Tadashi Asami

Mental Development of Infants With Congenital Hypothyroidism: A Longitudinal Study

The purpose of this study was to assess the relationship between the clinical findings before starting treatment and the development quotient in children treated for congenital hypothyroidism. Patients with congenital hypothyroidism (n = 129) were divided into favorable and unfavorable groups according to intellectual performance. Children with congenital hypothyroidism generally have a similar intellectual outcome to that of healthy children. However, a low birth weight, the presence of complications, and a high serum thyroid-stimulating hormone value are the risk factors for unfavorable cases, who consistently have a development quotient score of less than 100.

Long-term follow-up study for a patient with Floating-Harbor syndrome due to a hotspot SRCAP mutation.

Floating–Harbor syndrome (FHS) is a rare autosomal dominant disorder characterized by short stature, skeletal malformations, speech delay, and dysmorphic facial appearance. Recently, mutations in SRCAP encoding a coactivator for cAMP‐response element binding protein (CREB)‐binding protein have been identified in small number of patients with FHS. Here, we report on long‐term follow‐up data of a male patient with a SRCAP mutation. The patient presented with mild hypothyroidism and renal hypouricemia, in addition to several FHS‐compatible features including growth impairment, cognitive disability, facial dysmorphisms, and hypertension. He showed delayed bone age from infancy to 9 years of age and markedly accelerated bone age with the formation of cone‐shaped epiphyses and early epiphysial fusions after the onset of puberty. His pubertal sexual development was almost age appropriate. Two‐year treatment with growth hormone (GH) did not significantly improve the growth velocity. Molecular analysis identified a de novo heterozygous nonsense mutation (p.R2444X) in the last exon of SRCAP, which has been most common mutation detected in patients from other ethnic groups. These results indicate that perturbed skeletal maturation from infancy through adolescence is a characteristic feature in patients with SRCAP mutations. Furthermore, our data imply that GH therapy exerted only a marginal effect on the growth of this patient, and that renal hypouricemia may be a novel complication of FHS.

H62L Mutation of CYP21A2 Identified in the Non-classical Form of 21-Hydroxylase Deficiency

Neonatal mass screening for congenital adrenal hyperplasia (CAH) has been performed in Japan since 1989. Steroid 21-hydroxylase deficiency (21-OHD) represents about 95% of CAH patients and is traditionally divided into three forms, severe classical salt-wasting (SW), simple virilizing (SV) and the milder non-classical (NC) form. Very rare cases of the NC form have been detected because of elevated 17-hydroxyprogesterone (17-OHP) levels at neonatal mass screening in Japan (1). The estimated rate of detection of the NC form by mass screening seems to be low (1:1,100,000) (1). This disease is caused by deletions or mutations of CYP21A2. In Japan, the P30L mutation appears more likely to be associated with Japanese NC patients (1). Here, we report a rare H62L mutation with the NC form in a Japanese 21-OHD patient.

A study of the etiology of transient congenital hypothyroidism in Niigata Prefecture, Japan

Background Several conditions have been known to causetransient congenital hypothyroidism (TCH), including transplacental passage of TSH receptor blocking antibody (TSBAb), maternal antithyroid drug usage, iodine deficiency, iodine excess, fetal prematurity and inactivatingDUOX2mutations. However, the underlying etiology of TCH is not determined in some cases. In this study, we conducted the first systematic investigation on the etiology of TCH, using screening population-based cohort in Niigata Prefecture, Japan.

Longitudinal Growth of the Short Bones of the Hand in a Girl with Pseudohypoparathyroidism Type Ia

Brachydactyly is a common feature of pseudohypoparathyroidism (PHP) type Ia. We studied the longitudinal growth of the short bones in the hand of a 15-yr-old girl with PHP type Ia who had been followed for congenital hypothyroidism. Radiographs of the hand of the patient, who had been X-rayed every year since 2 yr of age, were studied. She showed cone-shaped epiphyses of the hand at 2 yr of age before showing brachydactyly. At 4 yr of age, she showed brachydactyly and an advanced bone age, and some short bones were prematurely fused at 6 yr of age. The short bones without cone-shaped epiphyses were also short as a result of a disturbance of the longitudinal bone elongation. In conclusion, the brachydactyly of PHP type Ia is thus considered to be caused by both early epiphyseal fusion with cone-shaped epiphyses and a disturbance of the longitudinal bone elongation.