Whole-exome sequencing identifies tetratricopeptide repeat domain 7A (TTC7A) mutations for combined immunodeficiency with intestinal atresias.

BACKGROUND: Combined immunodeficiency with multiple intestinal atresias (CID-MIA) is a rare hereditary disease characterized by intestinal obstructions and profound immune defects. OBJECTIVE: We sought to determine the underlying genetic causes of CID-MIA by analyzing the exomic sequences of 5 patients and their healthy direct relatives from 5 unrelated families. METHODS: We performed whole-exome sequencing on 5 patients with CID-MIA and 10 healthy direct family members belonging to 5 unrelated families with CID-MIA. We also performed targeted Sanger sequencing for the candidate gene tetratricopeptide repeat domain 7A (TTC7A) on 3 additional patients with CID-MIA. RESULTS: Through analysis and comparison of the exomic sequence of the subjects from these 5 families, we identified biallelic damaging mutations in the TTC7A gene, for a total of 7 distinct mutations. Targeted TTC7A gene sequencing in 3 additional unrelated patients with CID-MIA revealed biallelic deleterious mutations in 2 of them, as well as an aberrant splice product in the third patient. Staining of normal thymus showed that the TTC7A protein is expressed in thymic epithelial cells, as well as in thymocytes. Moreover, severe lymphoid depletion was observed in the thymus and peripheral lymphoid tissues from 2 patients with CID-MIA. CONCLUSIONS: We identified deleterious mutations of the TTC7A gene in 8 unrelated patients with CID-MIA and demonstrated that the TTC7A protein is expressed in the thymus. Our results strongly suggest that TTC7A gene defects cause CID-MIA.

Thiamine-responsive megaloblastic anemia syndrome: long term follow-up.

Thiamine-responsive megaloblastic anemia is a rare autosomal recessive disorder whose main symptoms are anemia, diabetes mellitus, and sensorineural deafness. We describe a 20-year follow-up of 2 previously reported patients and of 1 patient diagnosed before onset of symptoms and treated with thiamine since the first sign of disease.

A family-based education program for obesity: a three-year study.

BACKGROUND: The epidemic of obesity is increasing in all countries. However, the number of controlled studies focusing on childhood obesity, with a long follow-up is still limited. Even though Behavioral Therapy shows some efficacy, it requires a prolonged teamwork that is not always available in public health settings. In addition, Behavioral Therapy is not always accepted. We describe a new intensive and sustainable family-based, Therapeutic Education program for childhood obesity. METHODS: Controlled clinical study: a family-based Therapeutic Education program without dietetic prescription involving overweight and obese children/adolescents, without evident psychological troubles, and their families. The program consisted of three clinical and therapeutic education sessions, carried out by a single physician. Further sessions were carried out every six months in the first year and then every year. STUDY POPULATION: 190 overweight children, 85 treated with a therapeutic education program (45 males and 40 females, mean age of 10.43 +/- 3) with an average BMI% of 154.72 +/- 19.6% and 105 matched children, treated with traditional dietary approach.Children's Body Mass Index (BMI) % and BMI Standard Deviation Score measured at baseline and after a three year-follow-up, were compared. Statistical tests: ANOVA-RM (repeated measures) controlled for distribution by Kolmogorov-Smirnov, Bartlett's test or correspondent non-parametric procedures, X2 tests or Fisher's exact test and simple linear regression. RESULTS: After a follow-up of 2.7 +/- 1.1 years, 72.9% of the children who followed the Therapeutic Education Program obtained a BMI% reduction, compared to 42.8% of children who followed the traditional dietary treatment. Weight reduction was good in moderately obese children and in the severely obese. In addition, a smaller proportion of children treated with therapeutic education had negative results (BMI increase of >10%) compared to those treated with dietary approach (11.8% vs. 25.7%); finally, periodic phone calls reduced the drop-out rate in the therapeutic education group. CONCLUSION: These results indicate the efficacy and sustainability of the Therapeutic Education program, that was completely carried out by a single pediatrician; in addition, it met with an elevated participant acceptance, suggesting a convenient therapeutic solution for skilled pediatricians and selected obese children, when Behavioral Therapy is not available or teamwork is poor.

Circadian and seasonal variation of migraine attacks in children.

OBJECT: To investigate the rhythmicity of migraine episodes without aura in a pediatric population. METHODS: Time of occurrence of 2517 migraine attacks in 115 children was recorded, by means of a diary, both by hourly and monthly intervals. RESULTS: A significant circadian variation, characterized by a peak in the afternoon (P < .001) and one in the early morning (P= .002) was found. A seasonal peak was also observed between November and January, while a nadir was observed in July. CONCLUSIONS: The clustering of attacks in the morning and midday and in autumn-winter, with a minimum frequency in July, suggests that school activities may represent an important cause of migraine.