Background: Mutations of the IGFALS gene have been reported since 2004 in 24 patients, but only 5 of these are females. Case Report: We describe a 14.7-year-old female of a consanguineous Moroccan family with growth retardation and normal-onset but slow progression of puberty without manifest pubertal height gain. Results: At age 3.2 years, the patient's height was 85.5 cm (-2.9 SDS) and her weight 9.9 kg (-2.9 SDS) with a head circumference of 44.5 cm (-3.3 SDS). Serum IGF-I and IGFBP-3 concentrations were low with normal basal and stimulated growth hormone (GH) levels. An IGF-I generation test confirmed a lack of response to GH administration. While onset of puberty occurred at a normal age, no significant pubertal growth acceleration was observed despite progression of breast development. Sequencing of the IGFALS gene revealed a novel homozygous frameshift mutation (c.1291delT) with a stop codon (p.W431GfsX10) leading to undetectable serum levels of acid-labile subunit. Conclusion: We report the phenotype of an adolescent girl with primary IGF-I deficiency due to a novel homozygous mutation of the IGFALS gene, who presented with growth delay, normal pubertal onset with slow progression and no pubertal growth acceleration indirectly suggesting a contributing role of the circulating IGF-I pool in the pubertal growth spurt.

BackgroundCurrent knowledge on the exact ligand causing expression of TREM-1 on neutrophils and monocytes is limited. The present study aimed at the role of underlying infection and of the causative pathogen in the expression of TREM-1 in sepsis.MethodsPeripheral venous blood was sampled from 125 patients with sepsis and 88 with severe sepsis/septic shock. The causative pathogen was isolated in 91 patients. Patients were suffering from acute pyelonephritis, community-acquired pneumonia (CAP), intra-abdominal infections (IAIs), primary bacteremia and ventilator-associated pneumonia or hospital-acquired pneumonia (VAP/HAP). Blood monocytes and neutrophils were isolated. Flow cytometry was used to estimate the TREM-1 expression from septic patients.ResultsWithin patients bearing intrabdominal infections, expression of TREM-1 was significantly lower on neutrophils and on monocytes at severe sepsis/shock than at sepsis. That was also the case for severe sepsis/shock developed in the field of VAP/HAP. Among patients who suffered infections by Gram-negative community-acquired pathogens or among patients who suffered polymicrobial infections, expression of TREM-1 on monocytes was significantly lower at the stage of severe sepsis/shock than at the stage of sepsis.ConclusionsDecrease of the expression of TREM-1 on the membrane of monocytes and neutrophils upon transition from sepsis to severe sepsis/septic shock depends on the underlying type of infection and the causative pathogen.

It is exceptional for PPNAD to be an isolated phenomenon as well as being revealed by progressive weight gain in adolescence.