A case of Dent disease type 2 with large deletion of OCRL diagnosed after close examination of a school urinary test.

A 7-year-old boy visited our hospital for a detailed examination of proteinuria identified in a school urinary test. He had short stature, misaligned teeth, and mild intellectual disability. A urinary examination identified mild proteinuria and extremely high levels of beta-2 microglobulin. On blood examination, his protein, albumin, and creatinine levels were found to be normal; however, his lactate dehydrogenase and creatinine phosphokinase levels were slightly elevated. Upon histological examination, no abnormalities in glomeruli or tubules were found. Considering these results, we diagnosed our patient with Dent disease type 2 (DD2). Although the whole exome sequencing revealed large deletion of OCRL, which was seen only in Lowe syndrome and not in DD2 previously, our final diagnosis for the patient is DD2. A phenotypic continuum exists between Dent disease and Lowe syndrome, and several factors modify the phenotypes caused by defects in OCRL. Although patients have thus far been diagnosed with DD2 or Lowe syndrome on the basis of their symptoms, accumulation and analysis of cases with OCRL defects may hereafter enable more accurate diagnoses.

Leucine-rich alpha-2-glycoprotein 1 and angiotensinogen as diagnostic biomarkers for Kawasaki disease.

OBJECTIVE: Kawasaki disease (KD) is a systemic vasculitis in childhood that can lead to coronary artery lesions (CALs). Although early diagnosis and treatment is important for preventing KD patients from development of CALs, diagnosis depends on the clinical features of KD. We studied the usefulness of leucine-rich alpha-2-glycoprotein 1 (LRG1) and angiotensinogen (AGT), previously reported as KD-related proteins, for KD diagnosis and estimation of intravenous immunoglobulin (IVIG) efficacy. METHODS: We undertook a prospective cohort study with patients having two or more KD symptoms in multiple centers in Japan, between July 2017 and February 2019. RESULTS: Two hundred forty-two patients were included. In multivariable analysis, one unit increase in LRG1 was associated with higher odds of KD diagnosis (Odds ratio [OR] 1.02 [95% confidence interval (CI) 1.001-1.03]). Double-positivity for AGT (≥ 26 µg/mL) and LRG1 (≥ 123.5 µg/mL) was an independent biomarker for KD diagnosis in both the total cohort and the subgroup of patients with two to four KD symptoms (OR 5.01 [95% CI 1.86-13.50] and 3.71 [95% CI 1.23-11.16], respectively). There was no association between LRG1/AGT and IVIG efficacy. CONCLUSION: Double-positivity for LRG1 and AGT is an biomarker for KD diagnosis, especially useful in diagnosing incomplete KD from non-KD. Future studies with larger cohorts should seek to determine whether LRG1 and AGT are valuable as definitive data referred at the diagnosis of KD and for estimating the risk of CALs.

Cause of acute encephalitis/encephalopathy in Japanese children diagnosed by a rapid and comprehensive virological detection system and differences in their clinical presentations.

BACKGROUND: Acute encephalitis/encephalopathy (AE/E) is a rare and severe complication of common childhood infections; however, a treatment strategy based on clinical and pathological evidence has not been established. METHODS: The clinical data and aetiological results using a rapid and comprehensive virological detection system of 62 Japanese children diagnosed with AE/E from 2010 to 2014 were collected. We assessed clinical differences between causes and effectiveness of our multiplex PCR system to establish a pathogen-based treatment strategy for AE/E. RESULTS: Suspected causes were detected in 84% of patients, and our multiplex PCR system contributed to diagnosing 38% of the patients. Furthermore, a negative virus PCR might be important for inferring underlying disease. Most cases were triggered by human herpes virus (HHV) 6/7 (32%) and influenza virus (24%). The causes of AE/E depended on age (p=0.00089) but not on sex (p=0.94). The median age of HHV6/7-associated AE/E was 2.3years, which is lower than the median ages of AE/E associated with other viruses. Major initial treatments were pulse steroid therapy (83.9%) and acyclovir (71%). Most of the patients in this study had good prognoses: 77% recovered without neurological sequalae. CONCLUSIONS: Our virological detection system was useful for detecting the cause of AE/E, and may also contribute to construction of pathogen-based treatment strategies for AE/E. Our data indicated the possibility that early intervention with pulse steroid therapy could be effective for treating AE/E. Further investigation for selection of antiepileptic drugs and additional therapies might be required to prevent progression of AE/E.

Early activation does not translate into effector differentiation of peripheral CD8T cells during the acute phase of Kawasaki disease.

Early diagnosis of acute Kawasaki disease (KD), lying in the spectrum between infectious and autoimmune diseases, can be difficult. To clarify the role of peripheral CD8T cells in KD, we examined their activation, proliferation, maturation, and effector function by four-color flow cytometry. Compared to healthy/febrile controls, acute KD patients showed striking increase in early activation marker CD69(+)CD8T cells and maturation subsets, but HLA-DR(+)CD8T cells representing late activation did not increase. Although Ki67(+)CD8T cells reflecting ongoing cell division increased in acute KD and febrile controls, absolute numbers of CD8T cells and maturation subsets decreased in acute KD versus healthy controls. Effector cells were lower in acute than in convalescent KD. Perforin(+)CD8T cells, denoting cytolytic activity, were lower in KD patients versus febrile controls. CD69(+)CD8T cells increase in acute KD but effector differentiation is absent. CD69(+)CD8T cells could be a marker to determine disease progression, treatment response, and convalescence in acute KD.