Background: Subcutaneous calcification is a rare clinical symptom in infancy. Progressive evolution and association with brachydactyly could be indicators of Albright hereditary osteodystrophy (AHO). In clinical practice, AHO is difficult to diagnose because of clinical heterogeneity. Typical features of AHO without any evidence of hormone resistance are termed pseudopseudohypoparathyroidism (PPHP; OMIM 612463).
Case report: Male patient referred to study due to short stature. He was the third of unrelated parents (one miscarriage and a male apparently healthy). The pregnancy was complicated due to fetal growth retardation and oligohydramnios. He was delivered at term (birth weight 2170 g (−2.42 SDS), length 43 cm (−3.83 SDS), head circumference 33 cm (−1.38 SDS)). He had right phrenic nerve palsy, cortico-subcortical atrophy and hypotonia. He also was severely malnourished and needed gastrostomy feeding; although this problem was later overcome He has good psychomotor development. He presented an early onset of disseminated calcinosis cutis at the age of 3 months. On examination, at 54/12 years, he has short stature (height 94.8 cm (−4.12 SDS), weight 12.15 kg (−2.44 SDS), BMI 13.52 kg/m2 (−1.23 SDS), subcutaneous diffuse (abdomen and feet) and intra-articular (right shoulder) calcifications and middle phalanx hypoplasia of the 2nd and 5th fingers on both hands. Repeated endocrine investigations showed normal levels of serum calcium, phosphate, PTH, 25-hydroxy vitamin D, and other hormones, except a persistent low value of IGF1 and deficient answer to two provocative test for GH (peak of GH <7.5 ng/ml). On the genetic study, a heterozygous mutation in exon 7 of the GNAS gene (c.568_571del) (p.Asp190Metfs * 14) (*) was found (the novo mutation).
Comments: PPHP is caused by heterozygous inactivating mutations in Gs alpha coding exons of GNAS. The identification of affected patients can raise awareness about this rare disease and reach their best clinical management and improve quality of life. In our patient, short stature most likely results from a combination of multiple factors that include GH deficiency.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology