Cockayne syndrome with recurrent acute tubulointerstitial nephritis

Abstract

A 12-year-old girl, who had been diagnosed as having Cockayne syndrome (CS), was admitted for emaciation and dehydration. On admission the patient had mild chronic renal failure (glomerular filtration rate: GFR 50 mL/min) and hyperuricemia. After rehydration, allopurinol was commenced for her hyperuricemia. Then, her renal function rapidly deteriorated (GFR 20 mL/min) with enhancement of proximal tubular dysfunction and hypertension. A renal biopsy showed that the patient had acute tubulointerstitial nephritis (ATIN). Based on this diagnosis, allopurinol was stopped and prednisolone was started (2 mg/kg per day), following which the renal tubular function improved. However, the proteinuria intensified to become nephrotic syndrome. After 1 month the patient developed a gastric ulcer. Famotidine was commenced but GFR deteriorated and renal proximal tubular dysfunction re-occurred. The renal pathology was evaluated by referring to the previous reports of renal pathology in CS. It is suggested that rapid deterioration of the renal function in CS patients might be the result of ATIN. In addition, the present nephrotic syndrome seemed to be accompanied by ATIN, as in other reports.

A novel DNA repair disorder with thrombocytopenia, nephrosis and features overlapping Cockayne syndrome

“…A literature search did not reveal any other reports of CS in association with thrombocytopenia. Two other children with a diagnosis of CS, who have died as a result of nephrotic syndrome, have previously been described [Reiss et al, 1996;Funaki et al, 2006]. In the report by Reiss et al [1996], there was a marginal hypersensitivity to sister chromatid exchanges induced by UVC but not to those induced by UVB.…”

“…While approximately 10% of patients with CS develop renal pathology, this rarely leads to serious complications [Hirooka et al, 1988;Sato et al, 1988;Reiss et al, 1996]. Renal changes may vary significantly between affected individuals but typically include tubulointerstitial inflammation, interstitial fibrosis and tubular atrophy [Hirooka et al, 1988;Funaki et al, 2006]-all consistent with nonspecific end-stage renal disease. A small simplified glomerular structure with wrinkling of the basement membrane appears to be specific to Cockayne Syndrome [Funaki et al, 2006].…”

“…Renal changes may vary significantly between affected individuals but typically include tubulointerstitial inflammation, interstitial fibrosis and tubular atrophy [Hirooka et al, 1988;Funaki et al, 2006]-all consistent with nonspecific end-stage renal disease. A small simplified glomerular structure with wrinkling of the basement membrane appears to be specific to Cockayne Syndrome [Funaki et al, 2006]. Thrombocytopenia has not, to our knowledge, been reported previously in association with CS.…”

Elevated Urinary Levels of 8-Hydroxy-2′-deoxyguanosine in a Japanese Child of Xeroderma Pigmentosum/Cockayne Syndrome Complex with Infantile Onset of Nephrotic Syndrome

“…The effect of the R616G was also predicted to be deleterious by in silico algorithms; Polyphen2 (http://genetics.bwh.har vard.edu/pph2), SIFT (http://sift.bii.a-star.edu.sg/), and Mutation Taster (http://www.mutationtaster.org/). Nephrotic syndrome has been previously reported in several children with CS (Ohno and Hirooka 1966: Higginbottom et al 1979: Hirooka et al 1988: Sato et al 1988: Reiss et al 1996: Funaki et al 2006). All these children share the same pathological features of biopsied renal tissues, including thickening of the glomerular basement membrane and mesangium, collapse of capillary loops, hyalinization of glomeruli, tubular atrophy, and interstitial fibrosis.…”

“…This suggests that the prognosis of CS depends on the management of renal failure throughout the long-term clinical course. There are some reports describing CS patients with complications such as renal failure, but their molecular backgrounds have not been described in their case studies (Ohno and Hirooka 1966: Higginbottom et al 1979: Hirooka et al 1988: Sato et al 1988: Reiss et al 1996: Funaki et al 2006.…”