Use of recombinant growth hormone in the treatment of short stature in a sibling pair with Dent disease

ABSTRACT

Dent disease (DD) is a rare X-linked recessive proximal tubulopathy characterized by low molecular-weight proteinuria, nephrolithiasis, and slowly progressive renal failure. It is caused by mutations in the chloride channel chloride voltage-gated channel 5 (CLCN5) or the oculocerebrorenal syndrome of Lowe gene. We describe two brothers with genetically confirmed DD type 1 due to a pathogenic CLCN5 duplication (c.351_352dupAA). The elder sibling, diagnosed 9 years after presenting with frothy urine, developed progressive growth retardation despite conventional therapy. At 15 years, his height was −3.5 standard deviation (SD) with a normal growth hormone (GH)–insulin-like growth factor-1 (IGF-1) axis. His younger brother, identified on family screening, had severe short stature (−4.1 SD) and documented GH deficiency on clonidine stimulation. After informed consent from parents, both received recombinant GH (rGH, 0.18 mg/kg/week) in addition to standard management for 1 year. They showed significant height gain without any complications of rGH therapy. Serum phosphate and tubular phosphate reabsorption improved, while renal function and calciuria remained stable. To conclude, short stature in DD is multifactorial, and GH deficiency may be one of the contributing factors. Conventional treatment often fails to address the issue of short stature in these patients. Treatment with rGH demonstrated improved growth velocity and suggests potential therapeutic benefits in these patients regardless of GH–IGF-1 axis function.