Rare Diseases Symptoms Automatic Extraction

C-type natriuretic peptide (CNP) plasma levels are elevated in subjects with achondroplasia, hypochondroplasia, and thanatophoric dysplasia.

[achondroplasia]

Context: C-type natriuretic peptide (CNP) is a crucial regulator of endochondral bone growth. In a previous report of a child with acromesomelic dysplasia, Maroteaux type (AMDM), due to loss-of-function of the CNP receptor (NPR-B), plasma levels of CNP were elevated. In vitro studies have shown that activation of the MEK/ERK MAP kinase pathway causes functional inhibition of NPR-B. Achondroplasia, hypochondroplasia, and thanatophoric dysplasia are syndromes of short-limbed dwarfism caused by activating mutations of fibroblast growth factor receptor-3, which result in over-activation of the MEK/ERK MAP kinase pathway. Objective: To determine if these syndromes exhibit evidence of CNP resistance as reflected by increases of plasma CNP and its amino terminal propeptide (NTproCNP). Design: This was a prospective, observational study. Subjects: Participants were 63 children and 20 adults with achondroplasia, 6 children with hypochondroplasia, 2 children with thanatophoric dysplasia, and 4 children and 1 adult with AMDM. Results: Plasma levels of CNP and NTproCNP were higher in children with achondroplasia with CNP SD scores (SDS) of 1.0 (0.3-1.4) [median (intraquartile range)] and NTproCNP SDS of 1.4 (0.4-1.8) (p<0.0005). NTproCNP levels correlated with height velocity. Levels were also elevated in adults with achondroplasia, CNP SDS 1.5 (0.7-2.1) and NTproCNP SDS 0.5 (0.1-1.0), p<0.005. In children with hypochondroplasia, CNP SDS were 1.3 (0.7-1.5)(p=0.08) and NTproCNP SDS were 1.9 (1.8-2.3)(p<0.05). In children with AMDM, CNP SDS were 1.6 (1.4-3.3) and NTproCNP SDS were 4.2 (2.7-6.2) (p<0.01). Conclusions: In these skeletal dysplasias, elevated plasma levels of proCNP products suggest the presence of tissue resistance to CNP.

Diseases presenting "which result in over-activation of the mek" symptom

  • achondroplasia

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