A 9-year-old boy experienced an unusual transition from a kidney that appeared normal to one with the classical characteristics of Alport syndrome, according to a case study.
The article about him, “A unique evolution of the kidney phenotype in a patient with autosomal recessive Alport syndrome,” appeared in the journal Human Pathology.
Alport syndrome is a genetic disorder caused by mutations affecting genes that encode collagen IV, the main component of the kidney’s filtering system, known as the glomerular basement membrane (GBM). In the presence of faulty collagen IV, the kidneys are unable to filter properly due to changes in the membrane’s structure.
Researchers at Vanderbilt University Medical Center said the boy’s initial kidney tissue analysis showed a normal filtering membrane structure.
“These findings have important implications for the interpretation of normal thickness of GBMs in young patients with a family history suggestive of [Alport syndrome],” the researchers wrote.
The boy had had blood and proteins in his urine since he was 3. An initial examination did not find significant physical or blood test abnormalities.
He had a family history of chronic kidney disease, however: His maternal grandfather had had the disorder.
To evaluate his kidney condition, doctors did a renal biopsy. It revealed signs that pointed toward another type of kidney disorder, Berger’s disease. Doctors also found signs of fibrosis and antibodies. But the boy’s filtering membrane was of normal thickness and there were no structural problems with it.
Based on these findings, the team diagnosed him with Berger’s disease. They began treating him with prednisone, fish oil, and Prinivil (lisinopril). The regimen was unable to keep his kidney function under control, however.
Four years after his kidney symptoms began, he lost the high range of his hearing. This prompted doctors to give him a genetic test for Alport syndrome. It revealed a mutation of the COL4A3 gene.
Doctors then re-analyzed his initial kidney biopsy tissue, focusing on the collagen IV-alpha3 chain. It showed that most of the tissue lacked this protein but that the filtering membrane had it. Along with the previous data, the new findings prompted the team to conclude that he had autosomal recessive Alport syndrome (ARAS) and Berger’s disease.
They began treating him with CellCept (mycophenolate mofetil), prednisone, Prinivil, Norvasc (amlodipine), Lipitor (atorvastatin), and Cozaar (losartan). The regimen offered him only limited benefits.
When he was 14, doctors performed a second kidney biopsy. It showed more tissue fibrosis but no major antibody deposits. And this time doctors found the filtering membrance to be thinner and to have mild structural changes. At that point, the team came up with a final diagnosis of autosomal recessive Alport syndrome.
Because his condition continued to worsen, the boy finally received a kidney transplant from his mother, who showed no signs of the disease. But after the transplant, his blood and urine analysis continued to suggest kidney impairment. When doctors did a biopsy of the transplanted kidney, they discovered that the filtering membrane was thin, suggesting that the mother was an asymptomatic ARAS carrier.
“Thinning of the GBM is the earliest ultrastructural manifestation seen in [Alport syndrome], and is thought to be present from the earliest onset, even in utero or in infancy,” the researchers wrote.
What made this case usual was that it showed a different progression of the disease than they had seen before, they wrote.