Autospmal Alport syndrome

DOI 14 References
  • Oka Masafumi
    Department of Pediatrics, Kobe University Graduate School of Medicine
  • Nozu Kandai
    Department of Pediatrics, Kobe University Graduate School of Medicine
  • Iijima Kazumoto
    Department of Pediatrics, Kobe University Graduate School of Medicine
  • Matsuo Masafumi
    Department of Pediatrics, Kobe University Graduate School of Medicine

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Other Title
  • 常染色体性Ａｌｐｏｒｔ症候群

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Abstract

 Alport syndrome (AS) is a hereditary and progressive glomerular nephritis that is frequently associated with sensorineural hearing loss and less ocular changes. It usually presents in children as haematuria and proteinuria, and progresses to end-stage renal disease (ESRD) increasing with age.<br> AS is caused by abnormal type IV collagen which is composed of three α chains complex (α1-α1-α2 and α3-α4-α5, α5-α5-α6). The α3-α4-α5 component is expressed in the glomerular basement membrane (GBM). The α5-α5-α6 component is expressed in the Bowman's capsule but not in the GBM.<br> AS is genetically heterogeneous and X-linked (XLAS), with both autosomal recessive (ARAS), and autosomal dominant (ADAS) has been clarified.<br> XLAS accounts for approximately 85% of affected AS patients. It is caused by mutations in the COL4A5 gene on the X chromosome. XLAS is reported that 90% of male patients are at risk of developing ESRD before the age of 40, and females typically show milder clinical symptoms, although the probability of developing ESRD before the age of 40 year is 12%.<br> ARAS accounts for about 15% of patients with AS. It is caused by homozygous mutations or compound heterozygous mutations in the COL4A3 or COL4A4 genes.<br> ARAS usually presents most severe clinical findings. In our study, about 70% of ARAS from eight families) 71.4% of patients had reached ESRD until 15 years old. ARAS is suggested by presence of one or more of following criteria: (i) severe early disease in both females and males; (ii) parental consanguinity; (iii) absence of severe renal disease in the parents. Recently heterozygous mutations in COL4A3 or COL4A4 have been detected in 40% of families with thin basement membrane nephropathy (TBMN). Today understanding of the mode of inheritance for TBMN and ARAS is that heterozygotes with TBMN can be considered carriers for ARAS, and the offspring from a couple in which both parents have TBMN can be expected to get ARAS. We underline that when you examine the patient whose father and mother have histories of TBMN, should rule out ARAS.<br> ADAS has been observed in a few families. It is caused by heterozygous mutations in the COL4A3 or COL4A4. Both female and male patients show a high clinical variability with renal phenotypes ranging from isolated haematuria to late onset ESRD. When EM findings show TBMN in young patients, it is not able to distinguish ADAS or TBMN. Immunohistochemical study of renal GBMs shows normal pattern in both ADAS and TBMN. Therefore we need the detailed family histories and to follow up the patients whether decrease renal function or not.<br> In conclusion, we described mainly about the autosomal AS. Recently relations between ARAS and TBMN have revealed, AS may be the more frequent disease. It is not revealed what is the difference between ARAS and ADAS in molecular aspects, they have mutations in the same genes of COL4A3 or COL4A4. We will conduct molecular analysis in AS and reveal the mechanism and clinical findings of AS.

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