Saethre-Chotzen Syndrome Presenting with Incomplete Renal Fanconi Syndrome

The renal Fanconi syndrome is a defect of proximal tubular function causing aminoaciduria and low-molecular-weight proteinuria. Dent's disease and Lowe syndrome are defined X-linked forms of Fanconi syndrome; there is also an autosomal dominant idiopathic form (ADIF), phenotypically similar to Dent's disease though its gene defect is still unknown. To assess whether their respective gene products are ultimately involved in a common reabsorptive pathway for proteins and low-molecular-mass endogenous metabolites, we compared renal Fanconi urinary proteomes and metabonomes with normal (control) urine using mass spectrometry and1H-NMR spectroscopy, respectively. Urine from patients with low-molecular-weight proteinuria secondary to ifosfamide treatment (tubular proteinuria; TP) was also analyzed for comparison. All four of the disorders studied had characteristic proteomic and metabonomic profiles. Uromodulin was the most abundant protein in normal urine, whereas Fanconi urine was dominated by albumin.1H-NMR spectroscopic data showed differences in the metabolic profiles of Fanconi urine vs. normal urine, due mainly to aminoaciduria. There were differences in the urinary metabolite and protein compositions between the three genetic forms of Fanconi syndrome: cluster analysis grouped the Lowe and Dent's urinary proteomes and metabonomes together, whereas ADIF and TP clustered together separately. Our findings demonstrate a distinctive “polypeptide and metabolite fingerprint” that can characterize the renal Fanconi syndrome; they also suggest that more subtle and cause-specific differences may exist between the different forms of Fanconi syndrome that might provide novel insights into the underlying mechanisms and cellular pathways affected.

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Succinylacetone Effects on Renal Tubular Phosphate Metabolism: A Model for Experimental Renal Fanconi Syndrome

Experimental Biology and Medicine ◽

10.3181/00379727-196-43211 ◽

1991 ◽

Vol 196 (4) ◽

pp. 428-431 ◽

Cited By ~ 22

Author(s):

K. S. Roth ◽

B. E. Carter ◽

E. S. Higgins

Keyword(s):

Fanconi Syndrome ◽

Phosphate Metabolism ◽

Renal Fanconi Syndrome ◽

Renal Tubular

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Hypophosphatemia in a Malnourished Child: When Renal Fanconi Syndrome Does Not Stand for Refeeding Syndrome

Journal of Parenteral and Enteral Nutrition ◽

10.1002/jpen.1177 ◽

2018 ◽

Vol 43 (1) ◽

pp. 166-169 ◽

Cited By ~ 1

Author(s):

Joseph Runde ◽

Edgardo Rivera‐Rivera ◽

Cecelia Pompeii‐Wolfe ◽

Christopher Clardy ◽

Timothy Sentongo

Keyword(s):

Fanconi Syndrome ◽

Malnourished Child ◽

Refeeding Syndrome ◽

Renal Fanconi Syndrome

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Approach to the patient with renal Fanconi syndrome, glycosuria, or aminoaciduria

10.1093/med/9780199592548.003.0041_update_001 ◽

2018 ◽

Author(s):

Detlef Bockenhauer ◽

Robert Kleta

Keyword(s):

Fanconi Syndrome ◽

Tubular Dysfunction ◽

Renal Fanconi Syndrome ◽

Renal Glycosuria ◽

Proximal Tubular Dysfunction ◽

Wide Range ◽

Proximal Tubular ◽

Proximal Tubular Function ◽

Low Molecular Weight Proteins ◽

Filtration Capacity

Up to 80% of filtered salt and water is returned back into the circulation in the proximal tubule. Several solutes, such as phosphate, glucose, low-molecular weight proteins, and amino acids are exclusively reabsorbed in this segment, so their appearance in urine is a sign of proximal tubular dysfunction. An entire orchestra of specialized apical and basolateral transporters, as well as paracellular molecules, mediate this reabsorption. Defects in proximal tubular function can be isolated (e.g. isolated renal glycosuria, aminoacidurias, or hypophosphataemic rickets) or generalized. In the latter case it is called the Fanconi–Debre–de Toni syndrome, based on the initial clinical descriptions. However, in clinical practice it is usually referred to as just the ‘renal Fanconi syndrome’. Severity of proximal tubular dysfunction can vary, and may coexist with some degree of loss of glomerular filtration capacity. Causes include a wide range of insults to proximal tubular cells, including a number of genetic conditions, drugs and poisons.

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Primary Sjӧgren's syndrome with renal Fanconi syndrome: Good responses to treatment with glucocorticoids

Seminars in Arthritis and Rheumatism ◽

10.1016/j.semarthrit.2020.03.017 ◽

2020 ◽

Vol 50 (6) ◽

pp. 1326-1332

Author(s):

Xiaoxiao Shi ◽

Zhixin Chen ◽

Jing Wang ◽

Yubing Wen ◽

Linfeng Zou ◽

...

Keyword(s):

Fanconi Syndrome ◽

Renal Fanconi Syndrome ◽

Primary Sjӧgren’S Syndrome

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A hybrid treatment modality of a subtrochanteric femoral fracture in a patient with osteoporosis due to a renal Fanconi syndrome: a case report

Journal of Surgical Case Reports ◽

10.1093/jscr/rjaa130 ◽

2020 ◽

Vol 2020 (8) ◽

Author(s):

Stefan F Lange ◽

Tim K J Schrooten ◽

Ralph J de Wit ◽

Reinier de Groot

Keyword(s):

Femoral Fracture ◽

Fanconi Syndrome ◽

Treatment Method ◽

Contralateral Side ◽

Fracture Probability ◽

Renal Fanconi Syndrome ◽

Screw Osteosynthesis ◽

Hybrid Treatment ◽

Polymer Implant ◽

Subtrochanteric Femoral Fracture

Abstract A 24-year-old male with an idiopathic renal Fanconi syndrome presented to our ER after a low-energetic fall. Conventional imaging revealed a right subtrochanteric femoral fracture, severely decreased bone quality and cannulated collum femoris screws on the contralateral side. Regular plate-screw osteosynthesis or cephalomedullary implantation was deemed insufficient, due to a high iatrogenic and periprosthetic fracture probability. The decision was made to perform a plate-screw osteosynthesis combined with an intramedullary polymer bone enhancement (IlluminOss), to minimize this risk. No complications occurred perioperatively. The patient was able to walk independently two months postoperatively. This case shows that use of polymer implant as an enhancement of osteosynthesis in repair of fractures in the Fanconi syndrome is a safe and possible useful treatment method.

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Oral carnitine therapy in children with cystinosis and renal Fanconi syndrome.

Journal of Clinical Investigation ◽

10.1172/jci113353 ◽

1988 ◽

Vol 81 (2) ◽

pp. 549-560 ◽

Cited By ~ 28

Author(s):

W A Gahl ◽

I Bernardini ◽

M Dalakas ◽

W B Rizzo ◽

G S Harper ◽

...

Keyword(s):

Fanconi Syndrome ◽

Renal Fanconi Syndrome

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Urinary Megalin Deficiency Implicates Abnormal Tubular Endocytic Function in Fanconi Syndrome

Journal of the American Society of Nephrology ◽

10.1681/asn.v131125 ◽

2002 ◽

Vol 13 (1) ◽

pp. 125-133

Author(s):

Anthony G. W. Norden ◽

Marta Lapsley ◽

Takashi Igarashi ◽

Catherine L. Kelleher ◽

Philip J. Lee ◽

...

Keyword(s):

Fanconi Syndrome ◽

Autosomal Dominant ◽

Apical Cell ◽

Sodium Dodecyl ◽

Tubular Proteinuria ◽

Renal Fanconi Syndrome ◽

Dent’S Disease ◽

Mean Values ◽

Dent's Disease ◽

Idiopathic Fanconi Syndrome

ABSTRACT. Normal reabsorption of glomerular filtrate proteins probably requires recycling of the endocytic receptors megalin (gp330) and cubilin. Both receptors are located on the luminal surface of the renal proximal tubule epithelium. Whether abnormal amounts of receptor are present in the urine of patients with Dent’s disease, Lowe’s syndrome, or autosomal dominant idiopathic Fanconi syndrome was explored. They are all forms of the renal Fanconi syndrome and are associated with tubular proteinuria. Urine samples of equal creatinine contents were dialyzed, lyophilized, and subjected to electrophoresis on nonreducing sodium dodecyl sulfate-5% polyacrylamide gels. Proteins were blotted and probed with anti-megalin IgG, anti-cubilin IgG, or receptor-associated protein. Megalin and cubilin levels detected by immunochemiluminescence were measured as integrated pixels and expressed as percentages of the normal mean values. A striking deficiency of urinary megalin, compared with normal individuals (n = 42), was observed for eight of nine families with Dent’s disease (n = 10) and for the two families with Lowe’s syndrome (n = 3). The family with autosomal dominant idiopathic Fanconi syndrome (n = 2) exhibited megalin levels within the normal range. The measured levels of cubilin were normal for all patients. These results are consistent with defective recycling of megalin to the apical cell surface of the proximal tubules and thus decreased loss into urine in Dent’s disease and Lowe’s syndrome. This defect would interfere with the normal endocytic function of megalin, result in losses of potential ligands into the urine, and produce tubular proteinuria.

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