Background:
ACP5 deficiency is known to cause spondyloenchondrodysplasia (SPENCD), which is characterized by various autoimmune and neurological symptoms in addition to short stature.
Methods:
Two siblings from a consanguineous Turkish family, a girl aged 13 years (P1) and a boy aged 8 years (P2), presented to their endocrinologist with progressive growth failure and severe short stature (-5 SDS). They had no comorbid conditions and, on physical examination, there were no signs of an overt skeletal dysplasia with normal appearance of extremities. Other than a low baseline IGF-1, extensive laboratory workup, including growth hormone stimulation and IGF-1 generation tests, was normal. Exome sequencing was performed.
Results:
Exome sequencing identified the presence of a homozygous frameshift mutation (p.Ser258Trpfs*39) in ACP5 in both siblings, which was confirmed by Sanger sequencing. This specific mutation has previously been described in patients with SPENCD. Additional workup in the two siblings showed distinct features of skeletal dysplasia on X-rays consistent with SPENCD, but none of the common autoimmune or neurological abnormalities associated with this condition.
Conclusion:
Severe short stature can be the only presenting sign of ACP5 deficiency and the latter could therefore be considered as a rare cause in the differential diagnosis of severe, proportionate growth failure.