880
Cystinosis is a rare, autosomal-reces-
sive inherited metabolic disease char-
acterized by intralysosomal cystine
deposits in all tissues. The cystinosis
gene has been mapped to chromosome
17p13, and mutations have been iden-
tified in CTNS, a gene encoding an in-
tegral lysosomal membrane protein,
cystinosin.
1,2
Growth retardation is
a clinical hallmark in patients with
nephropathic cystinosis
3-6
; in one study
the mean adult height was 136.5 cm in
Long-term treatment with growth hormone in
short children with nephropathic cystinosis
Elke Wühl, MD, Dieter Haffner, MD, G. Offner, MD, Michel Broyer, MD, William van’t Hoff, MD, and
Otto Mehls, MD, for the European Study Group on Growth Hormone Treatment in Children with
Nephropathic Cystinosis
From the Renal Units, the Department of Pediatrics, University Hospital of Heidelberg, Germany, the University
Hospital of Hannover, Germany, Hôpital Necker, Paris, France, and Great Ormond Street Hospital, London, Unit-
ed Kingdom.
Participating centers and MDs for the European Study Group on Growth Hormone Treatment in
Children with Nephropathic Cystinosis in alphabetical order:
G. Champion (Angers, France), J. Gellermann (Berlin, Germany), S. Hulton (Birmingham,
UK), E. Bonzel (Essen, Germany), D.E. Müller-Wiefel (Hamburg, Germany), N. Albers, G.
Offner, (Hannover, Germany), D. Haffner, O. Mehls, E. Wühl (Heidelberg, Germany; Coordina-
tors), C. Holmberg (Helsinki, Finland), W. van’t Hoff, S. Rigden (London, UK), H. P. Weber
(Lüdenscheid, Germany), M. Foulard (Lille, France), P. Cochat (Lyon, France), J. Ardissino,
(Milano, Italy), K. Pistor (Moers, Germany), J.-L. André (Nancy, France), M.C.J.W. de Jong,
E.A.M. Cornelissen (Nijmegen, Netherlands), A. Bensman, D. Deschenes, C. Loirat, M. Broyer,
(Paris, France), M. Wigger, (Rostock, Germany), G. Landthaler (Rouen, France), M.
Fischbach (Strasbourg, France), F. Bouissou (Toulouse, France), H. Nivet (Tours, France) M.
Lilien (Utrecht, Netherlands)
Submitted for publication Apr 26, 2000; revisions received Aug 17, 2000, and Oct 27, 2000;
accepted Nov 30, 2000.
Reprint requests: Otto Mehls, MD, Division of Pediatric Nephrology, University Children’s
Hospital, INF 150, 69120 Heidelberg, Germany.
Copyright © 2001 by Mosby, Inc.
0022-3476/2001/$35.00 + 0 9/21/113263
doi:10.1067/mpd.2001.113263
CRF Chronic renal failure
GFR Glomerular filtration rate
GH Growth hormone
HbA
1c
Glycosylated hemoglobin
oGTT Oral glucose tolerance test
SDS Standard deviation score
Objective: The objective was to assess the efficacy and safety of growth hormone (GH) treatment in severely growth
retarded children with nephropathic cystinosis during conservative treatment and during renal replacement therapy.
Study design: The design was an open-labeled prospective trial with a
run-in period of 1 year.
Results: A total of 74 children with cystinosis (age 3.0 to 18 years) were treated with GH over a mean period of 3.1
years (range 1 to 10 years); 52 patients were receiving conservative treatment (mean age 7.1 years), 7 were receiving
dialysis (12.5 years), and 15 had received a renal transplant (14.8 years). The mean standardized height (SD score)
was –4.0 in the conservative treatment group, –4.4 in the dialysis group, and –4.9 in the renal transplant group. Dur-
ing the first treatment year, height velocity doubled in the conservative treatment group, increased by 80% in the dial-
ysis group, and increased by 45% in renal transplant group. Within 3 years the height SD score increased by +1.6
(P < .001) in prepubertal patients receiving conservative treatment, and percentile parallel growth was maintained
thereafter. These effects of GH were less expressed in peripubertal patients receiving renal replacement therapy.
No major side effects were observed.
Conclusion: Long-term GH treatment is safe and effective in young children with nephropathic cystinosis. GH treat-
ment should be started early in the course of the disease if adequate nutrition and cysteamine treatment do not prevent
growth retardation. (J Pediatr 2001;138:880-7)