Genetic and enzymatic analysis for two Japanese patients with idiopathic infantile arterial calcification.

Idiopathic infantile arterial calcification (IIAC) is a life-threatening disorder in young infants. Cardiovascular symptoms are usually apparent within the first month of life. The symptoms are caused by calcification of large and medium-sized arteries, including the aorta, coronary arteries, and renal arteries. Most of the patients die by 6 months of age because of heart failure. Recently, homozygous or compound heterozygous mutations for the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene were reported as causative for the disorder. ENPP1 regulates extracellular inorganic pyrophosphate (PPi), a major inhibiter of extracellular matrix calcification. Two Japanese patients with IIAC were studied. One, from first-cousin parents, showed a typical clinical course. The onset in the second patient was late. Both of the patients were clinically compatible for IIAC; arterial calcification was shown, and hypertension was prominent. We sequenced all the exons and exon-intron boundaries of the gene and measured nucleotide pyrophosphohydrolase (NPPH) activity of ENPP1. Homozygous Arg730Stop was detected in the typical IIAC patient. The mutation was a novel nonsense mutation and not detected in 60 healthy controls. His NPPH activity was 4% of normal. On the other hand, the late-onset patient was not shown to have any mutations. NPPH activity in this patient was 70% of normal. We confirmed that ENPP1 was also responsible for the Japanese patient with IIAC. The atypical late-onset phenotype may not be associated with ENPP1 abnormalities. IIAC is considered to be a clinically and genetically heterogeneous disorder.

Gonadal Function in 15 Patients Associated with WT1 Gene Mutations.

Denys-Drash syndrome (DDS) and Frasier syndrome (FS) are caused by mutations of the WT1 gene. These disorders are characterized by renal disease, abnormality of male sex differentiation, and Wilms' tumor and gonadoblastoma. There have been few reports on gonadal function in a large series of patients with mutations of the WT1 gene. Here, we evaluated the relation between gonadal function and the phenotype of external genitalia in 15 Japanese patients with WT1 mutations. We confirmed three sets of information. First, if a diagnosis of DDS and FS is arrived at by genetic analysis, there are some overlaps in the phenotypes of external genitalia and renal complications. Second, the responses of serum T for the human CG (HCG) loading test coincided with the phenotype of external genitalia in both DDS and FS, except two patients. One DDS patient had male type external genitalia with a low level of serum T response, and one FS patient had complete female external genitalia despite a definite serum T response to HCG stimulation. Third, four FS patients had incomplete development of pubic hair, together with low DHEA-S levels.

[Osteoporosis in anorexia nervosa].

Anorexia nervosa (AN) has recently become one of common disorders in adolescent girls. A chronic course of AN is related to morbidity, with one of the most serious medical complications being severe osteopenia. The prevalence of osteoporosis is estimated to be 40 % in AN during the follow up. The incidence of bone fracture in AN after the recovery of body weight is reported to be two to seven higher than that in healthy age-matched controls. Because adolescence is a critical time in terms of acquisition of peak bone mass, osteopenia during this time may be permanent. Adult woman with adolescence-onset AN has lower bone mineral density than that with adult-onset AN. In addition, bone mineral density (BMD) of AN has been shown to be influenced by several factors, including reduced body weight due to malnutrition, intake of calcium and vitamin D, and duration of estrogen deficiency. Among them, body weight is known to be the most important prognostic factor, both in a short and long period of years. Thus, medical doctor should monitor BMD in patients with AN throughout their life.