Eculizumab in Adolescent Patients With Refractory Generalized Myasthenia Gravis: A Phase 3, Open-Label, Multicenter Study.

BACKGROUND: This study evaluated the efficacy and safety of eculizumab, a terminal complement C5 inhibitor, in juvenile generalized myasthenia gravis (gMG). METHODS: Adolescents aged 12 to 17 years with refractory anti-acetylcholine receptor (AChR) antibody-positive gMG received eculizumab (weekly induction [one to two doses of 600 mg or four doses of 900 mg] followed by maintenance doses [300 to 1200 mg] every two weeks for up to 26 weeks) in a phase 3, open-label multicenter study (NCT03759366). Change from baseline to week 26 in Quantitative Myasthenia Gravis (QMG) total score (primary end point) and secondary end points including Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score, Myasthenia Gravis Composite score, Myasthenia Gravis Foundation of America postintervention status, EuroQol 5-Dimensions (Youth) and Neurological Quality-of-Life Pediatric Fatigue questionnaire scores, as well as pharmacokinetics, pharmacodynamics, and safety, were recorded. RESULTS: Eleven adolescents (mean ± S.D. age 14.8 ± 1.8 years) were enrolled; 10 completed the primary evaluation period. Least-squares mean changes from baseline at week 26 were -5.8 (standard error [SE] 1.2; P = 0.0004) for QMG total score and -2.3 (SE 0.6; P = 0.0017) for MG-ADL total score. Overall, the primary and all secondary efficacy end point analyses met statistical significance from the first assessment and were sustained throughout. Complete terminal complement inhibition was sustained through 26 weeks in all patients. Treatment-emergent adverse events were all mild/moderate and predominantly unrelated to eculizumab. CONCLUSIONS: Eculizumab was effective in reducing disease burden and was well tolerated in adolescents with refractory AChR antibody-positive gMG.

Effect of proteinuria at relapse on shear wave velocity assessed using ultrasound elastography in children with idiopathic nephrotic syndrome.

PURPOSE: Shear wave velocity (SWV) is an ultrasound elastography technique that provides much information for kidney disease assessment. However, the factors that alter SWV are not fully understood; it is unclear whether the variation in SWV seen in proteinuria associated with disease progression is due to tissue or proteinuria. This study investigated the effect of proteinuria on SWV. METHODS: This prospective observational study compared SWV at remission with SWV at relapse in children treated for idiopathic nephrotic syndrome (INS) between April 2020 and December 2023. All relapses without oral steroids during the observation period were measured. SWV at remission was defined as the date closest to relapse during which repeated measurements were taken approximately every 3 months after steroid discontinuation. RESULTS: Eight patients were treated for INS with a median observation period of 21.9 months (11.8-27.1). Of the 15 relapses, five that met the definition were considered for the study. The median interval between the measurement at relapse and remission was 40 days (11-55). SWV was significantly lower at relapse than remission (2.40 ± 0.20 m/s vs. 2.14 ± 0.15 m/s, P < 0.01). CONCLUSIONS: SWV decreased in the presence of severe proteinuria at relapse compared to the remission measurements. Although more cases need to be studied, the decrease in SWV may reflect the mechanism by which protein leaks into the urine, not just a direct change caused by the presence of proteinuria.

A case of rapid avacopan-induced liver injury in pediatric granulomatosis with polyangiitis.

Children with anti-neutrophil cytoplasmic antibody-associated vasculitis benefit immensely from avacopan as it reduces the requirement for steroids. However, descriptions of adverse drug reactions in children are lacking, and the dosage and follow-up intervals are unclear. A 10-year-old boy with initial granulomatosis and polyangiitis presented with diffuse pulmonary hemorrhage. Rituximab and 30 mg avacopan were administered twice daily as induction therapy following methylprednisolone pulse therapy. However, sudden liver function test abnormalities were observed on day 31 of avacopan treatment, despite liver enzyme levels being within the normal range 5 days earlier. A drug-induced lymphocyte stimulation and various infectious disease tests yielded negative results. Discontinuation of rituximab and avacopan resulted in improved liver function; no change in the Birmingham Vasculitis Activity Score during liver function test abnormalities was observed. Avacopan-associated abnormalities in liver function tests suggest that drug-induced liver injury may occur rapidly in children, and appropriate dosing strategies should be reconsidered.

Case Report: Tuberous sclerosis complex-associated hemihypertrophy successfully treated with mTOR inhibitor sirolimus.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by a mutation in either of the two tumor suppressor genes, TSC1 and TSC2. Due to dysregulated activity of the mammalian target of rapamycin (mTOR) pathway, hamartomas or benign tumors frequently occur in many organs and are often treated with mTOR inhibitors. Hemihypertrophy is a rare complication of TSC. Although not being a tumor, progressive overgrowth of the affected limb may cause cosmetic and functional problems, for which the efficacy of mTOR inhibitors has not been reported previously. We herein report a case of TSC-associated hemihypertrophy. In this case, genetic studies revealed TSC1 loss of heterozygosity as the cause of hemihypertrophy. Clinically, pharmacological treatment with an mTOR inhibitor sirolimus successfully ameliorated cosmetic and functional problems with no intolerable adverse effects.

Pathological Factors Affecting the R2* Values of the Kidney in Blood Oxygenation Level-dependent MR Imaging: A Retrospective Study.

PURPOSE: Despite the usefulness of blood oxygenation level-dependent (BOLD) MRI in assessing glomerulonephritis activity, its relationship with histological findings remains unclear. Because glomerulonephritis presents multiple complex injury patterns, analysis of each pattern is essential. We aimed to elucidate the relationship between the histological findings of the kidney and BOLD MRI findings in mesangial proliferative glomerulonephritis. METHODS: Children under 16 years of age diagnosed with mesangial proliferative glomerulonephritis by kidney biopsy at our university hospital between January 2013 and September 2022 were included in this study. Cortical and medullary spin relaxation rate (R2*) values were measured using BOLD MRI at 3T within two weeks before and after the kidney biopsy. The R2* values, including the fluctuations with low-dose oxygen administration, were retrospectively examined in relation to the cortical (mesangial proliferation, endothelial cell proliferation, crescent, sclerosis, and fibrosis) and medullary findings (fibrosis). RESULTS: Sixteen times kidney biopsies were performed for glomerulonephritis during the study period, and one patient was excluded because of comorbidities; the remaining 14 patients included six boys with a mean age of 11.9 ± 3.5 years at the BOLD examination. None of the patients had medullary fibrosis. Among the kidney tissue parameters, only sclerosis showed a significant correlation with R2* values: medulla with R2* values under atmospheric pressure (r = 0.53, P < 0.05) and cortex with the rate of change in R2* values with low-dose oxygen administration (r = -0.57, P < 0.03). In the multiple regression analysis, only sclerosis was an independent contributor to the change in R2* values with oxygen administration in the cortex (regression coefficient -0.109, P < 0.05). CONCLUSION: Since the R2* values reflect histological changes in the kidney, BOLD MRI may facilitate the evaluation of mesangial proliferative glomerulonephritis, potentially reducing the patient burden.

A Case of Shear Wave Velocity Reflecting the Disease Activity in Glomerulonephritis.

Ultrasound elastography can measure tissue elasticity using the shear wave velocity (SWV). Evaluating disease activity with elastography instead of renal biopsy may be less invasive. However, to the best of our knowledge, although there are studies comparing different glomerular diseases using SWV, there are no reports that have measured glomerulonephritis longitudinally from the acute phase of the disease. This study aimed to assess whether SWV reflects disease activity in glomerulonephritis, and we continued to observe children with post-streptococcal acute glomerulonephritis (PSAGN) from the acute phase to over a year later. In this case, a 6-year-old boy diagnosed with PSAGN had impaired renal function, and was admitted and tested. He was placed in a prone resting position and measurements were taken from the back. SWV was measured ≥50 times at each examination, and the mean was calculated when the net amount of effective SWV was ≥50%. The tests were performed once in the acute phase and thrice during the recovery phase for 13 months. SWV was found to be significantly lower in the recovery period than during the disease onset, and continued to stay lower at each test during the recovery period (P < 0.02). In conclusion, this indicated that SWV fluctuated similarly to the disease activity of glomerulonephritis; therefore, we suggest using SWV measurement to estimate the disease activity in glomerulonephritis in children. Although more clinical cases are needed, SWV measurement is a noninvasive and reproducible imaging modality to estimate the disease activity in glomerulonephritis.

Glomeruli Count and Arterial Injury in Real-Time Ultrasound-Guided Needle Kidney Biopsy Specimens: Adequacy of Three Approaches for Pig Kidneys.

INTRODUCTION: Real-time ultrasound-guided percutaneous kidney biopsy is essential for diagnosis and treatment planning; nonetheless, the optimal puncture approach has yet to be established. In vivo, performing different approaches on the same patient at once is not possible. This study aimed to determine the impact of different approaches on the number of obtained glomeruli and their potential to cause arterial injury using pig kidneys, which are similar to humans. METHODS: A total of 120 pig kidneys (60 right-sided kidneys and 60 left-sided kidneys) for research were obtained from a slaughterhouse. The specimens were collected from the lower pole on the sagittal plane of the kidney using three different approaches on the same kidney: caudocranial approach, caudal to cranial; craniocaudal approach, cranial to caudal; and vertical approach, through the surface cortex. Five blinded pediatric nephrologists assessed the number of glomeruli and arterial injuries. RESULTS: Overall, 360 specimens were collected from the kidneys through biopsy using a 16-gauge needle (mean vertical kidney length, 11.2 ± 0.7 cm; mean depth, 3.47 ± 0.23 cm). No significant difference in the incidence of arterial injury was observed between the three approaches (caudocranial vs. craniocaudal vs. vertical approaches: 78% vs. 87% vs. 87%, p = 0.14). In contrast, the vertical approach retrieved significantly more glomeruli than the caudocranial and craniocaudal approaches (caudocranial approach: 7.5 ± 2.8, craniocaudal approach: 7.8 ± 2.7, and vertical approach: 8.9 ± 3.3, p < 0.001). CONCLUSIONS: Considering its efficacy and safety profile, the vertical approach may be preferred, as more glomeruli can be obtained without increasing the incidence of arterial injury. Although the results cannot be directly extrapolated to humans due to the differences between species, they still offer important insights into the characteristics of each approach.

Estimation of the Number of Patients With Mitochondrial Diseases: A Descriptive Study Using a Nationwide Database in Japan.

BACKGROUND: To provide a better healthcare system for patients with mitochondrial diseases, it is important to understand the basic epidemiology of these conditions, including the number of patients affected. However, little information about them has appeared in Japan to date. METHODS: To gather data of patients with mitochondrial diseases, we estimated the number of patients with mitochondrial diseases from April 2018 through March 2019 using a national Japanese health care claims database, the National Database (NDB). Further, we calculated the prevalence of patients, and sex ratio, age class, and geographical distribution. RESULTS: From April 2018 through March 2019, the number of patients with mitochondrial diseases was 3,629, and the prevalence was 2.9 (95% confidence interval [CI], 2.8-3.0) per 100,000 general population. The ratio of females and males was 53 to 47, and the most frequent age class was 40-49 years old. Tokyo had the greatest number of patients with mitochondrial diseases, at 477, whereas Yamanashi had the fewest, at 13. Kagoshima had the highest prevalence of patients with mitochondrial diseases, 8.4 (95% CI, 7.1-10.0) per 100,000 population, whereas Yamanashi had the lowest, 1.6 (95% CI, 0.8-2.7). CONCLUSION: The number of patients with mitochondrial diseases estimated by this study, 3,269, was more than double that indicated by the Japanese government. This result may imply that about half of all patients are overlooked for reasons such as low severity of illness, suggesting that the Japanese healthcare system needs to provide additional support for these patients.

Effects of diurnal variation of bile acids by meal on cyclosporine A absorption.

BACKGROUND: Stabilizing blood levels with microemulsified cyclosporine A (CsA), administered in many pediatric kidney diseases, is important for effective immunosuppression and reduced nephrotoxicity. CsA is affected by total bile acids (TBAs); however, no reports have simultaneously measured both. We aimed to elucidate the hypothesized relationship between TBA levels and diurnal variation in CsA in children. METHODS: We retrospectively reviewed the medical records of children who were taking oral CsA for the treatment of kidney diseases between January 2016 and July 2021. They consumed four balanced meals and snacks during the day. CsA and TBA were measured twice, in pairs, before and at 0.5, 1, 1.5, 2, 3, and 4 h after oral administration in the morning and evening, and the four-h area under curve (AUC)0-4 of CsA and trough-to-peak ratio (TPR) of TBA were compared. RESULTS: Fifty-eight pairs were measured in total; 12 children had idiopathic nephrotic syndrome and 4 children had immunoglobulin A vasculitis with nephritis. The median age at measurement was 7.5 years and the dose of CsA was 3.8 mg/kg/day. The AUC0-4 (ng·h/mL) was significantly lower in the evening than in the morning (1,669 vs. 1,451, P < 0.001). The TPR of TBA was significantly higher in the evening than in the morning (0.14 vs. 0.25, P < 0.001). CONCLUSIONS: The low AUC0-4 and slow TBA secretion observed in the evening may be due to pediatric-specific dietary rhythms; thus, snack timing should be considered in children for stabilizing CsA levels.

Simultaneous assay of urine sepiapterin and creatinine in patients with sepiapterin reductase deficiency.

OBJECTIVES: Sepiapterin reductase deficiency (SRD) causes central nervous system symptoms due to dopamine and serotonin depletion because sepiapterin reductase plays an important role in tetrahydrobiopterin biosynthesis. SRD cannot be detected by newborn screening because of the absent hyperphenylalaninemia. To diagnose SRD biochemically, confirmation of reduced monoamine metabolites and elevated sepiapterin in the cerebrospinal fluid (CSF) has been considered necessary, because a past study showed no elevation of urine sepiapterin. Recently, however, the elevation of urine sepiapterin in SRD was reported. METHODS: We developed a fast method to measure sepiapterin and creatinine simultaneously using high-performance liquid chromatography with fluorescence and ultraviolet detection. Urine sepiapterin and creatinine were measured in three SRD patients, two SRD carriers, four SRD siblings, and 103 non-SRD patients. RESULTS: In the three SRD cases, concentrations of urine sepiapterin were 1086, 914, and 575 µmol/mol creatinine (upper limit: 101.7 µmol/mol creatinine), and were markedly higher than those in other groups. CSF sepiapterin concentration was also measured in one SRD case and it was 4.1 nmol/L (upper limit: 0.5 nmol/L). CONCLUSIONS: The simultaneous determination of urine sepiapterin and creatinine appears helpful for the diagnosis of SRD. This assay system can also be used to measure sepiapterin in the CSF.

Selenium Associates With Response to Erythropoiesis-Stimulating Agents in Hemodialysis Patients.

Introduction: Impaired response to erythropoiesis-stimulating agents (ESAs) is associated with increased mortality in patients with end-stage kidney disease. However, the underlying mechanisms are not fully elucidated. Accumulating data reveal that selenium (Se), a trace element, plays a key role in stress erythropoiesis and erythrocyte homeostasis. We evaluated the relationship between serum Se levels and the response to ESAs in hemodialysis patients. Methods: In this cross-sectional study, we determined serum Se levels in 173 hemodialysis patients. We analyzed the association of serum Se with ESA responsiveness, as defined by ESA resistance index. Results: Of the study participants, 50% had lower Se levels than the population-based reference values. We found that serum Se levels were significantly and inversely correlated with erythropoiesis resistance index (ERI) but not transferrin saturation (TSAT) or ferritin levels. Multiple regression analyses confirmed the association between Se levels and ESA hyporesponsiveness, independently of other known factors, such as iron status, being female, and dialysis vintage (ß = -0.11, P < 0.001). When patients were divided according to Se levels and iron status, both low serum Se (<10.5 µg/dl) and iron deficiency significantly affected the response to ESA. Conversely, serum Se levels were significantly different among groups when patients were divided according to ERI quartiles. The association of low serum Se with ESA hyporesponsiveness persisted after adjustment of confounding variables. Conclusion: Serum Se levels are associated with the response to ESAs and can predict ESA resistance independently of iron status in Japanese hemodialysis patients. These data open the possibility to test whether Se supplementation reduces ESA demand.

Early clinical signs and treatment of Menkes disease.

Menkes disease (MD) is an X-linked recessive disorder caused by mutations in ATP7A. Patients with MD exhibit severe neurological and connective tissue disorders due to copper deficiency and typically die before 3 years of age. Early treatment with copper injections during the neonatal period, before the occurrence of neurological symptoms, can alleviate neurological disturbances to some degree. We investigated whether early symptoms can help in the early diagnosis of MD. Abnormal hair growth, prolonged jaundice, and feeding difficulties were observed during the neonatal period in 20 of 69, 16 of 67, and 3 of 18 patients, respectively. Only three patients visited a physician during the neonatal period; MD diagnosis was not made at that point. The mean age at diagnosis was 8.7 months. Seven patients, who were diagnosed in the prenatal stage or soon after birth, as they had a family history of MD, received early treatment. No diagnosis was made based on early symptoms, highlighting the difficulty in diagnosing MD based on symptoms observed during the neonatal period. Patients who received early treatment lived longer than their elderly relatives with MD. Three patients could walk and did not have seizures. Therefore, effective newborn screening for MD should be prioritized.

[Perspective on transition from pediatric to adult health care for patients with neurological disease: current situation and issues].

An improvement in efficacy treatment and development of the social support system has led to many patients with neurological disease being able to reach adulthood. Therefore health care for life from pediatrics to adulthood has become necessary. The Special Committee for Measures Against Transition from Pediatric to Adult Health Care of the Japanese Society of Neurology officially started to examine the current situation and issues of transition from pediatric to adult health care in July 2020. Pediatric neurologists and adult neurologists have an awareness of this issue of constructing a better transition from pediatric to adult health care. However, there are some tasks that need to be resolved in the medical system. We intend to improve the understanding of transition and assessment of medical service fees for transition in cooperation with the Japanese Society of Neurology and the Japanese Society of Child Neurology.

Fluctuation of R2* values in blood oxygenation level-dependent MRI during acute and remission phases of IgA vasculitis with nephritis in children.

PURPOSE: Noninvasive assessment of the kidney using blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) has progressed remarkably; indications have expanded to include the evaluation of glomerulonephritis. However, no longitudinal measurements from acute to post-treatment remission phases have been reported. Hence, this study aimed to investigate spin relaxation rate (R2*) values during acute and remission phases in children with glomerulonephritis. MATERIALS AND METHODS: All pediatric patients with IgA vasculitis with nephritis (IgAVN) diagnosed between January 2014 and October 2021 and requiring renal biopsy were retrospectively reviewed; four patients who were observed from onset to remission were included in this study. In total, eight MRIs were performed in the acute and remission phases, and R2* values and fluctuations induced by low-dose oxygen administration were determined from 10 echoes using a 1.5 T MRI system with 4.76-47.6 ms echo times and a 153 ms repetition time. RESULTS: The median age of patients undergoing MRI was 8.5 years in the acute phase and 13.9 years in the remission phase. R2* values of the acute phase were higher than those of the remission phase; however, the difference was not significant (cortex; p = 0.32 and medulla; p = 0.052). Oxygen administration did not cause fluctuations in the R2* values in the cortex or medulla during the acute phase (cortex; p = 0.67 and medulla; p = 0.76); however, in the remission phase, the R2* values in the cortex and medulla significantly decreased due to low-dose oxygen administration (cortex; p < 0.01 and medulla; p < 0.01). CONCLUSION: The fluctuation in R2* values observed during different phases of IgAVN indicates that BOLD MRI may be used to assess disease activity. Therefore, we propose BOLD MRI with low-dose oxygen administration as a noninvasive method to evaluate the activity of glomerulonephritis.

Cyclosporine A C1.5 monitoring reflects the area under the curve in children with nephrotic syndrome: a single-center experience.

BACKGROUND: The currently used single-monitoring method for drug-blood-level evaluation in cyclosporine A (CsA) treatment for nephrotic syndrome (NS) was established through hourly measurements based on adult organ transplantation. However, the pharmacokinetics may differ due to different concomitant medications, age, and conditions. This study was conducted to determine the measurement timing that best reflects the CsA area under the curve (AUC) in pediatric NS. METHODS: This retrospective study included children aged 2-14 years who were started on CsA treatment for idiopathic NS during 2013-2020. AUC0-4 was calculated from 7 points, before and 0.5, 1, 1.5, 2, 3, and 4 h after administration. Mean values at each timing were compared with age-dependent different drug forms. Correlation between AUC0-4 and measurement timing was analyzed. RESULTS: There were 13 patients (11 boys) whose median age during testing was 7.3 years, and the total number of measurements was 94. The highest timing of CsA concentrations was found in C1 59.6%. The content liquid used at younger ages had a faster absorption time to peak value and lower blood concentration than those of capsules. Among the significant correlations observed, AUC0-4 and C1.5 showed the strongest significant correlation coefficient (r = 0.93, P < 0.001). CONCLUSION: In pediatric NS, CsA metabolism may be faster than that in previous organ transplantation. Compared with C2, C1.5 monitoring may result in better disease control as it can best reflect the AUC0-4 and peak values associated with side effects, which are indicators of therapeutic efficacy.

Valine metabolites analysis in ECHS1 deficiency.

Short-chain enoyl-CoA hydratase (ECHS1) is involved in amino acid and fatty acid catabolism in mitochondria and its deficiency causes Leigh syndrome or exercise-induced dystonia. More than 60 patients with this condition have been reported till date. The accumulation of intermediate metabolites of valine is assumed to be responsible for the cytotoxicity. Since protein restriction, including valine reportedly improves neurological symptoms, it is essential to consider the possible incidence of and diagnose ECHS1 syndrome in the earlier stages. This study reported the liquid chromatography with tandem mass spectrometry (LC-MS/MS) urine and plasma metabolite analysis in six cases, including four new cases with ECHS1 deficiency. The values of urine cysteine/cysteamine conjugates from valine metabolites, S-(2-carboxypropyl) cysteine/cysteamine from methacrylyl-CoA, and S-(2-carboxyethyl) cysteine/cysteamine from acryloyl-CoA were separated between six patients and six normal controls. The LC-MS/MS analysis revealed that these metabolites can be used for the early diagnosis and evaluation of diet therapy.

Pharmacokinetics of CuGTSM, a Novel Drug Candidate, in a Mouse Model of Menkes Disease.

PURPOSE: Menkes disease is a rare hereditary disease in which systemic deficiency of copper due to mutation of the ATP7A gene causes severe neurodegenerative disorders. The present parenteral drugs have limited efficacy, so there is a need for an efficacious drug that can be administered orally. This study focused on glyoxal-bis (N(4)-methylthiosemicarbazonato)-copper(II (CuGTSM), which has shown efficacy in macular mice, a murine model of Menkes disease, and examined its pharmacokinetics. In addition, nanosized CuGTSM (nCuGTSM) was prepared, and the effects of nanosizing on CuGTSM pharmacokinetics were investigated. METHODS: CuGTSM or nCuGTSM (10 mg/kg) was administered orally to male macular mice or C3H/HeNCrl mice (control), and plasma was obtained by serial blood sampling. Plasma concentrations of CuGTSM and GTSM were measured by LC-MS/MS and pharmacokinetic parameters were calculated. RESULTS: When CuGTSM was administered orally, CuGTSM and GTSM were both detected in the plasma of both mouse strains. When nCuGTSM was administered, the Cmax was markedly higher, and the mean residence time was longer than when CuGTSM was administered for both CuGTSM and GTSM in both mouse strains. With macular mice, the AUC ratio (GTSM/CuGTSM) was markedly higher and the plasma CuGTSM concentration was lower than with C3H/HeNCrl mice when either CuGTSM or nCuGTSM was administered. CONCLUSION: Absorption of orally administered CuGTSM was confirmed in macular mice, and the nano-formulation improved the absorption and retention of CuGTSM in the body. However, the plasma concentration of CuGTSM was lower in macular mice than in control mice, suggesting easier dissociation of CuGTSM.

Longitudinal Glycaemic Profiles during Remission in 6q24-Related Transient Neonatal Diabetes Mellitus.

INTRODUCTION: Transient neonatal diabetes mellitus (TNDM) is a rare condition that is characterized by the presence of diabetes mellitus during the first 6 months of life and remission by 18 months of age. It usually relapses at a median age of 14 years. Hyperinsulinaemic hypoglycaemia is a relatively common complication during remission. Although ß-cell function is reported to be impaired at relapse, the clinical course of glycaemic profiles during remission in patients with TNDM remains largely unknown. CASE PRESENTATION: Longitudinal glycaemic profiles were investigated annually from remission (185 days) to relapse (14.5 years) in a patient with TNDM due to paternal 6q24 duplication using the oral glucose tolerance test (glucose intake: 1.75 g/kg to a maximum of 75 g). The patient's ß-cell function and insulin sensitivity were assessed by calculating the insulinogenic index, homeostasis model assessment of ß-cell function (HOMA-ß), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index, and Matsuda index. Early insulin response to glucose intake was impaired throughout remission, whereas fasting insulin and ß-cell function by HOMA-ß gradually increased in the first few years since remission, followed by a gradual decline in function. In contrast, HOMA-IR fluctuated and peaked at 6.5 years of age. CONCLUSION: This is the first report of annual longitudinal glycaemic profiles in a patient with 6q24-related TNDM during remission. We identified fluctuations in ß-cell function and insulin resistance during remission.