Short stature with low insulin-like growth factor 1 availability due to pregnancy-associated plasma protein A2 deficiency in a Saudi family.
Amir BabikerKhalid Al NoaimAbdulrahman Al SwaidMajid AlfadhelAsma DeebÁlvaro Martín-RivadaVicente BarriosLuis A Pérez-JuradoAhmed AlfaresIbrahim Al AlwanJesús ArgentePublished in: Clinical genetics (2021)
In 2016 a new syndrome with postnatal short stature and low IGF1 bioavailability caused by biallelic loss-of-function mutations in the gene encoding the metalloproteinase pregnancy-associated plasma protein A2 (PAPP-A2) was described in two families. Here we report two siblings of a third family from Saudi Arabia with postnatal growth retardation and decreased IGF1 availability due to a new homozygous nonsense mutation (p.Glu886* in exon 7) in PAPPA2. The two affected males showed progressively severe short stature starting around 8 years of age, moderate microcephaly, decreased bone mineral density, and high circulating levels of total IGF1, IGFBP3, and the IGF acid-labile subunit (IGFALS), with decreased free IGF1 concentrations. Interestingly, circulating IGF2 and IGFBP5 were not increased. An increase in growth velocity and height was seen in the prepuberal patient in response to rhIGF1. These patients contribute to the confirmation of the clinical picture associated with PAPP-A2 deficiency and that the PAPPA2 gene should be studied in all patients with short stature with this characteristic phenotype. Hence, pediatric endocrinologists should measure circulating PAPP-A2 levels in the study of short stature as very low or undetectable levels of this protein can help to focus the diagnosis and treatment.
Keyphrases
- growth hormone
- binding protein
- saudi arabia
- bone mineral density
- end stage renal disease
- intellectual disability
- postmenopausal women
- chronic kidney disease
- pi k akt
- body composition
- case report
- newly diagnosed
- zika virus
- preterm infants
- copy number
- body mass index
- peritoneal dialysis
- signaling pathway
- early onset
- ejection fraction
- preterm birth
- gene expression
- pregnancy outcomes
- prognostic factors
- replacement therapy
- cell proliferation
- physical activity
- drug induced