in a family by Melvin I. Marks and Keith N. Drummond in 1969. P. W. Rogers was the first one to analyse the association between recurrent asymptomatic hematuria and thin glomerular basement membrane in 1973. The association between the COL4A3, COL4A4 and COL4A5 gene mutation in long q arm of chromosome 2 and the recurrence of X-linked and autosomal alport syndrome in several studies conducted in 1990-1994. In 1996, it was demonstrated that the cause of Benign familial hematuria is Mutation in COL4A3 and COL4A4.
Classification
There is no distinctive classification on Thin basement membrane disease.
Pathophysiology
Thin basement membrane disease is usually caused by Heterozygous mutation in COL4A3 and COL4A4 gene in autosomal nonprogressive dominant pattern and heterozygous mutation in COL4A5 gene in X-chromosome may cause Thin basement membrane disease in female.. Alport syndrome, IgA nephropathy are among the most common to have association with Thin basement membrane disease. Gross pathology usually shows no distinctive features although Diffuse thinning of GBM in electron microscopy, Erythrocytes in between renal tubules ad bowman's membrane, Minimal glomerular change or mesangial expansion on light microscopy are seen on microscopic histopathological analysis.
Causes
Thin basement membrane disease is an inherited disorder caused by mutation in COL4A3, COL4A4 and rarely COL4A5 gene mutation. Some form of TBMD are due to 'De novo' mutation.
Differentiating thin basement membrane disease from Other Diseases
As a common cause of several glomerulopathies, Persistent hematuria must be differentiated as benign cause of thin basement membrane disease from other life threatening caueses of glomerular bleeding including Alport syndrome, IgA nephropathy, lupus nephritis, postinfectious glomerulonephritis.
Epidemiology and Demographics
The incidence of thin basement membrane disease is 1%-2% based on data available in 2006. The prevalence of thin basement membrane disease is 1%.Thin basement membrane disease affects children and adult equally with more predominance in female. According to available data most cases are reported in developed countries specially in Europe where majority of patient are of Caucasians race. Chinese, Indians, Africans are less commonly affected.
Risk Factors
There are no established risk factors for Thin basement membrane disease.
Screening
According to the most physicians, screening for thin basement membrane disease by Renal function test is recommended every 1-2 years among patients with Hypertension, Proteinuria, and Renal impairment. Family members of a patient with thin basement membrane disease should also be evaluated for early diagnosis of TBMD.
Natural History, Complications, and Prognosis
TBMD is may developed or found incidentally in first decade of life in symptomatic patient, may present symptoms later in third decade in asymptomatic patient. If left untreated, adult TBMD patients with proteinuria may develop hypertension, renal impairment leading to renal insufficiency. Prognosis is usually good in patient with isolated hematuria in TBMD.
Diagnosis
Diagnostic Study of Choice
Renal biopsy is the gold standard test for Thin basement membrane disease showing diffuse thinning of glomerular basement membrane, RBCs in between renal tubules ad bowman's membrane, Minimal glomerular change or mesangial expansion on light microscopy are seen on microscopic histopathological analysis.
History and Symptoms
Obtaining complete history both for the patient and family is an important aspect of diagnosing TBMD. The hallmark of TBMD is benign hematuria. A positive family history of incidental finding of intermittent or persistent hematuria is suggestive of TBMD. TBMD is mostly asymptomatic. Microscopic hematuria is found incidentally.
Physical Examination
A complete medical and family history and comprehensive renal exam must be performed to help identify and properly diagnose Thin basement membrane disease. Patient is mostly asymptomatic.
Laboratory Findings
Laboratory findings consistent with the diagnosis of TBDM include asymptomatic benign microscopic hematuria with normal renal function test.
Electrocardiogram
There are no ECG findings associated with Thin basement membrane disease.
X-ray
There are no X-ray findings associated with Thin basement membrane disease.
Echocardiography and Ultrasound
There are no echocardiography/ultrasound findings associated with thin basement membrane disease.
CT scan
There are no CT scan findings associated with thin basement membrane disease.
MRI
There are no MRI findings associated with thin basement membrane disease.
Other Imaging Findings
There are no findings associated with thin basement membrane disease in other imaging procedures.
Other Diagnostic Studies
DNA sequencing of COL4A3,COL4A4, COL4A5 is needed for differentiating TBMD and Alport syndrome in specialized laboratory.
Treatment
Medical Therapy
There is no treatment for Thin basement membrane disease; the mainstay of therapy is supportive care.
Interventions
There are no other interventions associated with thin basement membrane disease.
Surgery
There is no surgical procedure required for Thin basement membrane disease; the mainstay of therapy is supportive care.
Primary Prevention
There are no established measures for the primary prevention of TBMD as it is a hereditary disease.
Secondary Prevention
Effective measures for the secondary prevention of TBMD is Health education to patients and their family members. Patients and their family members should be educated on sign and symptoms of proteinuria, hypertension, renal dysfunction. Patient along with affected family members should be monitored regularly for the development of hypertension , persistent proteinuria and progression to renal impairment.
References
- ↑ Savige J, Rana K, Tonna S, Buzza M, Dagher H, Wang YY (October 2003). "Thin basement membrane nephropathy". Kidney Int. 64 (4): 1169–78. doi:10.1046/j.1523-1755.2003.00234.x. PMID 12969134.
- ↑ Buzza M, Wilson D, Savige J (May 2001). "Segregation of hematuria in thin basement membrane disease with haplotypes at the loci for Alport syndrome". Kidney Int. 59 (5): 1670–6. doi:10.1046/j.1523-1755.2001.0590051670.x. PMID 11318937.