ESPE Abstracts

Purpose: Clinical problems caused by impaired molecular function of inborn errors of immunity (IEI) genes are not limited to the immunological system but can also affect the endocrine system. An autosomal recessive form of severe congenital neutropenia also known as Kostmann syndrome (KS) is caused by mutations in the gene encoding the mitochondrial protein HAX1. Knowing that most endocrine disorders associated with IEI are hypofunction, a close cooperation between the two specialties hem-oncology and endocrinology is crucial for an early diagnosis, a timely start of supplementation therapy and an appropriate management for favorable long-term outcomes in patients with KS.

Methods: Clinical histories, auxology, pubertal development, laboratory and medical imaging findings of two patients with compound-heterozygous HAX1 deficiency (HAX 1 c.130_131insA, p.W44* (het.); c.430dupG, p.V144Gfs*5 (het.)) were evaluated.

Results: We report of two syrian sisters from non-consanguine parents age 13.5 and 14.5 years with KS, hypothyroidism, short stature, delayed puberty as well as premature ovarian insufficiency. LH/FSH-levels were elevated while Estrogen-, InhibinB-, and AMH-levels were low (hypergonadotropic hypogonadism). The TSH-level and thyroid autoantibodies (TPO-Ab, TG-Ab) were increased while the FT4-level was low. The Ovarian tissue-antibodies were negative and via ultrasound no ovaries were detectable. Chromosome analysis was normal 46,XX. Bone age was delayed.

Conclusions: HAX1 is an ubiquitously expressed protein and therefore mutations in the HAX1 gene can have an effect on numerous body functions such as growth, thyroid and gonadal function besides the immunological functions. Since the introduction of recombinant human granulocyte colony-stimulation factor (G-CSF), most patients with KS enjoy a normal life span and a greatly improved quality of life - but short stature and infertility definitely have a major impact on a patient´s quality of life. So we must be even more vigilant and screen regularly at not too great intervals for dysregulations in the endocrine system to ensure a normal child development. Negative long-term consequences on growth, peak bone mass and reproduction should be avoided at all means. This case report emphasizes the crucial role of a close cooperation between pediatric hem-oncologists and endocrinologists and it highlights the need for an interdisciplinary approach in patients with KS.