Valentina Fattorusso

Celiac disease in type 1 diabetes mellitus

Celiac Disease (CD) occurs in patients with Type 1 Diabetes (T1D) ranging the prevalence of 4.4-11.1% versus 0.5% of the general population. The mechanism of association of these two diseases involves a shared genetic background: HLA genotype DR3-DQ2 and DR4-DQ8 are strongly associated with T1D, DR3-DQ2 with CD. The classical severe presentation of CD rarely occurs in T1D patients, but more often patients have few/mild symptoms of CD or are completely asymptomatic (silent CD). In fact diagnosis of CD is regularly performed by means of the screening in T1D patients. The effects of gluten-free diet (GFD) on the growth and T1D metabolic control in CD/T1D patient are controversial. Regarding of the GFD composition, there is a debate on the higher glycaemic index of gluten-free foods respect to gluten-containing foods; furthermore GFD could be poorer of fibers and richer of fat. The adherence to GFD by children with CD-T1D has been reported generally below 50%, lower respect to the 73% of CD patients, a lower compliance being more frequent among asymptomatic patients. The more severe problems of GFD adherence usually occur during adolescence when in GFD non compliant subjects the lowest quality of life is reported. A psychological and educational support should be provided for these patients.

Thiamine responsive megaloblastic anemia: a novel SLC19A2 compound heterozygous mutation in two siblings

Thiamine responsive megaloblastic anemia (TRMA) is an autosomal recessive disease caused by loss of function mutations in the SLC19A2 gene. TRMA is characterized by anemia, deafness, and diabetes. In some cases, optic atrophy or more rarely retinitis pigmentosa is noted. We now report two sisters, the eldest of which presented to a different hospital during childhood with sensorineural deafness, which was treated with a hearing prosthesis, insulin requiring diabetes, retinitis pigmentosa, optic atrophy, and macrocytic anemia. These features initially suggested a clinical diagnosis of Wolfram syndrome (WS). Therapy with thiamine was initiated which resulted in the resolution of the anemia. The younger sister, who was affected with sensorineural deafness, was referred to our hospital for non‐autoimmune diabetes. She was found to have macrocytosis and ocular abnormalities. Because a diagnosis of TRMA was suspected, therapy with insulin and thiamine was started. Sequencing analysis of the SLC19A2 gene identified a compound heterozygous mutation p.Y81X/p.L457X (c.242insA/c.1370delT) in both sisters. Non‐autoimmune diabetes associated with deafness and macrocytosis, without anemia, suggests a diagnosis of TRMA. Patients clinically diagnosed with WS with anemia and/or macrocytosis should be reevaluated for TRMA.

Glucose derangements in very young children with cystic fibrosis and pancreatic insufficiency.

Cystic fibrosis–related diabetes (CFRD) is considered the most common comorbidity in patients affected by cystic fibrosis (CF), with a prevalence increasing with age (1). Recently, more attention has been turned to other less severe glucose metabolism derangements (GMD), since prediabetes may be related to increased morbidity (1), and early treatment may improve the clinical course in patients with CF (2). According to recent guidelines released by the Cystic Fibrosis Foundation, the American Diabetes Association, and the Pediatric Endocrine Society, the oral glucose tolerance test (OGTT) is recommended yearly in patients with CF over 10 years of age (3). Some authors recommend annual OGTT after the age of 6 years in CF patients with pancreatic insufficiency (4). In …

Thiamine-Responsive Megaloblastic Anemia Syndrome

Thiamine-responsive megaloblastic anemia (TRMA) syndrome (OMIM No. 249270) is an autosomal recessive disorder and an example of a rare form of monogenic diabetes coexisting with anemia and deafness. T

Psoriasis in children with type 1 diabetes: A new comorbidity to be considered?

Type 1 diabetes mellitus (T1DM) is the most common endocrine disease of childhood, due to an immune-mediated destruction of insulin-producing pancreatic b-cells. Comorbidities are frequent in T1DM and can severely affect clinical management [1]. To date, vitiligo and alopecia areata are the only described cutaneous comorbidities associated with T1DM, while psoriasis is usually associated with type 2 diabetes mellitus [2]. Psoriasis is an inflammatory skin disease affecting up to 2% of children in Europe and, in particular, 2.1% in Italy [3, 4]. To date, psoriasis prevalence in T1DM is not well known. Aim of our study was to investigate prevalence of psoriasis in T1DM patients in pediatric age.

Cerebral Accidents in Pediatric Diabetic Ketoacidosis: Different Complications and Different Evolutions

Diabetic ketoacidosis (DKA) may be associated with neurologic complications: the most common is cerebral edema while the risk of venous and arterial stroke is rare. There is a pathogenetic link between DKA, hypercoagulability and stroke, whose risk is underestimated by clinicians. Our cases present a wide spectrum of cerebral accidents during DKA, the first one being diffuse cerebral edema, the second one venous stroke after 5 days of DKA resolution, while the third one multifocal edema suspected to be extrapontine myelinolysis although without electrolyte imbalance. Our cases suggest that DKA requires very accurate treatment, particularly at an early age, and it can be complicated by cerebral accidents even with appropriate medical care.

Screening of glucose metabolism derangements in pediatric cystic fibrosis patients: how, when, why.

Diabetes mellitus is the most common comorbidity in cystic fibrosis (CF), occurring in a variable number of children and adolescents. Glucose metabolism derangements (GMDs) are responsible for a negative impact on the general health status of CF patients. Screening of GMDs is important since the youngest age and should be performed by means of OGTT, including its intermediate times, that could detect other non-traditional GMDs. Insulin treatment, administered before overt diabetes, could be beneficial in reducing the number of pulmonary infections, in improving both pulmonary function and nutritional status. Early screening of GMDs in pediatric age can exert an important preventing role regarding all aspects of health status of patients with CF.

Mulibrey nanism: Two novel mutations in a child identified by Array CGH and DNA sequencing

In childhood, several rare genetic diseases have overlapping symptoms and signs, including those regarding growth alterations, thus the differential diagnosis is sometimes difficult. The proband, aged 3 years, was suspected to have Silver–Russel syndrome because of intrauterine growth retardation, postnatal growth retardation, typical facial dysmorphic features, macrocephaly, body asymmetry, and bilateral fifth finger clinodactyly. Other features were left atrial and ventricular enlargement and patent foramen ovale. Total X‐ray skeleton showed hypoplasia of the twelfth rib bilaterally and of the coccyx, slender long bones with thick cortex, and narrow medullary channels. The genetic investigation did not confirm Silver–Russel syndrome. At the age of 5 the patient developed an additional sign: hepatomegaly. Array CGH revealed a 147 kb deletion (involving TRIM 37 and SKA2 genes) on one allele of chromosome 17, inherited from his mother. These results suggested Mulibrey nanism. The clinical features were found to fit this hypothesis. Sequencing of the TRIM 37 gene showed a single base change at a splicing locus, inherited from his father that provoked a truncated protein. The combined use of Array CGH and DNA sequencing confirmed diagnosis of Mulibrey nanism. The large deletion involving the SKA2 gene, along with the increased frequency of malignant tumours in mulibrey patients, suggests closed monitoring for cancer of our patient and his mother. Array CGH should be performed as first tier test in all infants with multiple anomalies. The clinician should reconsider the clinical features when the genetics suggests this.

Type 1 Diabetes Mellitus and Co-Morbidities

2.1 Genetic associations Patients with type 1 diabetes (T1D) have an increased risk of other autoimmune conditions, such as autoimmune thyroid disease (AIT), celiac disease (CD), Addison’s disease (AD) and vitiligo. These diseases are associated with organ-specific autoantibodies: AIT with thyroid peroxidase (TPO) and thyroglobulin autoantibodies (TG), CD with endomysial (EMA) and transglutaminase (TTG) autoantibodies, and AD with adrenal autoantibodies. Using these autoantibodies, organ-specific autoimmunity may be often detected before the development of clinical disease, in order to prevent significant morbidity related to unrecognized disease (Barker, 2006). The probable mechanism of these associations involves a shared genetic background (Myśliwiec et al., 2008; Smyth et al., 2008). The majority of autoimmune endocrinopathies, including T1D, are inherited as complex genetic traits. Multiple genetic and environmental factors interact with each other to confer susceptibility to these disorders. Genetic risk factors associated with T1D, ATD, CD and AD include HLA genes and non-HLA genes.