Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Sep;42(5):1019-1029.
doi: 10.1002/jimd.12134. Epub 2019 Aug 5.

Management of bone disease in cystinosis: Statement from an international conference

Katharina Hohenfellner  1 , Frank Rauch  2 , Gema Ariceta  3 , Atif Awan  4 , Justine Bacchetta  5 , Carsten Bergmann  6 , Susanne Bechtold  7 , Noelle Cassidy  8 , Geroges Deschenes  9 , Ewa Elenberg  10 , William A Gahl  11 , Oliver Greil  12 , Erik Harms  13 , Nadine Herzig  14 , Bernd Hoppe  15 , Christian Koeppl  16 , Malcolm A Lewis  4 , Elena Levtchenko  17 , Galina Nesterova  18 , Fernando Santos  19 , Karl P Schlingmann  20 , Aude Servais  21 , Neveen A Soliman  22 , Guenther Steidle  16 , Clodagh Sweeney  4 , Ulrike Treikauskas  23 , Rezan Topaloglu  24 , Alexey Tsygin  25 , Koenraad Veys  17 , Rodo V Vigier  26 , Jozef Zustin  27 , Dieter Haffner  28
Affiliations

Management of bone disease in cystinosis: Statement from an international conference

Katharina Hohenfellner et al. J Inherit Metab Dis. 2019 Sep.

Abstract

Cystinosis is an autosomal recessive storage disease due to impaired transport of cystine out of lysosomes. Since the accumulation of intracellular cystine affects all organs and tissues, the management of cystinosis requires a specialized multidisciplinary team consisting of pediatricians, nephrologists, nutritionists, ophthalmologists, endocrinologists, neurologists' geneticists, and orthopedic surgeons. Treatment with cysteamine can delay or prevent most clinical manifestations of cystinosis, except the renal Fanconi syndrome. Virtually all individuals with classical, nephropathic cystinosis suffer from cystinosis metabolic bone disease (CMBD), related to the renal Fanconi syndrome in infancy and progressive chronic kidney disease (CKD) later in life. Manifestations of CMBD include hypophosphatemic rickets in infancy, and renal osteodystrophy associated with CKD resulting in bone deformities, osteomalacia, osteoporosis, fractures, and short stature. Assessment of CMBD involves monitoring growth, leg deformities, blood levels of phosphate, electrolytes, bicarbonate, calcium, and alkaline phosphatase, periodically obtaining bone radiographs, determining levels of critical hormones and vitamins, such as thyroid hormone, parathyroid hormone, 25(OH) vitamin D, and testosterone in males, and surveillance for nonrenal complications of cystinosis such as myopathy. Treatment includes replacement of urinary losses, cystine depletion with oral cysteamine, vitamin D, hormone replacement, physical therapy, and corrective orthopedic surgery. The recommendations in this article came from an expert meeting on CMBD that took place in Salzburg, Austria, in December 2016.

Keywords: CKD-MBD; Fanconi syndrome; chronic kidney disease; cystinosis; cystinosis metabolic bone disease; hypophosphatemic rickets; transplantation.

PubMed Disclaimer

Conflict of interest statement

Atif Awan, Justine Bacchetta, Frank Rauch, Erik Harms, Bernd Hoppe, Nadine Herzig, Bernd Hoppe, Ewa Elenberg, William A. Gahl, Christian Koeppl, Elena Levtchenko, Malcolm Lewis, Galina Nesterova, Fernando Santos, Karl P. Schlingmann, Aude Servais, Neveen A. Soliman, Guentehr Steidle, Rezan Topaloglu, Ulrike Treikauskas, Alexey Tsygin, Koenraad Veys, Josef Zustin, Rodo v. Vigier have no conflict of interest. Gema Ariceta received speaker honorarium from Chiesi, Orphan and Horizon and consulting fee from Chiesi. Susanne Bechtold received speaker honorarium from Sandoz and consulting fee from Alexion. Carsten Bergmann received speaker honorarium from Alexion. George Deschennes received consulting honorarium from Chiesi. Dieter Haffner received speaker honorarium from Horizon, Chiesi and Orphan. Katharina Hohenfellner received speaker fee from Orphan and consulting honorarium from Leadiant. This article does not contain any studies with human or animal subjects performed by the any of the authors.

Figures

Figure 1
Figure 1
Distal myopathy of cystinosis, with atrophy of the thenar and hypothenar eminences
Figure 2
Figure 2
Active rachitic bone disease on X‐ray of both legs. Note reduced bone density, widening of the metaphyses, and fraying of the epiphyses
Figure 3
Figure 3
Muscular atrophy and bone deformation, that is, genu valgum
Figure 4
Figure 4
Current understanding of the abnormalities leading to cystinosis metabolic bone disease (CMBD). Virtually all individuals with classical, nephropathic cystinosis suffer from CMBD, related to the renal Fanconi syndrome in infancy and progressive chronic kidney disease (CKD) later in life inducing CKD‐associated mineral and bone disorders (CKD‐MBD). Malnutrition and copper deficiency, but also hormonal disturbances, myopathy, and transplantation may worsen the clinical picture. The cystinosin defect also induces intrinsic bone defects such as osteoblastic and osteoclastic dysfunction. The impact of cysteamine on bone deserves further studies, but high doses of cysteamine may contribute to CMBD. Taken together, all these mechanisms can lead to bone deformities and pains, osteoporosis, fractures, cortical impairment, and short stature in teenagers and young adults
See this image and copyright information in PMC

References

    1. Gahl WA, Bashan N, Tietze F, Bernardini I, Schulman JD. Lysosomal cystine transport is defective in cystinosis. Science. 1982;217:1263‐1265. - PubMed
    1. Town M, Jean G, Cherqui S, et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat Genet. 1998;18:319‐324. - PubMed
    1. Cherqui S, Courtoy PJ. The renal Fanconi syndrome in cystinosis: pathogenic insights and therapeutic perspectives. Nat Rev Nephrol. 2017;13:115‐131. - PMC - PubMed
    1. Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E. Cystinosis: a review. Orphanet J Rare Dis. 2016;11:47. - PMC - PubMed
    1. Nesterova G, Gahl WA. In: Pagon RA, Adam MP, Ardinger HH, et al., eds. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 2001:1993‐2017.

Publication types