Distal renal tubular acidosis in a boy with Proteus syndrome
Authors: Prasad Narayan, Rangaswamy Dharshan, Gupta Amit, Sharma Raj Kumar, Bhadauria Dharmender, Kaul Anupama
Journal: Kidney International (2013)

A 15-year-old boy born of a non-consanguineous marriage presented for evaluation of intermittent gross hematuria persistent since the past 4 months. He had progressive and asymmetrical overgrowth of lower limbs (right 100.5cm> left 96cm), with megadactyly (Figure 1, black arrow) and dilated tortuous veins on feet, increased carrying angle at elbow, and normal fingers of upper limb since birth. He had periumbilical lipoma confirmed with fine-needle aspiration cytology (Figure 1, white arrow with inset), left undescended testis, sparse pubic hair, and pigmented nevi compatible with the diagnosis of Proteus syndrome (PS). Biochemical investigations showed the following results: serum creatinine, 0.8mg/dl; calcium, 8.6mg/dl; potassium, 3.5mmol/l; uric acid, 5.4mg/dl; and normal intact parathyroid hormone and 25(OH) vitamin D levels. His urinary calcium, urate, and oxalate levels were normal. His urinary citrate level was toward the lower limit of normal. His 24-h urine protein was 664mg, and 40–50 red blood cells (RBCs)/high power field with no RBC cast on urine microscopy were detected. His baseline urine pH was 7.15, serum HCO3 was 20.1mmol/l, and serum pH was 7.31. Ammonium chloride loading test revealed a urine pH of 5.97, with serum HCO3 being 15.8mmol/l at 3h, consistent with distal renal tubular acidosis (dRTA). Urine anion gap was 26mmol/l. Non-contrast computed tomography scan (Figure 2a) showed medullary calcific density consistent with nephrocalcinosis in the right kidney, and contrast study (Figure 2b) in early venous phase revealed bilateral dilated and tortuous renal veins with possible collateral formation (white arrow) and calcifications (black arrow).Figure 2Computerized tomography (axial section) of abdomen. Non-contrast computed tomography (CT) study (a) shows multiple calcifications (black arrow), and contrast study (b) in late arterial and early venous phase shows dilated and torturous renal vein with possible collateral formation (white arrow) and calcifications (black arrow).View Large Image Figure ViewerDownload (PPT) PS is a rare sporadic disorder of asymmetric overgrowth of body parts due to somatic mosaicism involving the AKT1 gene on 14q32.33, which has a key role in regulating cell survival, insulin signaling, angiogenesis, and tumor formation. It is characterized by vascular malformations of the capillary, venous, and lymphatic systems, as well as cerebriform connective tissue nevi, epidermal nevi, and dysregulated adipose tissue (lipoma). Less common features include cystic lung disease, ovarian/parotid adenomas, and craniofacial and genito-urinary abnormalities. Genito-urinary abnormalities include undescended testis, renal asymmetry, renal failure, ureteric asymmetry, renal cysts, nephrogenic diabetes, hematuria, hydronephrosis, proteinuria, and hydroureter. The mechanism underlying dRTA in this patient is unknown, and further investigation of biochemical pathways in this area may confirm the association of PS and dRTA.