Rare Disorder Research Articles

Synergistic effects of resveratrol and enzyme replacement therapy in the Mucopolysaccharidosis type I

Mucopolysaccharidosis type I (MPS I) is a rare genetic disorder caused by mutations in the IDUA gene, leading to alpha-L-iduronidase enzyme deficiency and resulting in the accumulation of glycosaminoglycans (GAG; heparan and dermatan sulfate) in lysosomes. The consequent GAG accumulation within cells leads to organ dysfunction and a range of debilitating symptoms. Enzyme replacement therapy (ERT) is the prevailing treatment, but its limitations (including high cost, time requirements, inefficiency in treatment of central nervous system (CNS), and immunogenicity) necessitate exploration of alternative therapeutic strategies. This research propose a novel approach leveraging the synergistic effects of ERT and resveratrol-induced autophagy. Resveratrol, with its immunomodulatory and GAG degradation-stimulating properties, holds a promise in mitigating immune responses triggered by ERT. Moreover, its ability to penetrate the blood–brain barrier presents a potential solution for addressing CNS manifestations. This study employed cells from MPS I patients to investigate the combined effects of resveratrol and the enzyme. Evaluation of the therapeutic impact involved assessing GAG accumulation enzyme testing, and examining lysosome functionality and the autophagy process through fluorescence microscopy and Western blotting. The combined therapy stimulated the lysosomal mannose-6-phosphate receptor (M6PR) and lysosome biogenesis through the transcription factor EB (TFEB). Additionally, initial block of autophagy in autophagosome formation was relieved after the combined therapy and resveratrol alone. Together with increased enzyme activity through stimulation of the receptor, this synergistic therapy can be considered a new potential treatment for MPS I patients, improving their overall quality of life.

A novel variant in the GNE gene in a Malian patient presenting with distal myopathy.

GNE-myopathy (GNE-M) is a rare autosomal recessive disorder caused by variants in the GNE gene. We report a novel variant in GNE causing GNE-M in a Malian family. A 19-year-old male patient from consanguineous marriage was seen for progressive walking difficulty. Neurological examination found predominant distal muscle weakness and atrophy, decreased tendon reflexes, predominating in lower limbs. Electroneuromyography showed an axonal neuropathy pattern. However, whole exome sequencing (WES) revealed a novel biallelic variant in GNE c.1838G > A:p.Gly613Glu, segregating with the phenotype within the family. This study highlights its diagnosis challenges in sub-Saharan Africa and broadens the genetic spectrum of this rare disease.

Defective thyroid hormone transport to the brain leads to astroglial alterations

Allan-Herndon-Dudley syndrome (AHDS) is a rare X-linked disorder that causes severe neurological damage, for which there is no effective treatment. AHDS is due to inactivating mutations in the thyroid hormone transporter MCT8 that impair the entry of thyroid hormones into the brain, resulting in cerebral hypothyroidism. However, the pathophysiology of AHDS is still not fully understood and this is essential to develop therapeutic strategies. Based on evidence suggesting that thyroid hormone deficit leads to alterations in astroglial cells, including gliosis, in this work, we have evaluated astroglial impairments in MCT8 deficiency by means of magnetic resonance imaging, histological, ultrastructural, and immunohistochemical techniques, and by mining available RNA sequencing outputs. Apparent diffusion coefficient (ADC) imaging values obtained from magnetic resonance imaging showed changes indicative of alterations in brain cytoarchitecture in MCT8-deficient patients (n = 11) compared to control subjects (n = 11). Astroglial alterations were confirmed by immunohistochemistry against astroglial markers in autopsy brain samples of an 11-year-old and a 30th gestational week MCT8-deficient subjects in comparison to brain samples from control subjects at similar ages. These findings were validated and further explored in a mouse model of AHDS. Our findings confirm changes in all the astroglial populations of the cerebral cortex in MCT8 deficiency that impact astrocytic metabolic and mitochondrial cellular respiration functions. These impairments arise early in brain development and persist at adult stages, revealing an abnormal distribution, density, morphology of cortical astrocytes, along with altered transcriptome, compatible with an astrogliosis-like phenotype at adult stages. We conclude that astrocytes are potential novel therapeutic targets in AHDS, and we propose ADC imaging as a tool to monitor the progression of neurological impairments and potential effects of treatments in MCT8 deficiency.

Patient-reported outcomes and functional assessments of patients with Alkaptonuria in a 3-year Nitisinone treatment trial

Alkaptonuria is a rare disorder of tyrosine catabolism caused by deficiency of homogentisate 1,2-dioxygenase that leads to accumulation of homogentisic acid (HGA). Deposition of HGA-derived polymers in connective tissue causes progressive arthropathy of the spine and large joints, cardiac valvular disease, and genitourinary stones beginning in the fourth decade of life. Nitisinone, a potent inhibitor of the upstream enzyme, 4-hydroxyphenylpyruvate dioxygenase, dramatically reduces HGA production. As such, nitisinone is a proposed treatment for alkaptonuria. A randomized clinical trial of nitisinone in alkaptonuria confirmed the biochemical efficacy and tolerability of nitisinone for patients with alkaptonuria but the selected primary outcome did not demonstrate significant clinical benefit. Given that alkaptonuria is a rare disease with slow progression and variable presentation, identifying outcome parameters that can detect significant change during a time-limited clinical trial is challenging. To gain insight into patient-perceived improvements in quality of life and corresponding changes in physical function associated with nitisinone use, we conducted a post-hoc per protocol analysis of patient-reported outcomes and a functional assessment. Analysis revealed that nitisinone-treated patients showed significant improvements in complementary domains of the 36-Item Short-Form Survey (SF-36) and 6-min walk test (6MWT). Together, these findings suggest that nitisinone improves both quality of life and function of patients with alkaptonuria. The observed trends support nitisinone as a therapy for alkaptonuria.

The association between lipoprotein(a) levels and ischemic stroke in children: A case-control study.

Pediatric arterial ischemic stroke (AIS) is a rare disorder, associated with severe morbidity. In adults, elevated lipoprotein(a) (Lp(a)), a cholesterol-like particle, is associated with ischemic stroke. However, data on Lp(a) and pediatric AIS are scarce. Therefore, we evaluated the association between Lp(a) levels and pediatric AIS. We included children who suffered an AIS (≤18years) and were treated in a tertiary center in Amsterdam, the Netherlands. Two groups of children with AIS were identified: (i) neonates and (ii) children older than 29days. A case-control study was performed, with the latter group as cases and children without AIS as control group. Cases and controls were matched for age of Lp(a) testing and sex. Multivariable logistic regression models were used. Thirteen neonates and 23 children were included. Mean (SD) age of AIS was 0.6 (2.0) days and 9.2 (6.3) years, respectively. Children with AIS were matched to 62 controls. Lp(a) levels of greater than 50mg/dL were more prevalent in children with AIS compared to controls (21.7% vs. 3.2%, p=.02). A significant association was found between Lp(a) and AIS (odds ratio [OR] adjusted for age at Lp(a) testing, body mass index [BMI], measurement assay: 1.36 per 10mg/dL increase of Lp(a), 95% confidence interval [CI]: 1.02-1.82, p=.041). In this study, Lp(a) levels were positively associated with the risk of AIS in children, suggesting that high Lp(a) might be an independent risk factor for AIS. This underlines the importance of Lp(a) measurement in children with AIS.

Pediatric TAFRO syndrome: A multi-institution case series illustrating clinical challenges and excellent outcomes.

A rare lymphoproliferative disorder involving thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), renal dysfunction (R), and organomegaly (O), called TAFRO syndrome, was first reported in 2010. Considered a variant of idiopathic multicentric Castleman's disease, the recent discovery and rarity of this syndrome pose challenges to diagnosis and management. Herein, we review three pediatric cases, including an infant, that illustrate the heterogeneity of TAFRO syndrome. Despite differences in presentation and treatment responses, all patients experienced excellent outcomes. This multi-institutional case series highlights the need to work toward earlier diagnosis and improved long-term management recommendations for patients with TAFRO syndrome.

IgG4-related disease with subcutaneous involvement and the associated diagnostic challenges with MRI.

IgG4-related disease is a rare fibroinflammatory disorder characterized by the infiltration of IgG4-rich plasma cells. Herein, we report a case of IgG4-related disease of the subcutaneous tissue with atypical MRI findings and difficulties in the histopathological examination using needle biopsy. Based on the clinical presentation and MRI findings, the patient was diagnosed with a benign myxoid or cystic tumor. Additionally, histopathological findings from a needle biopsy suggested a myxoma. Therefore, the correct diagnosis of IgG4-related disease was not made preoperatively. The resected specimens confirmed IgG4-related disease with an IgG4/IgG ratio > 80%. Previous reports have shown that the MRI findings of IgG4-related disease mimic both malignancy and inflammation; surprisingly, the features of subcutaneous IgG-related disease, including tail sign, unclear border, and heterogeneous enhancement, were similar to those found in sarcoma. Therefore, histopathological findings are needed for a correct diagnosis. Furthermore, careful examination is essential because the neoplasm and inflammation may overlap with IgG4-related disease, and needle biopsy is not fully reflective of the tumor. As is highlighted in the present case, IgG4-related disease is often misdiagnosed; therefore, clinicians should adequately recognize that even if the histopathological findings in biopsy were consistent with those observed in the MRI, misdiagnosis may occur.

Plasma cell-directed therapies induce profound clinical and durable responses in patients with severe or relapsed/refractory scleromyxedema.

Scleromyxedema (SM) is a rare skin disorder related to monoclonal gammopathy. High dose intravenous immunoglobulins (HDIVIg) are usually used as a frontline therapy with initial efficacy. However, some patients evolve with relapse, refractory state or severe extra-cutaneous complications such as dermato-neuro syndrome (DNS) or cardiac involvement. The objective of the study is to evaluate the use of anti-plasma cell treatment in these patients in order to obtain a deep and durable dermatological and haematological response. We report here eight patients treated with HDIVIg together with anti-plasma cell therapy including: lenalidomide and dexamethasone (n = 5); bortezomib, cyclophosphamide and dexamethasone (n = 1); daratumumab, lenalidomide and dexamethasone (n = 2). Combination of HDIVIg with a treatment targeting the monoclonal component led to a high level of haematological remission and drastically improved skin response with an acceptable safety profile in all patients. Moreover, HDIVIg was reduced and stopped in 4 of the 7 patients who achieved complete remission. The association of lenalidomide and dexamethasone with HDIVIg could improve the treatment of relapsed or severe SM.

Post-surgical complications of supernumerary teeth in the mandibular premolar area: A systematic review

In the mandibular premolar area, supernumerary teeth are a rare disorder that are rarely documented in the literature. The purpose of this study was to evaluate the post-surgical problems associated with the buccal and lingual techniques used to treat the extra teeth in this area. Using PubMed, PubMed Central, Science Direct, Cochrane, Wiley, and manual search, a thorough search was done to locate and identify cases and case series with extra teeth in the mandibular premolar region. For every study that was included, data on the surgical technique and postoperative problems were documented. Seven studies involving 90 patients were included. Supernumerary teeth in the mandibular premolar region were predominantly found in male patients (65.55 %), with most cases occurring in the right mandibular region (77.16 %). Postoperative complications after removing supernumerary teeth using buccal and lingual approaches were similar, with only one complication reported among the 90 cases reviewed. Although the findings suggest that surgical management of supernumerary teeth in the mandibular premolar region is relatively safe, caution is advised due to the limited sample size. Detailed pre-operative evaluation, a comprehensive treatment plan, and regular follow-up can minimize postoperative complications.

Brain MRI findings in paediatric genetic disorders associated with white matter abnormalities.

To describe the specific brain magnetic resonance imaging (MRI) patterns of the paediatric genetic disorders associated with white matter abnormalities in Northern Finland. In this retrospective population-based longitudinal study, brain MRI scans accumulated from 1990 to 2019 at Oulu University Hospital, Finland, were assessed. Inclusion criteria were defined as leukodystrophies or genetic diseases with significant white matter abnormalities that did not meet the criteria for leukodystrophy, at least one brain MRI, and age under 18 years at diagnosis. A total of 83 patients (48 males, 35 females) were found with 52 different diseases. The median age at the time of the brain MRI was 22 months (interquartile range [IQR] = 46 months). In 72 (87%) of the children, brain MRIs revealed abnormal findings, including cerebral white matter abnormalities (n = 49, 59%), brainstem signal abnormalities (n = 28, 34%), thinning of the corpus callosum (n = 30, 36%), delayed myelination (n = 11, 13%), and permanent hypomyelination (n = 9, 11%). Symmetrical and bilateral white matter signal patterns of the brain MRI should raise suspicion of genetic disorders when the clinical symptoms are compatible. This study illustrates brain imaging patterns of childhood-onset genetic disorders in a population in Northern Finland and improves the diagnostic accuracy of rare genetic disorders.

Alternative Venous Pathways: A Potential Key Imaging Feature for Early Diagnosis of Sturge-Weber Syndrome Type 1.

Sturge-Weber syndrome is a rare congenital disorder characterized by cortical atrophy and calcifications on late-stage imaging. Understanding the evolution of brain lesions is crucial for effective early interventions, yet the timeline remains unclear. We aimed to evaluate early brain MRI findings and their progression longitudinally on follow up MRI in children diagnosed with Sturge-Weber syndrome. We retrospectively included all children with a confirmed diagnosis of Sturge-Weber syndrome between 2009 and 2023 that had at least 2 available MRIs performed before the age of 2 years. A pediatric radiologist and a pediatric neuroradiologist evaluated all the MRI scans for pial enhancement, choroid plexus enlargement, atrophy, calcifications, a prominent subarachnoid varicose network, trans medullary veins, subependymal veins, and deep extra ventricular veins. Descriptive analysis was used for demographic data and brain lesion prevalence. Cumulative incidence curves were used to show the timeline of emerging lesions. K-means clustering was used to categorize the lesions based on their prevalence at 1, 2, 3, 6, 12, 18, and 24 months after birth. Nine patients met the inclusion criteria. Median ages at the first and last MRIs were 35 days (IQR: 11-123) and 294 days (IQR: 208-465), respectively. The most prevalent lesions at the first MRI were subarachnoid varicose network (88.9%) and trans medullary veins (77.8%), while prevalence of atrophy and calcifications differed most between the first and last MRIs. The results of the elbow method and K-means clustering showed that we can divide Sturge-Weber syndrome lesions into 3 groups based on their timeline of emergence. The first cluster contained subarachnoid varicose network, trans medullary veins, subependymal veins, and choroid plexus enlargement. The second cluster contained deep extra ventricular veins, pial enhancement, accelerated myelination, and atrophy. The last cluster contained calcifications. Our findings suggest that dilated venous channels emerge early as a compensatory mechanism, preceding atrophy and calcification. Additionally, these dilated channels precede the appearance of abnormal contrast enhancement of the pia, often termed leptomeningeal angioma. This underscores the importance of early recognition and monitoring of these initial imaging indicators in clinical practice. ASL = Arterial Spin Labelled; MinIP = Minimum intensity projection; SWS = Sturge-Weber Syndrome.

Adult-onset chronic recurrent multifocal osteomyelitis: A case report of a rare entity

Background: Chronic recurrent multifocal osteomyelitis is a rare autoimmune disorder causing inflammatory joint lesions. It has an estimated prevalence of 1-2 per million while adult-onset disease constitutes only 6.3% of patients. Case report: We present a case of a 44 years old male who presented to the rheumatology clinic with lower back pain for twelve years. Magnetic resonance imaging of the lumbosacral spine showed ovoid areas of abnormal signal intensities along superior and inferior endplates of multiple vertebrae of the dorsolumbar and sacral spine. Computed tomography guided biopsy of L4 vertebrae was done. Histopathology revealed linear cores of degenerating fibrocartilage focally exhibiting small spicules of mineralized bone and fibro-collagenous tissue. He initially did not respond to traditional therapy. His symptoms improved with the addition of a Janus Kinase inhibitor. To the best of our knowledge, this is the first case of chronic recurrent multifocal osteomyelitis to be reported from Pakistan. doi: https://doi.org/10.12669/pjms.40.8.8765 How to cite this: Jibril H, Riaz M, Ali SA. Adult-onset chronic recurrent multifocal osteomyelitis: A case report of a rare entity. Pak J Med Sci. 2024;40(8):---------. doi: https://doi.org/10.12669/pjms.40.8.8765 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Long-term cardiovascular outcomes and mortality with enzyme replacement therapy in patients with mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (MPS II) is a rare multisystemic lysosomal disorder in which cardiac issues can lead to serious dysfunction and an increased risk of fatal cardiac failure. However, studies on major adverse cardiac event (MACE) outcomes in MPS II are lacking. This study evaluated the cardiovascular outcomes and impact of enzyme replacement therapy (ERT) in patients with MPS II in South Korea. In this national cohort study, utilizing data from the National Health Insurance Database, we evaluated 127 patients with MPS II over a 14-year period to investigate the effects of ERT on MACE and all-cause mortality. We tracked MACE incidence, defined by hospitalizations for cardiovascular events, from diagnosis and adjusted the hazard ratios for MACE using Cox modeling. Over an average follow-up period of 7.3 years, we identified 16 cases of MACE among patients (17.35 per 1000 person-years; 95% confidence interval, 10.74-26.83). Patients receiving ERT exhibited a significantly lower incidence of MACE than untreated patients, with cumulative incidences showing a marked difference of 8.3 years. Notably, initiating ERT at earlier stages post-diagnosis was associated with improved outcomes, underscoring the importance of timely treatment. The key risk factors for MACE included specific arrhythmias, a history of invasive procedures, and depression. Early ERT significantly reduced MACE risk and increased survival in patients with MPS II. This underscores the importance of prompt treatment initiation and comprehensive care to address key risk factors and advocates for an expanded therapeutic strategy to enhance MPS II outcomes.

Missense variants in CMS22 patients reveal that PREPL has both enzymatic and non-enzymatic functions.

Congenital myasthenic syndrome-22 (CMS22, OMIM 616224) is a rare genetic disorder caused by deleterious genetic variation in the prolyl endopeptidase-like (PREPL) gene. Previous reports have described patients with deletions and nonsense variants in PREPL, but nothing is known about the effect of missense variants in the pathology of CMS22. In this study, we have functionally characterized missense variants in PREPL from three CMS22 patients, all with hallmark phenotypes. Biochemical evaluation revealed that these missense variants do not impair hydrolase activity, thereby challenging the conventional diagnostic criteria and disease mechanism. Structural analysis showed that the variants affect regions most likely involved in intra-protein or protein-protein interactions. Indeed, binding to a selected group of known interactors was differentially reduced for the three mutants. The importance of non-hydrolytic functions of PREPL was investigated in catalytically inactive PREPL p.Ser559Ala cell lines which showed that hydrolytic activity of PREPL is needed for normal mitochondrial function but not for regulating AP1-mediated transport in the trans-Golgi network. In conclusion, these studies showed that CMS22 can be caused not only by deletion and truncation of PREPL but also by missense variants that do not necessarily result in a loss of hydrolytic activity of PREPL.

A Complete Sojourn of Monoclonal Antibodies: AI, Rare Diseases / Disorders And Immunotoxic Effects

Abstract: Monoclonal antibodies (mAbs) are magic bullets proved to be a wonder in the pharmaceutical as well as medical fields. These are produced by various methods like hybridoma technology, phage display technology, YAC technology, and transgenic animals and plants. Based on the percentage of animal origin, mAbs are divided into chimeric, murine, humanized, and fully human. This review covers the history and methods of mAb production, immunotoxicity (Immunosuppression, immunostimulant, autoimmunity, hypersensitivity) associated with mAbs, and targets of mAbs. It also compiles mAb production using AI, new modifications, and novel mAbs, with its various clinical trial information ensuring the use of mAbs in rare diseases and disorders.

Successful case report of congenital long-segment complex tracheal stenosis treated with sliding tracheoplasty associated with pulmonary artery vascular ring

BackgroundCongenital tracheal stenosis is a rare structural obstructive disorder affecting a segment of the trachea. It is often caused by complete or nearly complete cartilaginous rings narrowing the airway. Approximately 50% of cases are associated with abnormal left pulmonary artery rings.Case presentationWe present the case of a 4-month-old female infant with complex congenital tracheal stenosis associated with a left pulmonary artery vascular ring and congenital heart disease. The patient underwent successful surgical intervention involving repair of the congenital heart defect and reimplantation of the pulmonary artery, followed by sliding tracheoplasty in one surgery procedure. Postoperative outcomes were favorable, with successful extubating and resolution of respiratory symptoms.ConclusionsSliding tracheoplasty proved an effective treatment option in this complex case, highlighting its reproducibility and favorable outcomes in managing congenital tracheal stenosis.

Treacher Collins syndrome: current and emerging treatment options

Treacher Collins syndrome is a rare congenital disorder characterized by bilateral craniofacial malformations, including mandibular and zygomatic hypoplasia, cleft palate, and eye anomalies, resulting in significant variability in symptom severity. The syndrome, with an incidence of approximately 1 in 50,000 births, is primarily caused by mutations in the TCOF1 gene and less frequently by mutations in POLR1C and POLR1D genes, disrupting ribosome biogenesis crucial for craniofacial development. Clinical manifestations encompass diverse craniofacial, auditory, and skeletal abnormalities, often leading to airway complications and hearing loss. Management involves a multidisciplinary approach, combining surgical interventions such as mandibular distraction osteogenesis and orthognathic surgeries with advanced imaging techniques for precise planning. Hearing loss is managed with bone conduction aids and cochlear implants, although outcomes may vary due to associated anomalies. Genetic testing aids in diagnosis and family planning decisions, while emerging therapies like genome editing and regenerative medicine show promise for future treatments. Despite challenges in long-term management and relapse rates in surgical corrections, ongoing research aims to enhance therapeutic efficacy and patient outcomes, emphasizing the need for tailored treatment strategies addressing both functional and aesthetic aspects.

Clinical cases series and pathogenesis of Lamb-Shaffer syndrome in China

BackgroundLamb-Shaffer syndrome (LAMSHF, OMIM: 616803) is a rare neurodevelopmental disorder characterized by global developmental delay, intellectual disability, poor expressive speech, which is attributed to haploinsufficiency by heterozygous variants of SOX5 gene (SRY-Box Transcription Factor 5, HGNC: 11201) on chromosome 12p12. A total of 113 cases have been reported in the world, however, only 3 cases have been reported.in China. Here, we aimed to report novel variants of SOX5 gene and provide examples for clinical diagnosis by reporting the clinical phenotype of a series of Chinese patients with LAMSHF.MethodsThis study retrospectively collected the information of families of LAMSHF patients in China. Whole Exome Sequencing (WES) were performed to confirm the diagnosis of 4 children with unexplained developmental delay or epilepsy. A minigene splicing assay was used to verify whether the splice variant affected splicing. Meanwhile, a literature review was conducted to analyze the clinical and genetic characteristics of patients with LAMSHF.ResultsThree of the LAMSHF patients had a de novo heterozygous mutation in the SOX5 gene respectively, c.290delC (p.Pro97fs*30), chr12:23686019_24048958del, c.1772-1C > A, and the remaining one had a mutation inherited from his father, c.1411C > T (p.Arg471*). The main clinical manifestations of these children were presented with global developmental delays, and one of them also had seizures. And the results of the minigene experiment indicated that the splice variant, c.1772-1C > A, transcribed a novel mRNA product which leaded to the formation of a truncated protein.ConclusionsThrough a comprehensive review and analysis of existing literature and this study showed intellectual disability, speech delay and facial dysmorphisms were common clinical manifestation, while the seizures and EEG abnormalities were rare (21/95, 22.16%). Notably, we represent the largest sample size of LAMSHF in Asia that encompasses previously unreported SOX5 gene mutation, and a minigene testing have been conducted to validate the pathogenicity of the c.1772-1C > A splice variant. The research further expands the phenotype and genotype of LAMSHF while offers novel insights for potential pathogenicity of genes locus.

Assessment of the degree of disability of the Polish NBIA-MPAN population based on a patient survey

Neurodegeneration with brain iron accumulation (NBIA) describes a group of extremely rare hereditary disorders with an estimated prevalence of 1–3/1,000,000. Mitochondrial membrane protein associated neurodegeneration (MPAN) is the third most common form of NBIA, accounting for 10% of NBIA cases globally and up to 50% of cases in Poland. This survey was conducted by the Association NBIA Poland to collect data on the functioning of patients with NBIA/MPAN based on self-reported EQ-5D-5L (EuroQoL 5-Dimension 5-Level) scores. A total of 50 patients living in Poland, including 26 patients with NBIA/MPAN, participated in the study. The mean age of NBIA/MPAN patients was 22 years; the mean age at symptom onset is 10 years. At the time of the survey, most patients were disabled and required assistance with daily activities. More than 50% of participants needed help with hygiene or dressing, and 40% were unable to walk on their own. Nearly 50% of patients declared symptoms indicating lowered mood. The survey showed that NBIA/MPAN leads to significant disability within a short period of time after symptom onset. Intensive work is underway to discover the role of the C19orf12 protein and develop therapeutic strategies. Actions are necessary to improve the comfort of everyday life of patients with NBIA/MPAN and to improve access to rehabilitation, including home-based programmes.

Cutaneous Plasmacytosis Treated with Tocilizumab.

Cutaneous plasmacytosis is a rare disorder of unknown etiology characterized by the proliferation of mature plasma cells in the skin and polyclonal hypergammaglobulinemia. Cutaneous plasmacytosis is associated with an elevated Interleukin-6 level. Anti-IL-6 therapy has not been reported as a therapy for idiopathic cutaneous plasmacytosis. This article presents a case of a Caucasian woman with idiopathic cutaneous plasmacytosis who was successfully treated with tocilizumab, a monoclonal anti-IL-6 receptor antibody. The patient experienced improvement in both her cutaneous lesions as well as subjective symptoms after 2 months on tocilizumab.