Growth patterns and the use of growth hormone in the mucopolysaccharidoses

Abstract

Short stature is characteristic of patients with mucopolysaccharidosis (MPS) diseases. For children with skeletal dysplasias, such as MPS, it is important to know the natural history of growth. An understanding of the natural growth pattern in each MPS disease provides a measurement to which treatments can be compared, as well as data which can help families and providers make individualized decisions about growth promoting treatments. Multiple advancements have been made in the treatment of MPS with both hematopoietic cell transplantation (HCT) and enzyme replacement therapy (ERT). The long term benefit of these treatments on growth is unknown. This article will review the published data on growth in children with MPS, and describe preliminary data on the use of human growth hormone (hGH) in children with MPS.

Keywords: Growth; MPS; endocrine disease; growth hormone; mucopolysaccharidoses.

Fig. 1

(A) A longitudinal histological section of a decalcified epiphyseal growth plate from a control cat with clearly defined growth zones. In the calcified cartilage zone, osteoblasts line the trabecule (arrows). RZ (resting zone), PZ (proliferative zone), HZ (hypertrophic zone), CC (calcified cartilage). Magnification × 150. (B) A midline longitudinal histological section of a decalcified epiphyseal growth plate from a cat with MPS VI. Note that the different zones are distinguishable, but there are clear differences in the organization and structure of tissue and cells compared with the control cat of A. There is a disruption of the proliferate zone, and a loss of columnation of the hypertrophic zone. Magnification × 150. (C) A higher magnification of normal chondrocytes in the resting zone of the control cat of A. Magnification × 400. (D) A higher magnification of the resting zone of an MPS VI-affected animal. Note the larger, swollen, vacuolated cells with clumped cytoplasm that is separated from the plasma membrane, and indistinct nucleus. Magnification × 400. (E) A higher magnification of the proliferative zone of a control animal. Note the well-defined columns with an even height and number of cells. Individual cells have some normal degree of flatness with internal spaces filled with cytoplasm, and a clearly distinguishable nucleus. Magnification (F) A higher magnification of the proliferative zone of an MPS VI cat. The columns are poorly organized, with fewer cells per column. Note the flattened cells showing a condensed cytoplasm separated from the plasma membrane, and an indistinct nucleus. Magnification × 400. (From Abreu et al. Growth Plate Pathology in Feline Mucopolysaccharidosis VI. Calcif Tissue Int. 57 (1995), 185–190, with permission.).

Fig. 2

Growth patterns of boys (a) and girls (b) from time of hematopoietic stem cell transplantation (HSCT) to time of last follow-up visit superimposed on standard Centers for Disease Control and Prevention (CDC) percentiles for height by age. (From Polgreen et al. Growth and endocrine function in patients with Hurler syndrome after hematopoietic stem cell transplantation, BMT 41 (2008), 1005–1011, with permission).

Fig. 3

Linear growth chart showing gradual falling off of height (A) and sitting height and subischial leg length: note the relative position of the latter (B). (From Vellodi et al. Bone marrow transplantation for mucopolysaccharidosis type I: experience of two British centres. Arch Dis Child 76 (1997), 92–99, with permission.).

Fig. 4

Linear growth in study patients. (From Young and Harper. Mild form of Hunter’s syndrome: clinical delineation based on 31 cases. Arch Dis Child 57 (1982), 828–836, with permission.)

Fig. 5

Growth velocity before and after 1 year of treatment with GH for eight children with MPS IH. Each child is represented by a pair of connected points: the left point is growth velocity before treatment with GH and the right point is growth velocity1 year later. The size of the point is proportional to the dose of GH (ranging from 0.26 to 0.45 mg/kg/week). The eight children are shown, within their age group (6–7 years, 8–9 years, 10 years and older) against reference levels for growth velocity mean (white horizontal lines) and 2 s.d. (gray rectangles) calculated from 48 children with MPS IH after HCT not treated with GH. GH=growth hormone; MPS IH=mucopolysaccharidosis type IH. (From Polgreen et al. Short-term growth hormone treatment in children with Hurler syndrome after hematopoietic cell transplantation. BMT. 2009; Mar 2: Epub ahead of print, with permission.)