A Case of Spondylodysplastic Ehlers-Danlos Syndrome With Comorbid Hypophosphatasia

Background/objective: Spondylodysplastic Ehlers-Danlos syndrome (spEDS) is a rare subtype of the heritable connective tissue disorder characterized in the 2017 Ehlers-Danlos syndrome (EDS) nosology. Three biallelic mutations, , , and , confirm the diagnosis of spEDS. Hypophosphatasia (HPP) is a heritable disorder caused by a genetic sequence variation in the gene affecting bone mineralization. Common symptoms in the adult form of HPP are joint pain, muscle hypotonia, and metatarsal fractures. Here we present a case of spEDS and HPP in a patient.

Case Report: A 38-year-old woman was evaluated for chronic diffuse joint pain and a low alkaline phosphatase level of 27 U/L (reference, 31-125 U/L). In addition, she presented with a history of hypermobility, limb bowing, and hyperextensible skin, prompting genetic testing for EDS and HPP. The results returned significant for a synonymous sequence variant at c.441G>A in the gene indicative of spEDS. HPP was clinically diagnosed by a repeat low alkaline phosphatase level of 23 U/L and high vitamin B6 level of 24.4 ng/mL (reference, 2.1-21.7 ng/mL), despite the absence of the gene sequence variation on genetic testing.

Discussion: Remarkable personal and family history of this patient suggest that co-occurrence of EDS and HPP is not merely coincidental. Given the overlapping features of muscle hypotonia and joint pain between the 2 heritable disorders, a possible relationship between the 2 may have been previously overlooked.

Conclusion: Further investigation in the relationship and management of the 2 heritable diseases is warranted as enzyme replacement therapy, asfotase alfa, approved for infantile and juvenile onset of HPP may improve the symptoms shared with EDS.