ADAS varies from an asymptomatic disease (mostly presenting as a familial benign hematuria) to AD forms of proteinuria and focal segmental glomerulosclerosis (in cases without hematuria or not as a first line presentation). [orpha.net]

If a male patient does not present with hematuria during the first decade of life, he is unlikely to have Alport syndrome. [emedicine.medscape.com]

A number of patients present to nephrologists with end-stage renal failure of unknown cause and many have small kidneys, making renal biopsy inadvisable. [ncbi.nlm.nih.gov]

Moreover, leiomyomatosis and vascular abnormalities may also be present as atypical presentations. [pubmed.ncbi.nlm.nih.gov]

• Family History of Deafness

  Two patients with recurrent haematuria but no family history of deafness or haematuria showed similar extensive changes and are regarded as new mutant cases of hereditary nephritis. [ncbi.nlm.nih.gov]

• Progressive Dysphagia

  Clinical symptoms commonly include progressive dysphagia, vomiting, or dyspepsia; less frequent, retrosternal pains, dyspnea, cough, or weight loss. [frontiersin.org]

• Hypertension

  Complications Nephritic syndrome: oedema, hypertension, uraemia and oliguria. Nephrotic syndrome : oedema, hypoalbuminaemia, hyperlipidaemia. [patient.info]

  Thus, the use of ACE inhibitors is reasonable in patients with Alport syndrome who have proteinuria with or without hypertension; the same is true for angiotensin-receptor blockers (ARBs). [emedicine.medscape.com]

  Abstract A 14-year-old boy with persistent proteinuria (1.6-4.0 g/day), microscopic haematuria, moderate hypertension, macrothrombocytopenia (giant platelets, platelet number 30 x 10(9)/l) and a familial sensorineural hearing loss (the father and the [ncbi.nlm.nih.gov]

  Hereditary nephritis is a genetically heterogeneous disorder characterized by nephritic syndrome (ie, hematuria, proteinuria, hypertension, eventual renal insufficiency) often with sensorineural deafness and, less commonly, ophthalmologic symptoms. [merckmanuals.com]

• Blurred Vision

  A macular hole causes blurred or distorted central vision. The goals of treatment include monitoring and controlling the disease and treating the symptoms. [nlm.nih.gov]

  Recurrent corneal erosions can cause discomfort or severe eye pain, an abnormal sensitivity to light (photophobia), blurred vision, and the sensation of a foreign body (such as dirt or an eyelash) in the eye. [rarediseases.org]

• Hearing Impairment

  Hearing impairment Sensorineural deafness is a characteristic feature observed frequently, but not universally, in patients with Alport syndrome. Some families with Alport syndrome have severe nephropathy but normal hearing. [emedicine.medscape.com]

  At the initial stages of development the following is observed: decreased vision; hearing impairment (in some cases down to deafness in one ear) blood in the urine. [brulanta.com]

  A family history of end-stage renal disease with hearing impairment is suggestive of Alport syndrome, but other conditions can cause this combination of abnormalities. Most can be distinguished by clinical features. [en.wikipedia.org]

  Clinically distinguish two options: 1) hereditary nephritis with hearing loss (Alport syndrome); 2) hereditary nephritis without hearing impairment. [en.medicine-guidebook.com]

  Hearing impairment in members of families with Alport syndrome is always accompanied by evidence of renal involvement; no convincing evidence that deaf males lacking renal disease can transmit Alport syndrome to their offspring has been reported. [ncbi.nlm.nih.gov]

• Hearing Problem

  Many people with Alport syndrome also have hearing problems and abnormalities with their eyes. [kidney.org]

  Hearing problems, usually an inability to hear sounds in the higher frequencies, are common. Cataracts can also occur, although less often than hearing loss. Abnormalities of the corneas, lenses, or retina sometimes cause blindness. [msdmanuals.com]

• Hematuria

  Other Names for This Condition Congenital hereditary hematuria Hematuria-nephropathy-deafness syndrome Hematuric hereditary nephritis Hemorrhagic familial nephritis Hemorrhagic hereditary nephritis Hereditary familial congenital hemorrhagic nephritis [medlineplus.gov]

  Differential diagnosis The differential diagnoses include hematuria related to urologic diseases and cancer, IgA nephropathy, nephropathy related to MYH9 mutation, and familial benign hematuria. [orpha.net]

  Renal manifestations Hematuria Gross or microscopic hematuria is the most common and earliest manifestation of Alport syndrome. Microscopic hematuria is observed in all males and in 95% of females. [emedicine.medscape.com]

  The proband had experienced microscopic hematuria and occasionally macroscopic hematuria since 3 years of age. [ncbi.nlm.nih.gov]

  Familial hematuria due to type IV collagen mutations: Alport syndrome and thin basement membrane nephropathy. Curr Opin Pediatr. 2004 Apr;16(2):177-81. Review. Kashtan CE. Familial hematurias: what we know and what we don't. [ghr.nlm.nih.gov]

• Renal Insufficiency

  Cases with X-linked inheritance may be clinically categorized as Juvenile form: Renal insufficiency develops between 20 and 30 yr Adult form: Renal insufficiency develops in people > 30 yr Symptoms and Signs Classic X-linked disease in males and autosomal [merckmanuals.com]

  Abstract Hereditary nephritis with deafness, or Alport's syndrome, is a familial disorder characterized by progressive renal insufficiency, sensorineural hearing loss and ocular abnormalities. [ncbi.nlm.nih.gov]

  Monitoring Check 24-hour urinary protein, creatinine, and serum chemistry as follows: Annually in patients without renal insufficiency and in those with mild renal insufficiency Every 6 months in patients with moderate renal insufficiency Every 1-3 months [emedicine.medscape.com]

  Those cases have to be clinically followed closely in case they develop renal insufficiency. Ref: ASN Nephsap July 2011, Pathology [nephronpower.com]

• Macroscopic Hematuria

  The proband had experienced microscopic hematuria and occasionally macroscopic hematuria since 3 years of age. [ncbi.nlm.nih.gov]

  Episodes of gross hematuria may follow sore throats or other infections in children and may be the presenting symptom. Macroscopic hematuria is not common in adults and perhaps a feature of juvenile types of disease. [web.archive.org]

Laboratory workup including haematology, chemistry, immunology and clotting tests was normal with the exception of haematuria. [ncbi.nlm.nih.gov]

Serologic workup was negative for anti-nuclear antibody, hepatitis B surface antigen, hepatitis C antibody and HIV Based on the family history, the pattern of inheritance was consistent with autosomal dominant. [omicsonline.org]

Clinical Testing and Workup The diagnostic approach to confirming a suspected diagnosis of Alport syndrome has been evolving over the past decade. [rarediseases.org]

• Small Kidney

  A number of patients present to nephrologists with end-stage renal failure of unknown cause and many have small kidneys, making renal biopsy inadvisable. [ncbi.nlm.nih.gov]

  When bilateral, kidneys are functional for 5-10 yrs. Constitute 20% of juvenile population on dialysis. What is oligomeganephronia? Small kidneys with exceptionally hypertrophied nephrons. [quizlet.com]

• Bilateral Small Kidneys

  Ultrasound examination revealed bilateral small kidneys. He was severely hypertensive; audiometry and ophthalmic examinations were normal. Thrombocytopenia with giant platelets was observed in peripheral blood smears. [ncbi.nlm.nih.gov]

Up to know, there is no specific and effective treatment for AS. Further studies are necessary to establish novel and effective therapeutic protocols. [pubmed.ncbi.nlm.nih.gov]

Standard Therapies Treatment The treatment of Alport syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. [rarediseases.org]

Without treatment, 90% of males develop kidney failure by 40 years old. Females develop kidney failure less frequently and more slowly. [kidney.org]

Management and treatment The management of AS is only symptomatic, mainly aiming at slowing the progression to ESRD. [orpha.net]

There is no currently known beneficial treatment for these disorders. [ncbi.nlm.nih.gov]

Prognosis The prognosis of AS is poor due to the progression to ESRD (often affecting young adults). However, renal transplantation is usually successful, since the development of anti-type IV collagen antibodies is a rare event. [orpha.net]

ESKD: occurs at an average age of 16-37 years. [ 7 ] Prognosis Prognosis depends on the type of inheritance, the sex of the patient and the type of mutations in type IV collagen genes. [patient.info]

Renal involvement, a common cause of death amongst afflicted subjects, appears to have a better prognosis in the affected members of this family. [ncbi.nlm.nih.gov]

Etiology AS involves a structural defect of type IV collagen, an essential component of the glomerular basal membrane. XLAS is due to mutations in COL4A5 (Xq22.3) gene coding for the alpha 5 chain of type IV collagen. [orpha.net]

Etiology The etiology of hereditary nephrite is still impossible to fully establish. The most likely reason is considered to be a mutation of the gene, which is responsible for the synthesis of proteins in the kidney tissue. [brulanta.com]

It is suggestd that there is a common rather than a divers etiology for ranal disease in children. Longgitudinal follow-up with repeated renal functionl studies and biopsies will be needed to delineate the natural history. [nature.com]

With the development of human genetics, including medical genetics, the hereditary nature of many diseases and syndromes, previously considered illnesses with unknown etiology, became clear. [en.medicine-guidebook.com]

Once microhematuria is provisionally localized to the glomeruli, possible etiologies include a number of chronic glomerulopathies. [ncbi.nlm.nih.gov]

Summary Epidemiology The global prevalence of Alport syndrome (AS) is unknown. The prevalence at birth in Finland is estimated at 1/53,000. In the USA, Alport syndrome reportedly accounts for up to 2% of new cases of pediatric ESRD. [orpha.net]

However, eventually there is the onset of proteinuria associated with the classic and progressive irregular thickening, thinning and splitting of the GBM, which culminates in end-stage kidney disease (ESKD). [ 2 ] Epidemiology Alport's syndrome (AS) is [patient.info]

Original Articles Epidemiology and Outcomes, Anneke Kramer, Kitty J. Jager, Katharina Lange, Frederick Peters, Gerhard-Anton Müller, Reinhard Kramar, James G. Heaf, Patrik Finne, Runolfur Palsson, Anna V. Reisæter, Andries J. [doi.org]

Review Alport Syndrome: A Comprehensive Review on Genetics, Pathophysiology, Histology, Clinical and Therapeutic Perspectives Ana Luisa Pedrosa et al. Curr Med Chem. 2021. [pubmed.ncbi.nlm.nih.gov]

From basic science and pathophysiology to clinical best practices, Brenner & Rector’s The Kidney is your go-to resource for any stage of your career. [books.google.com]

"Alport Syndrome Pathophysiology". News-Medical. https://www.news-medical.net/health/Alport-Syndrome-Pathophysiology.aspx. (accessed December 05, 2022). Harvard Wilson, Damien Jonas. 2019. Alport Syndrome Pathophysiology. [news-medical.net]

1:16 – Blood smear with schistocytes 1:40 – Von Willebrand’s protein synthesis 02:09 – ADAMTS-13 and TTP pathophysiology 02:43 – How to interpret ADAMTS-13 activity testing and advantage of doing ADAMTS-13 activity testing with Machaon Dx 03:48 – Use [machaondiagnostics.com]

Can it be prevented? There is a lot of research going on into how to make the body tolerant of ‘slightly different’ molecules like the Alport molecule. [edren.org]

Prevention There is no prophylaxis of hereditary nephritis. This genetic disease can not be prevented. [brulanta.com]

When mutations prevent the formation of 345 type IV collagen network in the glomerulus, the 112 network, which is formed in fetal development but usually replaced by 345, persists into adult life. [en.wikipedia.org]

Fosinopril Fosinopril is an angiotensin converting enzyme (ACE) inhibitor, prescribed for high blood pressure, heart failure and preventing kidney failure. [medindia.net]

Early detection of the mutation may help to prevent or delay the onset of renal failure, and to detect carrier mothers, who are at a higher risk of renal complications themselves. [news-medical.net]