Abstract: SA-PO0637
A Case of Dent Disease Type 2 Characterized by Proximal Muscle Atrophy, Low-Molecular Weight Proteinuria, and HyperCKemia
Session Information
- Monogenic Kidney Diseases: Tubular and Other
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Maekawa, Shohei, Kyoto Daigaku, Kyoto, Kyoto Prefecture, Japan
- Yamamoto, Shinya, Kyoto Daigaku, Kyoto, Kyoto Prefecture, Japan
- Kang, Youngna, Kyoto Daigaku, Kyoto, Kyoto Prefecture, Japan
- Mohri, Yui, Kyoto Daigaku, Kyoto, Kyoto Prefecture, Japan
- Yoshikawa, Takahisa, Kyoto Daigaku, Kyoto, Kyoto Prefecture, Japan
- Nozu, Kandai, Kobe Daigaku, Kobe, Hyogo Prefecture, Japan
- Yanagita, Motoko, Kyoto Daigaku, Kyoto, Kyoto Prefecture, Japan
Introduction
Dent disease is an X-linked renal tubulopathy characterized by low-molecular-weight proteinuria and nephrocalcinosis, which is accompanied by progressive kidney failure. Mutations in CLCN5 and OCRL1 are responsible for Dent disease type 1 (Dent-1) and type 2 (Dent-2), respectively. The causative OCRL gene encodes an inositol polyphosphate 5-phosphatase. Notably, mutations in OCRL1 can also lead to Lowe syndrome, a systemic disorder characterized by ocular, neurological, and renal manifestations. A diverse spectrum of symptoms has been reported between Dent-2 and Lowe syndrome.
Case Description
The patient is a 47-year-old man with a history of proteinuria since childhood. At the age of 40, he underwent a renal biopsy, which revealed the presence of glomerular cysts with no specific abnormalities identified. He was referred to our hospital with progressive proximal muscle weakness and psoas muscle atrophy. He had no intellectual disability, growth retardation, or ocular symptoms. Laboratory investigations revealed chronic kidney disease, low-molecular-weight proteinuria, nephrocalcinosis, and hyperCKemia. A repeat renal biopsy showed glomerular cysts and nonspecific tubular injury, consistent with the previous findings. Given a family history of renal dysfunction and muscle weakness in his elder brothers, genetic testing was performed, revealing a hemizygous missense mutation in exon 9 of the OCRL1 gene (c.821T＞C, p.Ile274Thr). Based on clinical and genetic findings, he was diagnosed with Dent-2.
Discussion
To our knowledge, this is the first reported case of Dent-2 disease presenting with prominent muscle atrophy as a leading clinical feature. Proximal muscle atrophy is uncommon in individuals with mutations in OCRL1. The p.Ile274Thr variant in the OCRL1 gene has been reported in both Dent-2 and Lowe syndrome, highlighting the phenotypic spectrum of OCRL1-related disorders. Although initial signs of hyperCKemia and muscle weakness suggested a primary myopathy or mitochondrial disorder, these conditions were excluded through genetic testing, underscoring the significance of genetic assessments even in middle-aged individuals. Dent-2 should be considered in patients presenting with unexplained renal dysfunction and neuromuscular symptoms, particularly when there is a suspicion of familial involvement.