3-hydroxyproline and Nephritis--Hereditary

To develop an evidence-based algorithm for determining the etiology of bilateral sensorineural hearing loss (SNHL) in a child.. The frequency of different etiologies was previously determined. A systematic review of the literature for articles published between 1940 and January 2003 was performed for studies providing information on the diagnosis of each etiology relevant to their clinical presentation.. Connexin mutation testing is highly sensitive and specific. CT scanning of the temporal bones is frequently valuable in detecting inner ear malformations. Routine laboratory studies are rarely helpful. ECG is particularly valuable when a history of syncope or arrhythmias or a family history of sudden death in a young child is elicited. There is no literature to support routine urinalysis for the diagnosis of Alport syndrome and thyroid studies lack specificity in the absence of physical findings (goiter).. An evidence-based algorithm was developed that included: history, physical and audiological evaluation, and ophthalmological evaluation. Further directed investigations may include genetic testing for the Cx26 mutation, CT scan of the temporal bones, ECG and urinalysis.

Topics: Algorithms; Child; Connexin 26; Connexins; Ear, Inner; Electrocardiography; Evidence-Based Medicine; Hearing Loss, Sensorineural; Humans; Hydroxyproline; Mutation; Nephritis, Hereditary; Temporal Bone; Thyroid Function Tests; Tomography, X-Ray Computed

Because disturbed conformation of connective tissue proteins can be accompanied by increased racemization (i.e., an increased ratio of dextrorotatory (D) to levorotatory (L) amino acid molecules), we studied by high-performance liquid chromatography the renal excretion of the D-form of the basement membrane-specific trans-3-hydroxyproline in patients with Alport syndrome. The D/L ratio was significantly higher in patients with Alport syndrome than in patients with other renal diseases or in healthy control subjects. We therefore suggest that this factor may be a simple noninvasive (screening) test for Alport syndrome.

Topics: Adolescent; Adult; Biomarkers; Child; Child, Preschool; Chromatography, High Pressure Liquid; Female; Humans; Hydroxyproline; Infant; Infant, Newborn; Isomerism; Middle Aged; Nephritis, Hereditary

Alport's syndrome is characterised by morphological and structural changes of the renal basement membranes. As the hydroxyproline content of isolated glomerular basement membranes is reduced in patients with Alport's syndrome, it is possible that the renal excretion of 3-hydroxproline (3-OHP), a key substrate of basement membrane collagen, may be altered in such patients. The urinary excretion of 3-OHP was determined by thin layer chromatography in 20 patients with Alport's syndrome, in healthy control subjects, and in patients with other renal diseases. These included patients with poststreptococcal glomerulonephritis, lower urinary tract infection, severe reflux nephropathy, lithium induced nephropathy, polycystic kidney disease, familiar benign haematuria, and renal graft rejection. Urinary excretion of 3-OHP was significantly higher in patients with Alport's syndrome compared with the patients with other renal diseases and the healthy control subjects. All other renal diseases investigated had 3-OHP values within the normal range. Urinary 3-OHP determination detected patients with Alport's syndrome with a high sensitivity (95.2%) and specificity (97.2%). We therefore suggest using urinary 3-OHP determinations as a simple non-invasive screening test for Alport's syndrome.

Topics: Adolescent; Adult; Age Factors; Child; Child, Preschool; Chromatography, Thin Layer; Female; Humans; Hydroxyproline; Infant; Infant, Newborn; Isomerism; Kidney Diseases; Male; Middle Aged; Nephritis, Hereditary