Ultrasonographic hip morphology in mucopolysaccharidosis type I Hurler after hematopoietic stem cell gene therapy

Abstract

Purpose: To assess ultrasonographic features of hip morphology in mucopolysaccharidosis type I Hurler.

Methods: Acetabular bony rim, acetabular cartilaginous roof, alpha and beta angles, echogenicity, and hip coverage were analyzed in eight mucopolysaccharidosis type I Hurler syndrome children before and after hematopoietic stem cell gene therapy.

Results: Sixteen hips at baseline, 10 at +12 months, and 10 at + 24 months after hematopoietic stem cell gene therapy were evaluated. The median age was 22, 35, and 45 months at baseline evaluation, +12, and +24 months, respectively. Acetabular bony rim at baseline was angular in 2/16, rounded in 10/16, notched in 2/16, and flattened in 2/16; at +12 months, angular in 2/10, rounded in 5/10, notched in 3/10; at +24 months, angular in 2/10, rounded in 3/10, irregular in 1/10, and notched in 4/10. Acetabular cartilaginous roof at baseline was normal in 4/16, enlarged in 12/16; at +12 months, enlarged in 10/10 and at +24 months, enlarged in 8/10 and normal in 2/10. Echogenicity of the joint capsule at baseline was normal in 10/16, increased in 6/16; at +12 months, normal in 8/10, increased in 2/10; at +24 months, normal in 6/10, increased in 4/10. The mean femoral head coverage was 60% at baseline (16/16), 62% at +12 months (10/10), and 52% at +24 months (2/10). The mean alpha angle was 60° at baseline (16/16), 64° at +12 months (10/10), and 60° (2/10) at +24 months. The mean beta angle was 67° at baseline (16/16), 65° at +12 months (10/10), and 49° at +24 months (8/10).

Conclusions: Hip morphology of children with mucopolysaccharidosis type I Hurler syndrome before and after hematopoietic stem cell gene therapy can be evaluated by available ultrasound techniques until a median age of 45 months.

Keywords: Hip morphology; gene therapy; hip dysplasia; mucopolysaccharidosis; ultrasonography.

Figure 1.

Ultrasonographic hip image in a 6-month old healthy child. Anatomical landmarks according to the Graf technique.

Figure 2.

Hip morphometry of the same hip of Figure 1. (a) Femoral head coverage according to Morin et al. (d/D ×100). (b) Alpha angle between base line and bony roof line, beta angle between base line and cartilaginous roof line according to Graf.

Figure 3.

Ultrasonographic hip images of all patients at different timepoints and ages with morphological features according to Table 1 terminology. (a) MPSIH001: left hip, baseline, 22 months old, rounded acetabular bony rim and enlarged roof cartilage. (b) MPSIH002: right hip, +24 months, 38 months old, irregular acetabular bony rim, enlarged roof cartilage, and increased capsule echogenicity. (c) MPSIH003: right hip, baseline, 22 months old, flattened acetabular bony rim and enlarged roof cartilage. Dislocated femoral head. (d) MPSIH004: left hip, baseline, 13 months old, notched bony rim and enlarged roof cartilage. (e) MPSIH005: left hip, baseline, 33 months old, rounded acetabular bony rim and increased capsule echogenicity. (f) MPSIH006: right hip, +6 months, 31 months old, angular acetabular bony rim and enlarged roof cartilage. (g) MPSIH007: left hip, +12 months, 33 months old, rounded acetabular bony rim and enlarged roof cartilage. (h) MPSIH008: left hip, +12 months, 35 months old, notched acetabular bony rim, enlarged roof cartilage, and increased capsule echogenicity. MPSIH: mucopolysaccharidosis type I Hurler syndrome.

Figure 4.

(a) Alpha angle trend before and after HSC-GT. (b) Beta angle trend before and after HSC-GT. (c) Head coverage trend before and after HSC-GT. Dotted lines indicate the threshold of normal hips for each parameter. HSC-GT: hematopoietic stem cell-gene therapy.

Figure 5.

Ultrasonographic hip morphology of patient MPSIH006 at different follow-ups after HSC-GT in comparison with X-ray and MRI for bony and cartilaginous head coverage. (a) Right hip, head coverage at baseline and 23 months of life, 65% according to Morin et al. (bony roof limit = central vertical line, cartilaginous medial and lateral femoral head limits = medial and lateral vertical lines, respectively). Ossific nucleus borders with the femoral head (dashed circle). (b) Right hip, head coverage of 62% according to Morin et al. at 12 months post-HSC-GT and at 37 months of age. Enlarged cartilaginous roof (bony roof limit = vertical line, cartilaginous roof limit = vertical dotted line, labrum acetabulare = arrow). Ossific nucleus borders with the femoral head (dashed circle). (c) Right hip, head coverage at 24 months post-HSC-GT and at 49 months of age, with stable bony coverage (bony roof limit = vertical line, ossific nucleus = dashed circle). (d) X-ray of the pelvis at the same timepoint as (c) for comparison (bony roof limit = vertical line). (e) MRI image at the same timepoint of (c) (bony roof limit = vertical line, cartilaginous roof limit = vertical dotted line). (f) Left hip at the same timepoint of (c) (bony roof limit = vertical line, labrum acetabulare = arrow). In (c) and (f), the inferior margin of the ilium in the fossa acetabuli is covered by the large ossific nucleus and thus not visible. HSC-GT: ematopoietic stem cell gene-therapy; MRI: magnetic resonance imaging.