Endocrinological Features of Hartsfield Syndrome in an Adult Patient With a Novel Mutation of FGFR1.

Hartsfield syndrome (HS: OMIM 615465) is a rare congenital disease associated with a mutation of the fibroblast growth factor receptor 1 gene (FGFR1) with the main features of holoprosencephaly and ectrodactyly. Patients with HS also present with endocrinological deficits, such as isolated hypogonadotropic hypogonadism and central diabetes insipidus. Although there are several studies on infancy/childhood history, there is no study of infant/childhood/adolescent/young adult HS natural history and endocrinological findings. Here, we report a male patient with HS associated with a novel de novo FGFR1 mutation (c. 1868A > C). The endocrinological profile was evaluated at ages 1 and 31 years. This long-term follow-up study highlights functional changes in the posterior pituitary gland and features of bone metabolism disorder. We also describe the anterior pituitary function. To our knowledge this is the first description of the natural history of an HS patient through birth to young adult age. Although the HS infants reported in the literature develop central diabetes insipidus, little is known about the serial changes in pituitary gland function during growth in HS patients. In this study we describe an adult patient with HS who showed improvement of hypernatremia during early adulthood. In addition, we emphasize the importance of prevention and treatment of osteoporosis in HS.

Association of variation range in glycated albumin (GA) with increase but not decrease in plasma glucose: implication for the mechanism by which GA reflects glycemic excursion.

OBJECTIVES: HbA1c mainly reflects mean plasma glucose (PG), whereas glycated albumin (GA) reflects glycemic excursion in addition to mean PG; the mechanism of the difference between HbA1c and GA is unknown. We hypothesized that a transient increase in PG irreversibly produces stable GA unlike HbA1c. To prove this hypothesis, we investigated diurnal variations in PG, HbA1c, #C fraction (a fraction containing unstable HbA1c and modified hemoglobin on HPLC) and GA in diabetic patients. DESIGN AND METHODS: Sixteen diabetic patients with poor glycemic control were enrolled in this study. Blood sampling was performed before and after each meal, before bedtime, and before breakfast on the following day; PG, HbA1c, #C fraction, and GA were measured. The variations of these indicators were compared with those in PG. RESULTS: HbA1c showed almost no change regardless of diurnal glycemic variation. Variation range in #C fraction significantly correlated with variation range in PG when PG increased (R=0.746, p<0.0001) and decreased (R=0.271, p=0.035). On the other hand, variation range in GA significantly correlated with variation range in PG when PG increased (R=0.322, p=0.021), but not when PG decreased (R=0.090, p=0.493). CONCLUSIONS: We observed that variation range in GA significantly correlated with variation range in PG when PG increased but not when PG decreased for the first time. It is considered that GA reflects glycemic excursion through this phenomenon.