Spondyloocular syndrome (OMIM 605822) is an autosomal recessive disorder characterized by skeletal complaints (osteoporosis, platyspondyly, multiple bone fractures), hearing loss and ocular symptoms (cataracts, retinal detachment). XYLT2 gene (OMIM 608125) mutation encoding xylosyltransferase II enzyme which is responsible from the first step of proteoglycan assembly is responsible for the pathogenesis. Phenotypical variability is associated with varying genetic expression. Two siblings diagnosed with spondyloocular syndrome treated with pamidronate therapy will be presented.
First patient was consulted for gait disorder, lumber pain and inability to run at the age of 11. At the age of 1.5, she was operated for bilateral congenital cataracts, had nystagmus. She was diagnosed with retarded growth and development when she was 2,5 years old, retinal detachment at the age of 10. Third degree consanguinity was present. On physical examination her weight was 33.2 kg (25-50p), height was 125.6 cm (<3p). Disproportionate short stature was obvious (Upper/Lower ratio 0.76), pectus excavatum deformity, an increase in the lumbar lordosis and scoliosis, horizantal nystagmus and mild mental retardation were present. 25-OH vitamin D was deficient. Lateral vertebral scan revealed severe osteoporosis, vertebral corpus collapses and platyspondyly apparent in the thoracic segment. Lumbar bone mineral densitometry z-score was -3.6. Spondyloocular syndrome was suspected, XYLT2 gene sequence analysis was performed, a homozygote new mutation on 11. exome (c.2548G>A (p.Asp850Asn)) was recognized, same homozygote mutation was detected in patient's seven year old brother. He was diagnosed with bilateral congenital cataracts, severe mental retardation, global motor and developmental delay, was unable to walk. He weighed 25 kg (50-75p), his height was 108 cm (<3p), proportionate short stature (upper/lower ratio:0.96), kyphosis, and increase in lumbar lordosis were noted. 25-OH vitamin D was deficient. Lateral lumbar X-ray revealed vertebral collapses and platyspondyly apparent in the thoracic and lumbar vertebrae. Lumbar bone mineral densitometry z-score was -2.3. Pamidronate (9 mg/kg/year) and vitamin D replacement therapy were initiated. After the first year of the therapy, bone mineral density z-scores have increased, vertebral corpus heights remained unchanged (BMD L1-L4 z-score were -1.8 and -0.5, respectively).
Spodyloocular syndrome is a rare disorder identified in 2001. Therapy options for the disease are limited and sufficient data on pamidronate therapy are lacking. Previously, three patients diagnosed with Spondyloocular Syndrome wha received pamidronate therapy were reported, although bone mineral density has increased, new vertebral and long bone fractures could not be prevented. More data is required to understand disease course and determine therapy options.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology