Growth, final height and endocrine sequelae in a UK population of patients with Hurler syndrome (MPS1H).
OBJECTIVE
Hurler Syndrome, (MPSIH) is an inborn error of glycosaminoglycan metabolism. Haematopoietic stem cell transplantation (HSCT) has transformed the prognosis for these children. Prior to transplant patients receive chemotherapy or chemo-radiotherapy. Regular screening for the development of endocrine sequelae is therefore essential. We present for the first time data on final adult height and endocrine complications in children with MPSIH post HSCT.


METHODS
Retrospective case note study and a prospective programme of growth and endocrine assessment.


METHODS
22 patients were included, mean age at last assessment 12.2 (Range 6.3-21.6) years. Mean age at HSCT was 1.3 (SD 0.6) years. Conditioning included mostly busulphan and cyclophosphamide, with 5 patients receiving total body irradiation prior to second transplant.


RESULTS
Height SDS decreased over time. Final height (FH) was attained in seven patients with male FH SDS -4.3 (Range -3.8, -5.1) and female FH SDS -3.4 (Range -2.9, -5.6). Eight of 13 patients tested had evidence of high growth hormone (GH) levels, while one had GH deficiency. Adrenal and thyroid function was normal in all. 11 patients were pubertal or post pubertal. Two females had pubertal failure requiring intervention. All male patients had spontaneous, complete puberty; however three patients have reduced testicular volumes. Five out of 13 patients tested had an abnormal oral glucose tolerance test.


CONCLUSIONS
Growth is impaired, primarily related to skeletal dysplasia, but also associated with GH resistance. Pubertal development may be compromised and abnormalities of glucose metabolism are common. We recommend a structured endocrine surveillance programme for these patients.
Royal Manchester Children's Hospital, Manchester, UK. cgardner@nhs.net
Chris J
CJ
Gardner
Nicola
N
Robinson
Tim
T
Meadows
Robert
R
Wynn
Andrew
A
Will
Jean
J
Mercer
Heather J
HJ
Church
Karen
K
Tylee
J Edmond
JE
Wraith
Peter E
PE
Clayton
D000293:Adolescent; D000328:Adult; D001827:Body Height; D002066:Busulfan / Q000494:pharmacology; D002648:Child; D003520:Cyclophosphamide / Q000494:pharmacology; D004703:Endocrine System; D004700:Endocrine System Diseases / Q000150:complications; D005260:Female; D005951:Glucose Tolerance Test; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D008297:Male; D008059:Mucopolysaccharidosis I / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D012189:Retrospective Studies; D019172:Transplantation Conditioning; D006113:United Kingdom
D006025:Glycosaminoglycans; D003520:Cyclophosphamide; D002066:Busulfan
Genet Med. 2003 Jul-Aug;5(4):286-94
12865757
Bone Marrow Transplant. 1995 Jun;15(6):873-7
7581084
Lancet. 2000 Sep 16;356(9234):993-7
11041401
Arch Pathol. 1974 Feb;97(2):96-9
4358599
Haematologica. 2006 Dec;91(12 Suppl):ELT12; author reply ELT13
17194672
Bone Marrow Transplant. 2005 Mar;35 Suppl 1:S77-81
15812537
J Pediatr (Rio J). 2008 Mar-Apr;84(2):136-40
18350228
Bone Marrow Transplant. 2001 Jul;28(1):67-75
11498747
Arch Dis Child. 1997 Feb;76(2):92-9
9068295
Acta Pathol Jpn. 1988 Sep;38(9):1175-90
2853931
Clin Endocrinol (Oxf). 1995 Apr;42(4):333-9
7750186
J Pediatr Orthop. 2004 Jan-Feb;24(1):97-101
14676543
J Bone Joint Surg Br. 1994 Nov;76(6):975-81
7983131
Diabetes Care. 1998 Dec;21(12):2191-2
9839117
Bone Marrow Transplant. 2009 Sep;44(6):339-43
19308039
Bone Marrow Transplant. 2009 Sep;44(5):279-85
19252529
Clin Pediatr (Phila). 2009 Jul;48(6):601-8
19264722
Mol Genet Metab. 2010 Jan;99(1):10-7
19783188
Bone Marrow Transplant. 2009 Apr;43(8):637-42
19011662
Bone Marrow Transplant. 2008 Jun;41(12):1005-11
18278070
N Engl J Med. 2004 May 6;350(19):1960-9
15128896
Bone Marrow Transplant. 2004 May;33(10):1049-56
15048143
Bone Marrow Transplant. 2007 Feb;39(4):207-10
17220904
J Inherit Metab Dis. 2004;27(5):685-6
15669685
Horm Res. 2006;65 Suppl 1:28-34
16508331
Bone Marrow Transplant. 2001 Jul;28(2):201-5
11509939
Bone Marrow Transplant. 2006 Jun;37(12):1109-17
16699534
Pediatr Hematol Oncol. 2004 Jul-Aug;21(5):411-9
15205084
Acta Pathol Jpn. 1976 Jan;26(1):115-32
132078
Bone Marrow Transplant. 2007 Apr;39(8):483-90
17334386