Rare case of chorea-hyperglycaemia-basal ganglia (C-H-BG) syndrome.

BMJ Case Rep. 2018 Apr 17;2018:

Authors: Ahmad S, Mohan Babu P, Shenbagaraj L, George L

Abstract
An 83-year-old woman presented with acute-onset haemichorea and haemiballism particularly affecting the left side of the body. She was known to have type 2 diabetes, which was poorly controlled with sitagliptin. She was hyperglycaemic but not ketotic or acidotic. After she was started on insulin and good glycaemic control was achieved, her abnormal movements dramatically improved. MRI of the brain showed a T1-weighted hyperintense lesion on the right basal ganglia, which is typical of chorea-hyperglycaemia-basal ganglia syndrome. Other causes of chorea, for example, Huntington's disease, Sydenham chorea, Wilson's disease, malignancy, systemic lupus erythematosus, haemorrhage/infarction, thyroid dysfunction, drug-induced chorea and antiphospholipid syndrome, were excluded or deemed less likely given her rapid response to achieving near euglycaemia.

PMID: 29666090 [PubMed - indexed for MEDLINE]

Massive right atrial myxoma presenting as congestive heart failure: an unusual presentation of a rare tumour.

BMJ Case Rep. 2018 Apr 17;2018:

Authors: Agrawal R, Sharma A, Nath RK, Pandit BN

Abstract
Cardiac myxomas are the most common type of primary cardiac tumour. The most common location of cardiac myxoma is left atrium. Right atrial myxomas are very rare and usually asymptomatic or sometimes present with dyspnoea. Right atrial myxoma presenting as a right-sided heart failure is very rare. We report a very rare case of a 52-year-old man of right atrial myxoma presented unsually as right-sided heart failure.

PMID: 29666089 [PubMed - indexed for MEDLINE]

Oral superficial haemosiderotic lymphovascular malformation: a rare presentation.

BMJ Case Rep. 2018 Apr 17;2018:

Authors: Alhassani M, Santhanam V, Basyuni S

Abstract
We present an extremely rare case of a 53-year-old woman with an intraoral superficial haemosiderotic lymphovascular malformation (SHLM), also known as hobnail haemangioma. SHLM is a rare, benign, vascular tumour first described as targetoid haemosiderotic haemangioma, with only a handful of cases reported to present in the oral cavity. The diagnosis was established following complete surgical excision of the lesion, and after 14 months, there are still no signs of recurrence. Although SHLM is an uncommon condition, accurate and timely diagnosis is valuable in distinguishing these lesions from their more serious competing differential diagnoses.

PMID: 29666079 [PubMed - indexed for MEDLINE]

The spectrum of manifestations in desmoplakin gene (DSP) spectrin repeat 6 domain mutations: Immunophenotyping and response to ustekinumab.

J Am Acad Dermatol. 2018 03;78(3):498-505.e2

Authors: Paller AS, Czarnowicki T, Renert-Yuval Y, Holland K, Huynh T, Sadlier M, McAleer MA, Tran G, Geddes GC, Irvine AD, Guttman-Yassky E

Abstract
BACKGROUND: The immune abnormalities underlying the ichthyoses are poorly understood.
OBJECTIVE: To determine the immunophenotype of an ichthyosis resulting from mutations in the spectrin repeat 6 (SR6) domain of desmoplakin gene (DSP) and target therapy on the basis of molecular pathogenesis.
METHODS: Immunophenotyping was performed by using the blood and skin of a girl with SR6 region DSP mutations causing erythroderma/ichthyosis and cardiomyopathy.
RESULTS: On the basis of the discovery of T helper 1 and T helper 17/interleukin 23 skewing in the skin and T helper 17/interleukin 22 skewing in blood, ustekinumab therapy was initiated. Ustekinumab was also administered to a boy with an SR6 region DSP mutation and ichthyosis without cardiomyopathy. Both children responded despite previous poor responses to immunosuppressants and retinoids.
LIMITATIONS: Small number of patients and immunophenotyping in only 1 patient.
CONCLUSION: An understanding of the molecular basis of inflammation in rare cutaneous disorders can lead to targeted therapy, which promises to be more beneficial than broad immunosuppressants.

PMID: 29066275 [PubMed - indexed for MEDLINE]

8 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/10/12

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

8 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/10/12

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

[Rare diseases in post-genomic era.]

Recenti Prog Med. 2017 Jul-Aug;108(7):307-315

Authors: Pulciani S, Vittozzi A, Diemoz S, Nutile E, Taruscio D

Abstract
The Human Genome Project and the "-omics" technologies will in future provide genetic maps and biosynthetic pathways permitting personalized medical interventions directed at maintaining or restoring wellbeing. This is reflected in the strategy aims of 4P medicine in being: predictive, preventive, personalized, and participatory. The results obtained in the field of cystic fibrosis, with the cloning of CFTR gene, and use of Kalydeco®, have demonstrated how using the mentioned strategies could also have success in rare disease management. Kalydeco® is the emblematic example demonstrating the indispensable role of an active patient participation in fully achieving the P4 medicine goals. It is actually the patient involvement that will furnish the fundamental data necessary in defining molecular profiles specific to the health status of any patient. These molecular profiles will contribute in planning preventive, and/or therapeutic interventions aimed at maintaining, and/or restoring the health conditions. Hence, for a correct and effective implementation of P4 medicine, researchers and healthcare professionals should always consider the psychological experiences and characteristics of their patients and families; making them all participants in formulating an appropriate therapeutic path. In achieving this, it will not only be necessary to consider and use concepts of vulnerability and resilience, particularly in the rare disease field, where patient fragility is high, and caregivers are often faced with unique and difficult issues, never confronted before.

PMID: 28845852 [PubMed - indexed for MEDLINE]

Targeting BRAK, MEK, mTOR, and now AKT in histiocytosis: The ongoing revolution of therapies in orphan diseases.

Pediatr Blood Cancer. 2017 05;64(5):

Authors: Haroche J

PMID: 28066975 [PubMed - indexed for MEDLINE]

The galactosemia network (GalNet).

J Inherit Metab Dis. 2017 03;40(2):169-170

Authors: Rubio-Gozalbo ME, Bosch AM, Burlina A, Berry GT, Treacy EP, Steering Committee on behalf of all Galactosemia Network representatives

PMID: 27837294 [PubMed - indexed for MEDLINE]

KCTD7 deficiency defines a distinct neurodegenerative disorder with a conserved autophagy-lysosome defect.

Ann Neurol. 2018 Oct 08;:

Authors: Metz KA, Teng X, Coppens I, Lamb HM, Wagner BE, Rosenfeld JA, Chen X, Zhang Y, Kim HJ, Meadow ME, Wang TS, Haberlandt ED, Anderson GW, Leshinsky-Silver E, Bi W, Markello TC, Pratt M, Makhseed N, Garnica A, Danylchuk NR, Burrow TA, Jayakar P, McKnight D, Agadi S, Gbedawo H, Stanley C, Alber M, Prehl I, Peariso K, Ong MT, Mordekar SR, Parker MJ, Crooks D, Agrawal PB, Berry GT, Loddenkemper T, Yang Y, Maegawa GHB, Aouacheria A, Markle JG, Wohlschlegel JA, Hartman AL, Hardwick JM

Abstract
OBJECTIVE: Several small case series identified KCTD7 mutations in patients with a rare autosomal recessive disorder designated progressive myoclonic epilepsy (EPM3) and neuronal ceroid lipofuscinosis (CLN14). Despite the name KCTD (potassium channel tetramerization domain), KCTD protein family members lack predicted channel domains. We sought to translate insight gained from yeast studies to uncover disease mechanisms associated with deficiencies in KCTD7 of unknown function.
METHODS: Novel KCTD7 variants in new and published patients were assessed for disease causality using genetic analyses, cell-based functional assays of patient fibroblasts and knockout yeast, and electron microscopy of patient samples.
RESULTS: Patients with KCTD7 mutations can exhibit movement disorders or developmental regression before seizure onset, and are distinguished from similar disorders by an earlier age of onset. Although most published KCTD7 patient variants were excluded from a genome sequence database of normal human variations, most newly identified patient variants are present in this database, potentially challenging disease causality. However, genetic analysis and impaired biochemical interactions with cullin 3 support a causal role for patient KCTD7 variants, suggesting deleterious alleles of KCTD7 and other rare disease variants may be underestimated. Both patient-derived fibroblasts and yeast lacking Whi2 with sequence similarity to KCTD7 have impaired autophagy consistent with brain pathology.
INTERPRETATION: Bi-allelic KCTD7 mutations define a neurodegenerative disorder with lipofuscin and lipid droplet accumulation but without defining features of neuronal ceroid lipofuscinosis or lysosomal storage disorders. KCTD7 deficiency appears to cause an underlying autophagy-lysosome defect conserved in yeast, thereby assigning a biological role for KCTD7. This article is protected by copyright. All rights reserved.

PMID: 30295347 [PubMed - as supplied by publisher]

Efficacy and Safety of High-Specific-Activity I-131 MIBG Therapy in Patients with Advanced Pheochromocytoma or Paraganglioma.

J Nucl Med. 2018 Oct 05;:

Authors: Pryma DA, Chin BB, Noto RB, Dillon JS, Perkins S, Solnes L, Kostakoglu L, Serafini AN, Pampaloni MH, Jensen J, Armor T, Lin T, White T, Stambler N, Apfel S, DiPippo V, Mahmood S, Wong V, Jimenez C

Abstract
Patients with metastatic or unresectable (advanced) pheochromocytoma or paraganglioma (PPGL) have poor prognoses and few treatment options. This multicenter, phase 2 trial evaluated the efficacy and safety of high-specific-activity I-131 meta-iodobenzylguanidine (HSA I-131 MIBG) in patients with advanced PPGL. Methods: In this open-label, single-arm study, 81 PPGL patients were screened for enrollment, and 74 received a treatment-planning dose of HSA I-131 MIBG. 68 patients with advanced PPGL received at least one therapeutic dose (~18.5 GBq) of HSA I-131 MIBG intravenously. The primary endpoint was the proportion of patients with at least a 50% reduction in baseline antihypertensive medication use lasting at least 6 months. Secondary endpoints included objective tumor response as assessed by Response Evaluation Criteria in Solid Tumors version 1.0; biochemical tumor marker response; overall survival (OS); and safety. Results: Of the 68 patients who received at least one therapeutic dose of HSA I-131 MIBG, 17 (25%; 95% CI, 16-37%) had a durable reduction in baseline antihypertensive medication use. Among 64 patients with evaluable disease, 59 (92%) had a partial response or stable disease as the best objective response within 12 months. Decreases in elevated (≥1.5 times the upper limit of normal (ULN) at baseline) serum CgA levels were observed with confirmed complete and partial responses 12 months after treatment in 19 of 28 patients (68%). The median OS duration was 36.7 months (95% CI, 29.9-49.1 months). The most common treatment-emergent adverse events were nausea, myelosuppression, and fatigue. No patients had drug-related acute hypertensive events during or after the administration of HSA I-131 MIBG. Conclusion: HSA I-131 MIBG offers multiple benefits, including sustained blood pressure control and tumor response in PPGL patients.

PMID: 30291194 [PubMed - as supplied by publisher]

Drug development for rare cancers in children.

Clin Adv Hematol Oncol. 2017 Jun;15(6):441-443

Authors: Gore L

PMID: 28749903 [PubMed - indexed for MEDLINE]

Anaesthesia and orphan disease: Management of a case of Strumpell-Lorrain disease and review of the literature.

Eur J Anaesthesiol. 2017 08;34(8):562-563

Authors: Ponsonnard S, Damon A, Gueye EM

PMID: 28682816 [PubMed - indexed for MEDLINE]

Anaesthesia and orphan disease series: What is the yield?

Eur J Anaesthesiol. 2017 08;34(8):487-488

Authors: Veyckemans F

PMID: 28682813 [PubMed - indexed for MEDLINE]

Oral lichen sclerosus: a systematic review of reported cases and two new cases.

Int J Dermatol. 2018 May;57(5):521-528

Authors: Kakko T, Salo T, Siponen MK

Abstract
Lichen sclerosus (LS) is a chronic inflammatory mucocutaneous disease with uncertain etiology. It occurs as white plaque-like lesions mostly in the anogenital skin. Oral mucosal involvement is extremely rare. This study aims to summarize the features of published oral lichen sclerosus (OLS) and two new cases. A systematic search of the English literature from 1955 to 2016 was performed in MEDLINE, Scopus, and Web of Science, and cross-references were searched manually. Search phrases included "lichen sclerosus," "mouth," "oral," "lip," "palate," "floor of mouth," "tongue," "gingiva," "buccal mucosa," and "mouth diseases." Cases with clinical and histopathological confirmation of diagnosis of OLS were included. A total of 41 (39 published and 2 new) histologically confirmed OLS cases were available. The median age of OLS patients was 31 years, and 66% of the patients were female. Most of the OLS lesions were asymptomatic. They were located in the labial mucosa (n = 20), lip (n = 15), buccal mucosa (n = 14), gingiva (n = 12), tongue (n = 12), and palate (n = 7). OLS is rare and typically presents as asymptomatic, white, plaque-like lesions. Malignant transformation of preexisting OLS has not been reported.

PMID: 29313955 [PubMed - indexed for MEDLINE]

Langerhans cell histiocytosis in adults: Advances in pathophysiology and treatment.

Cancer Sci. 2018 Oct 03;:

Authors: Kobayashi M, Tojo A

Abstract
Langerhans cell histiocytosis (LCH) is a rare systemic disorder characterized by the accumulation of CD1a+/Langerin + LCH cells and wide-ranging organ involvement. LCH was formerly referred to as Histiocytosis X, until it was renamed in 1987. LCH ßwas named for its morphological similarity to skin Langerhans cells. Studies have demonstrated that LCH cells originate from myeloid dendritic cells rather than skin Langerhans cells. There has been significant debate regarding whether LCH should be defined as an immune disorder or a neoplasm. A breakthrough in understanding the pathogenesis of LCH occurred in 2010 when a gain-of-function mutation in BRAF (V600E) was identified in more than half of LCH patient samples. Studies have since demonstrated that 100% of LCH cases exhibit ERK phosphorylation, indicating that LCH is likely to be a clonally expanding myeloid neoplasm. LCH is now defined as inflammatory myeloid neoplasms in the revised 2016 Histiocyte Society classification. Randomized trials and novel approaches have led to improved outcomes for pediatric patients, but no well-defined treatments for adult patients have been developed to date. Although LCH is not fatal in all cases, delayed diagnosis or treatment can result in serious impairment of organ function and decreased quality of life. This study summarizes recent advances in the pathophysiology and treatment of adult LCH, to raise awareness of this "orphan disease". This article is protected by copyright. All rights reserved.

PMID: 30281871 [PubMed - as supplied by publisher]

Genetics of personalized medicine: cancer and rare diseases.

Cell Oncol (Dordr). 2018 Jun;41(3):335-341

Authors: Alves ITS, Condinho M, Custódio S, Pereira BF, Fernandes R, Gonçalves V, da Costa PJ, Lacerda R, Marques AR, Martins-Dias P, Nogueira GR, Neves AR, Pinho P, Rodrigues R, Rolo E, Silva J, Travessa A, Leite RP, Sousa A, Romão L

Abstract
The 21st annual meeting of the Portuguese Society of Human Genetics (SPGH), organized by Luísa Romão, Ana Sousa and Rosário Pinto Leite, was held in Caparica, Portugal, from the 16th to the 18th of November 2017. Having entered an era in which personalized medicine is emerging as a paradigm for disease diagnosis, treatment and prevention, the program of this meeting intended to include lectures by leading national and international scientists presenting exceptional findings on the genetics of personalized medicine. Various topics were discussed, including cancer genetics, transcriptome dynamics and novel therapeutics for cancers and rare disorders that are designed to specifically target molecular alterations in individual patients. Several panel discussions were held to emphasize (ethical) issues associated with personalized medicine, including genetic cancer counseling.

PMID: 29633150 [PubMed - indexed for MEDLINE]

13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/10/03

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/10/03

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

8 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/10/02

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.