Tohoku J. Exp. Med., 2023 August, 260(4)

Association of Familial Fanconi Syndrome with a Novel GATM Variant

Hiroki Kudo,¹ Ryota Suzuki,² Atsushi Kondo,² Kandai Nozu,² Yuki Nakamura,³ Hitoshi Mikami,¹ Jun Soma³ and Izaya Nakaya³

¹Department of Pediatrics, Iwate Prefectural Central Hospital, Morioka, Iwate, Japan
²Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
³Department of Nephrology and Rheumatology, Iwate Prefectural Central Hospital, Morioka, Iwate, Japan

Fanconi syndrome is a disorder of the proximal renal tubule. Recently, advanced genetic analysis technology has revealed that several genes cause familial Fanconi syndrome. We identified a family with autosomal dominant Fanconi syndrome and chronic kidney disease with a novel glycine amidinotransferase (GATM) variant. Case 1 was a 57-year-old Japanese woman. Her father and two siblings had Fanconi syndrome or chronic kidney disease. She presented to our hospital at the age of 34 years with recurrent glucosuria. Her height and weight were 151 cm and 46.6 kg, respectively. Laboratory tests showed glucosuria, hypophosphatemia, hypouricemia, and normal renal function. Her serum creatinine level gradually increased over the following next two decades, and she developed end-stage renal disease. Case 2, the daughter of Case 1, was a 26-year-old woman. Her height and weight were 151 cm and 37.5 kg, respectively. Glucosuria was detected at the age of 13 years, which led to a referral to our hospital. Urinalysis showed low-molecular-weight proteinuria. She was diagnosed with Fanconi syndrome. At the age of 26 years, she had glucosuria, low-molecular-weight proteinuria, hypouricemia, and normal renal function. Genetic testing of both cases revealed a novel missense variant in GATM. The heterozygous missense variants in GATM have been reported to cause familial Fanconi syndrome, which manifests early in life and progresses to renal glomerular failure by mid-adulthood. The novel GATM variant detected in our cases was suspected to be associated with the development of Fanconi syndrome. GATM variants should be tested in patients with idiopathic Fanconi syndrome.

Key words —— chronic kidney disease; end-stage renal disease; glucosuria; hypophosphatemia; mitochondrial enzyme glycine amidinotransferase

© 2023 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2023 August, 260(4), 337-340.

Correspondence: Izaya Nakaya, M.D., Ph.D., Department of Nephrology and Rheumatology, Iwate Prefectural Central Hospital, 1-4-1 Ueda, Morioka, Iwate 020-0066, Japan.

e-mail: inakaya@chuo-hp.jp