Endocrine Abstracts

JOINT3425

Introduction: Cohen Syndrome is a rare autosomal recessive disorder caused by mutations in the VPS13B gene. It is characterized by distinct facial features, mitral valve prolapses, and neurological defects, along with endocrine and musculoskeletal manifestations such as joint laxity, scoliosis, knee deformities, short stature, pubertal delay, and growth hormone deficiency. The underlying pathophysiology is thought to involve impaired protein glycosylation, particularly at the Golgi apparatus. Alkaline Phosphatase (ALP), a glycosylated enzyme involved in bone metabolism and turnover, is affected by glycosylation defects. We hypothesized that individuals with Cohen Syndrome may exhibit low ALP levels, which could potentially represent a new form of hypophosphatasia.

Aim: This study aimed to explore the relationship between Cohen Syndrome and low ALP levels, investigating whether this could signify a new subgroup of hypophosphatasia.

Method: A retrospective review was conducted on nine Cohen Syndrome cases diagnosed at our institution. ALP levels were measured for all patients, and radiologic evaluations were performed to assess skeletal abnormalities. The incidence of low ALP in this cohort was compared to the general population rate of approximately 5%.

Results: Among the nine patients with Cohen Syndrome, 44% (4/9) had low ALP levels, significantly higher than the general population rate (P = 0.0006). Radiologic evaluations revealed bone abnormalities in some patients, including fractures. Specifically, 22% of the individuals had fractures, and one patient with a low-trauma fracture and diffuse osteopenia on X-rays. These findings suggest a potential link between low ALP and skeletal manifestations in Cohen Syndrome, pointing to disturbances in bone metabolism that may be indicative of a new form of hypophosphatasia.

Conclusion: This study identifies a novel association between Cohen Syndrome and low alkaline phosphatase levels, suggesting the possibility of a new subgroup of hypophosphatasia. The significantly high rate of low ALP among our cohort warrants further investigation into the role of bone metabolism in Cohen Syndrome. Confirmatory tests (serum pyridoxal 5’-phosphate and urine phosphoethanolamine) for hypophosphatasia are planned, and these findings could inform future therapeutic strategies. This novel subgroup could provide valuable insights into bone health in genetic disorders, potentially guiding targeted treatments.