Masuji Hattori

Vitamins D and K in the Treatment of Osteoporosis Secondary to Graft-versus-Host Disease following Bone-Marrow Transplantation

We report a case of secondary osteoporosis treated with a combination of vitamins D3 and K2, administered orally. A 13-year-old male, diagnosed with highly differentiated acute myelogenous leukaemia, received an allogeneic bone-marrow transplantation. Chronic graft-versus-host disease persisted, thereafter, in the form of severe diarrhoea, rash and allergic conjunctivitis. Since the patient was then at risk from osteoporosis secondary to calcium malabsorption caused by the diarrhoea, dual-energy X-ray absorptiometry and ultrasound analysis were used to measure bone mineral density and bone stiffness, respectively. Both measurements were markedly lower than the average values from patients of matched age, gender and physical characteristics. The osteoporosis did not respond to active vitamin D3 0.1 μg/kg once daily, but when this therapy was combined with vitamin K2 15 mg once daily, an increase in bone mineral density and bone stiffness was observed. In conclusion, vitamin D3 and K2 combination therapy merits further evaluation for the treatment of various types of secondary osteoporosis, including steroid-induced osteoporosis.

IgA nephropathy associated with Nail–Patella syndrome in a 7-year-old girl

Osteo-Onychodysplasia (HOOD), is a rare pleiotropic disorder exhibiting autosomal dominant inheritance, defined by the association of nail dysplasia, skeletal abnormalities and renal lesions. Although the essential features and useful markers for the diagnosis of NPS are nail hypoplasia or dysplasia and absent or hypoplastic patella, the renal involvement is considered the most serious component and the cause of lethality of this syndrome. Many researchers have therefore emphasized the nephropathy of NPS. Of the 123 cases of NPS reviewed by Meyrier et al., renal involvement occurred in more than 60% and was manifested mainly by proteinuna and intermittent nephrotic syndrome.1 Fifteen percent of the total cases progressed to end-stage renal failure. We have noted that several isolated previous reports on Goodpasture’s syndrome, Membranous nephropathy and Vasculitis combined with NPS.1–3 In this report, we describe another rare association of IgA nephropathy and NPS in a 7-year-old Japanese girl.

Development of ultra-deep targeted RNA sequencing for analyzing X-chromosome inactivation in female Dent disease

The pattern of X-chromosome inactivation (XCI) can affect the clinical severity of X-linked disorders in females. XCI pattern analysis has been conducted mainly by HUMARA assay, a polymerase chain reaction-based assay using a methylation-sensitive restriction enzyme. However, this assay examines the XCI ratio of the androgen receptor gene at the genomic DNA level and does not reflect the ratio of either targeted gene directly or at the mRNA level. Here, we report four females with Dent disease, and we clarified the correlation between XCI and female cases of Dent disease using not only HUMARA assay but also a novel analytical method by RNA sequencing. We constructed genetic analysis for 4 female cases showing high level of urinary low-molecular-weight proteinuria and their parents. Their XCI pattern was analyzed by both HUMARA assay and an ultra-deep targeted RNA sequencing of the CLCN5 gene using genomic DNA and mRNA extracted from both leukocytes and urine sediment. All four cases possessed pathogenic variants of the CLCN5 gene. XCI analysis revealed skewed XCI in only two cases, while the other two showed random XCI. All assay results of HUMARA and targeted RNA sequencing in both leukocytes and urinary sediment were clearly identical in all four cases. We developed a novel XCI analytical assay of ultra-deep targeted RNA sequencing and revealed that skewed XCI explains the mechanism of onset of female Dent disease in only half of such cases.