Disseminated Mycobacterium Avium Infection in a Child with Complete Interferon-γ Receptor 1 Deficiency due to Compound Heterozygosis of IFNGR1 for a Subpolymorphic Copy Number Variation and a Novel Splice-Site Variant.

Complete interferon-γ receptor 1 deficiency is a monogenic primary immunodeficiency caused by IFNGR1 germline defects, with autosomal dominant or recessive inheritance, which results in invasive mycobacterial diseases with varying degrees of severity. Most of the autosomal recessive IFNGR1 mutations are homozygous loss-of-function single-nucleotide variants, whereas large genomic deletions and compound heterozygosity have been very rarely reported. Herein we describe the clinical presentation, diagnosis, and successful treatment with hematopoietic stem cell transplantation of a child with disseminated Mycobacterium avium infection due to compound heterozygosity for a subpolymorphic copy number variation and a novel splice-site variant.

Congenital hypothyroidism treatment in infants: a comparative study between liquid and tablet formulations of levothyroxine.

AIMS: To compare the effects of liquid and tablet formulations of levothyroxine (L-T4) in 78 newborns with congenital hypothyroidism (CH). METHODS: 39 patients received liquid L-T4 (group A) and 39 patients received tablets (group B). Thyroid-stimulating hormone (TSH) and free thyroxine (fT4) were measured and L-T4 dose recorded at onset of therapy and during the first year of treatment. Developmental quotient (DQ) was assessed by Griffiths' mental development scales at 12 months of age. RESULTS: Gestational age, birth weight, screening TSH, etiology and severity of CH, age at onset of therapy and median initial L-T4 dose were similar in both groups. fT4 concentration normalized before 10 days of treatment in all patients. Normalization of TSH concentration was achieved after 7-10 days of therapy in 87% of group A patients and in 82% of group B patients. Group A patients had significantly lower TSH values compared with those of group B at 7-10 days (p = 0.05) and 6-8 months (p = 0.043) of treatment, despite similar L-T4 dose and fT4 concentration. Mean DQ scores were within normal range in all patients. CONCLUSION: We confirmed the efficacy and safety of both formulations. The TSH inhibition trend when using liquid L-T4 may be linked to a higher absorption in comparison to the tablets.

Idiopathic central precocious puberty associated with 11 mb de novo distal deletion of the chromosome 9 short arm.

We report a girl with a de novo distal deletion of 9p affected by idiopathic central precocious puberty and intellectual disability. Genome-wide array-CGH revealed a terminal deletion of about 11 Mb, allowing to define her karyotype as 46; XX, del(9)(p23-pter). To our knowledge, this is the second reported case of precocious puberty associated with 9p distal deletion. A third case associates precocious puberty with a more proximal 9p deletion del(9)(p12p13,3). In our case, more than 40 genes were encompassed in the deleted region, among which, DMRT1 which is gonad-specific and has a sexually dimorphic expression pattern and ERMP1 which is required in rats for the organization of somatic cells and oocytes into discrete follicular structures. Although we cannot exclude that precocious puberty in our del(9p) patient is a coincidental finding, the report of the other two patients with 9p deletions and precocious puberty indeed suggests a causative relationship.