A rare case of primary coenzyme Q10 deficiency due to COQ9 mutation.

J Pediatr Endocrinol Metab. 2020 Jan 28;33(1):165-170

Authors: Olgac A, Öztoprak Ü, Kasapkara ÇS, Kılıç M, Yüksel D, Derinkuyu EB, Taşçı Yıldız Y, Ceylaner S, Ezgu FS

Abstract
Background Coenzyme Q10 (CoQ10) serves as a shuttle for electrons from complexes I and II to complex III in the respiratory chain, and has important functions within the mitochondria. Primary CoQ10 deficiency is a mitochondrial disorder which has devastating effects, and which may be partially treated with exogenous CoQ10 supplementation. Case presentation A 9-month-old girl patient was referred to our clinic due to growth retardation, microcephaly and seizures. She was the third child of consanguineous parents (first-degree cousins) of Pakistani origin, born at 38 weeks gestation, weighing 2000 g after an uncomplicated pregnancy, and was hospitalized for 3 days due to respiratory distress. She had sustained clonic seizures when she was 4 months old. Physical examination showed microcephaly, truncal hypotonia and dysmorphic features. Metabolic tests were inconclusive. Abdominal ultrasonography revealed cystic appearance of the kidneys. Non-compaction of the left ventricle was detected in echocardiography. Cranial magnetic resonance imaging (MRI) showed hypoplasia of the cerebellar vermis and brain stem, corpus callosum agenesis, and cortical atrophy. A panel testing of 450 genes involved in inborn errors of metabolism (IEM) was performed that showed a novel frameshift c.384delG (Gly129Valfs*17) homozygous mutation in COQ9. A treatment of 5 mg/kg/day exogenous CoQ10 was started when she was 10 months old, and the dosage was increased to 50 mg/kg/day after the exact diagnosis. No objective neurological improvement could be observed after the adjustment of the drug dosage. Conclusions We report a case of CoQ10 deficiency due to a novel COQ9 gene mutation that adds clinical data from a newly diagnosed patient. Our case also outlines the importance of genetic panels used for specific diseases including IEM.

PMID: 31821167 [PubMed - indexed for MEDLINE]

Alternative genomic diagnoses for individuals with a clinical diagnosis of Dubowitz syndrome.

Am J Med Genet A. 2020 Oct 24;:

Authors: Dyment DA, O'Donnell-Luria A, Agrawal PB, Coban Akdemir Z, Aleck KA, Antaki D, Al Sharhan H, Au PB, Aydin H, Beggs AH, Bilguvar K, Boerwinkle E, Brand H, Brownstein CA, Buyske S, Chodirker B, Choi J, Chudley AE, Clericuzio CL, Cox GF, Curry C, de Boer E, de Vries BBA, Dunn K, Dutmer CM, England EM, Fahrner JA, Geckinli BB, Genetti CA, Gezdirici A, Gibson WT, Gleeson JG, Greenberg CR, Hall A, Hamosh A, Hartley T, Jhangiani SN, Karaca E, Kernohan K, Lauzon JL, Lewis MES, Lowry RB, López-Giráldez F, Matise TC, McEvoy-Venneri J, McInnes B, Mhanni A, Garcia Minaur S, Moilanen J, Nguyen A, Nowaczyk MJM, Posey JE, Õunap K, Pehlivan D, Pajusalu S, Penney LS, Poterba T, Prontera P, Doriqui MJR, Sawyer SL, Sobreira N, Stanley V, Torun D, Wargowski D, Witmer PD, Wong I, Xing J, Zaki MS, Zhang Y, Care4Rare Consortium, Centers for Mendelian Genomics, Boycott KM, Bamshad MJ, Nickerson DA, Blue EE, Innes AM

Abstract
Dubowitz syndrome (DubS) is considered a recognizable syndrome characterized by a distinctive facial appearance and deficits in growth and development. There have been over 200 individuals reported with Dubowitz or a "Dubowitz-like" condition, although no single gene has been implicated as responsible for its cause. We have performed exome (ES) or genome sequencing (GS) for 31 individuals clinically diagnosed with DubS. After genome-wide sequencing, rare variant filtering and computational and Mendelian genomic analyses, a presumptive molecular diagnosis was made in 13/27 (48%) families. The molecular diagnoses included biallelic variants in SKIV2L, SLC35C1, BRCA1, NSUN2; de novo variants in ARID1B, ARID1A, CREBBP, POGZ, TAF1, HDAC8, and copy-number variation at1p36.11(ARID1A), 8q22.2(VPS13B), Xp22, and Xq13(HDAC8). Variants of unknown significance in known disease genes, and also in genes of uncertain significance, were observed in 7/27 (26%) additional families. Only one gene, HDAC8, could explain the phenotype in more than one family (N = 2). All but two of the genomic diagnoses were for genes discovered, or for conditions recognized, since the introduction of next-generation sequencing. Overall, the DubS-like clinical phenotype is associated with extensive locus heterogeneity and the molecular diagnoses made are for emerging clinical conditions sharing characteristic features that overlap the DubS phenotype.

PMID: 33098347 [PubMed - as supplied by publisher]

Antineoplastic effect of a novel nanosized curcumin on cutaneous T cell lymphoma.

Oncol Lett. 2020 Dec;20(6):304

Authors: Trochopoulos AGX, Zaharieva MM, Marinova MH, Yoncheva K, Tibi IP, Berger MR, Konstantinov SM

Abstract
Cutaneous T cell lymphomas (CTCLs) are a group of heterogeneous, life-threatening, extra-nodal and lymphoproliferative T cell neoplasms. Since chronic inflammation serves a key role in CTCL progression, curcumin, a natural pigment with proven anti-inflammatory and antineoplastic properties, as well as minimal toxicity, may be used as a therapeutic agent. In the present study, two formulations of curcumin (standard ethanolic and a Pluronic®P-123/F-127 micellar solution) were compared regarding their cytotoxic efficacy and speed of internalization in three CTCL cell lines, namely HuT-78, HH and MJ. In addition, the modulating effect of curcumin on selected proteins involved in the proliferation and progression of the disease was determined. The results indicated the superiority of the Pluronic®P-123/F-127 micellar curcumin over the standard ethanol solution in terms of cellular internalization efficiency as determined by spectrophotometric analysis. Notably, the presence of commonly used media components, such as phenol red, may interfere when interpreting the cytotoxicity of curcumin, due to their overlapping absorbance peaks. Therefore, it was concluded that phenol red-free media are superior over media with phenol red in order to correctly measure the cytotoxic efficacy and cell penetration of curcumin. Depending on the cell line, the IC50 values of micellar curcumin varied from 29.76 to 1.24 µΜ, with HH cells demonstrating the highest sensitivity. This cell line had the lowest expression levels of the Wilms' tumor-1 transcription factor. Performing western blot analyses of treated and untreated CTCL cells, selective signal transduction changes were recorded for the first time, thus making curcumin nano-formulation an attractive and prospective option with therapeutic relevance for CTCL as a rare orphan disease.

PMID: 33093913 [PubMed]

Comparison of International Therapy Guidelines with Regard to the Treatment of Malignant Catatonia.

Pharmacopsychiatry. 2020 Jan;53(1):14-20

Authors: Schönfeldt-Lecuona C, Cronemeyer M, Hiesener L, Connemann BJ, Gahr M, Sartorius A, Mühlbauer V

Abstract
OBJECTIVE: Malignant catatonia (MC) is an extremely rare, life-threatening disorder. It is characterized by catatonic symptoms accompanied by autonomic instability, hyperthermia, and changes in laboratory values. In many cases, MC is not recognized as such. Evidence-based guidelines are essential to ensure quality of treatment, but what do current national and international guidelines recommend?
METHOD: Online search for international guidelines from English-, French-, Italian-, and German-speaking countries whose medical care meets high standards addressing the treatment of MC. These were analyzed and compared regarding statements on MC, recommendations, and strength of scientific evidence.
RESULTS: Fifteen of the identified guidelines were included. Only 5 of 15 comment on the treatment of MC. As for other rare diseases, no detailed recommendations are available. Suggested therapies are limited to benzodiazepines and electroconvulsive therapy. Levels of evidence and grades of recommendation are predominantly low.
CONCLUSION: Many international guidelines do not mention MC. It is not possible to derive a clear algorithm for the treatment of MC from most current guidelines. A thorough update of most guidelines appears to be necessary. Lack of awareness and knowledge of MC among physicians and medical professionals might lead to inadequate or delayed care, worsened outcome, or death.

PMID: 31559622 [PubMed - indexed for MEDLINE]

Diagnosis of Fraser syndrome missed out until the age of six months old in a low-resource setting: a case report.

BMC Pediatr. 2019 08 22;19(1):292

Authors: Mbonda A, Endomba FT, Kanmounye US, Nkeck JR, Tochie JN

Abstract
BACKGROUND: Fraser syndrome is a rare genetic disorder that often presents with ocular, renal, genital and limb's congenital anomalies. The prognosis of this genetic disorder depends on the severity of the combination of congenital malformations, some of which may be fatal. The diagnosis of Fraser syndrome is based on established clinical criteria and genetic tests. The criteria enabling clinical diagnosis are visible dysmorphic features present at birth, hence, Fraser syndrome can easily diagnosed at birth, except when health professionals are inexperienced in clinical recognition. Herein, we report a case of Fraser syndrome missed out at birth and fortuitously diagnosed at the age of six months in a bid to raise clinicians' awareness, particularly in resource-limited settings.
CASE PRESENTATION: We report a case of a six-month-old Cameroonian female infant, born at home and taken the following day to a primary healthcare facility for neonatal care. Her mother had no antenatal care until birth. She presented at our health center with respiratory distress and fever. She had a temperature of 38.8 °C and signs of left lung basal consolidation, suggestive of a left lower lober pneumonia, confirmed on chest x-ray. Other incidental clinical findings were several dysmorphic features like bilateral cryptophthalmos, nasal malformation, anal imperforation (with a perianal fistula), an external genital anomaly and syndactyly characteristic of Fraser syndrome associated with pneumonia. The patient responded well to intravenous antibiotics for the treatment of her pneumonia. Thereafter, she was referred to a pediatric surgeaon for surgical corrections of her bilateral cryptophthalmos, anal imperforation, external genital defect and syndactyly.
CONCLUSION: Here we presented a case of Fraser syndrome in a Cameroonian infant whose diagnosis was missed out at birth and fortuitously made at six months of age. In view of the serious and potentially fatal complications of this genetic disorder, we draw clinicians' attention, especially obstetricians, midwives and pediatricians for a high index of clinical suspicion geared at a timely diagnosis and management. Also, for a timely diagnosis, health education on regular antenatal and postnatal follow ups of  the mother-infant couple respectively, cannot be overemphasized.

PMID: 31438902 [PubMed - indexed for MEDLINE]

Relocation of study participants for rare and ultra-rare disease trials: Ethics and operations.

Contemp Clin Trials. 2019 09;84:105812

Authors: Gelinas L, Crawford B, Kelman A, Bierer BE

Abstract
Clinical trials for investigational new products to treat rare and ultra-rare diseases typically involve a limited number of research sites recruiting from a small pool of patients dispersed over a large geographical area. When remote access is not possible and participants must be present at a trial site, participation in research may require individuals and their families/caregivers to travel great distances, often at significant cost personally and financially and, frequently, for the duration of the trial. This article addresses the ethical and practical issues associated with the practice of sponsors offering financial and other assistance for relocation to trial sites from significant geographical distances, providing both foundational analysis of the ethical issues as well as actionable policy-level guidance on how to best approach these situations.

PMID: 31330189 [PubMed - indexed for MEDLINE]

Yellow Nail Syndrome: A Rare Cause of Pleural Effusion.

Arch Bronconeumol. 2019 11;55(11):589

Authors: De Giacomi F, Srivali N

PMID: 30606631 [PubMed - indexed for MEDLINE]

A rare etiology of preseptal cellulitis: Leishmaniasis.

J Fr Ophtalmol. 2020 Sep;43(7):e247-e249

Authors: Turkoglu EB, Basol I, Ayaz Y, Dogan ME, Apaydın KC, Unal B

PMID: 32499106 [PubMed - indexed for MEDLINE]

A surgical case of primary perivascular epithelioid cell tumor of the heart.

J Card Surg. 2020 Jul;35(7):1732-1735

Authors: Daimon M, Kanki S, Ozawa H, Katsumata T

Abstract
BACKGROUND: We encountered an extremely rare case of perivascular epithelioid cell tumor (PEComa) of the heart.
CASE REPORT: A 54-year-old woman was admitted to our hospital because a solid mass developing in the left atrioventricular groove by computed tomography scans of the chest. Histologic examination of the resected tumor revealed that the tumor had proliferating fusiform or spheroid cells with clear cytoplasm. Immunostaining showed positive results for α-smooth muscle actin, a myogenic marker, and human melanin black-45 (HMB-45), leading to a diagnosis of PEComa. The patient was discharged uneventfully, and there was no recurrence for the last thirteen years postoperatively.
CONCLUSIONS: We experienced a surgical case of PEComa primarily occurring in the heart. Although no sign of a recurrence is observed to date, we consider it necessary to follow up the case carefully.

PMID: 32484981 [PubMed - indexed for MEDLINE]

Adults forms of scimitar syndrome.

J Card Surg. 2020 Jul;35(7):1697-1699

Authors: Mounir R, Nya F, Mohammed B, Ayad A, Bamous M

Abstract
Scimitar syndrome is a rare malformation defined as the partial or total anomalous pulmonary venous return of the right lung veins to the inferior vena cava just above or below the diaphragm. Severe forms of the disease are diagnosed in infancy and childhood. However, because of the mild form of the syndrome in adult patients, they remain asymptomatic and few cases are reported in the literature. We report two adults cases of this syndrome with one presenting with chest discomfort.

PMID: 32445203 [PubMed - indexed for MEDLINE]

A rare childhood case of Behcet's disease and chronic thromboembolic pulmonary hypertension.

J Card Surg. 2020 Jul;35(7):1669-1672

Authors: Wang AS, Rosenzweig EB, Takeda K

Abstract
BACKGROUND: Pulmonary embolism and chronic thromboembolic pulmonary hypertension (CTEPH) are rare complications of Behcet's disease, especially in pediatric patients.
AIMS/METHODS/RESULTS/CONCLUSIONS: This case report highlights a presentation of CTEPH in an adolescent with Behcet's disease. A multidisciplinary approach was required for managing this patient's CTEPH, which successfully reversed the patient's pulmonary hypertension.

PMID: 32419255 [PubMed - indexed for MEDLINE]

Ruptured sinus of valsalva presenting late following repair of tetralogy of fallot.

J Card Surg. 2020 Jul;35(7):1690-1693

Authors: Talwar S, George N, Kothari SS, Sharma A, Goondla K, Choudhary SK

Abstract
Rupture of sinus of valsalva following repair of tetralogy of fallot (TOF) is very rare. It should be suspected as a cause of recurrent or prolonged pleural effusion and congestive cardiac failure in patients who have undergone repair of TOF. We report one such patient.

PMID: 32419207 [PubMed - indexed for MEDLINE]

Etiology and Outcome of non-immune Hydrops Fetalis in Southern China: report of 1004 cases.

Sci Rep. 2019 07 24;9(1):10726

Authors: Meng D, Li Q, Hu X, Wang L, Tan S, Su J, Zhang Y, Sun W, Chen B, He S, Lin F, Xie B, Chen S, Agrawal PB, Luo S, Fu C

Abstract
Non-immune hydrops fetalis (NIHF) is a complex condition with a high mortality and morbidity rate. Here we report the etiology and outcome of 1004 fetuses with NIHF, in a large single Maternal and Children's hospital of Southern China, since the year of 2009 to 2016. Among these 1004 fetuses with NIHF, the etiology was identified prenatally in 722 of them (72%). The most common ones were hematologic diseases and chromosomal abnormalities. There were eight spontaneous abortions, 18 intrauterine fetal demise, 672 pregnancy terminations and 87 were lost to follow-up. 219 of the 1004 fetuses were live-born and the overall survival rate was 21.8% at this point. After birth 16 perinatal or early neonatal deaths were encountered and five lost to follow-up. Of the remaining 198 newborns, 153 thrived without apparent morbidity. The most significant factors associated with mortality were prematurity and low birthweight. In conclusion, we described the largest report of underlying causes and outcome of NIHF in Southern China. Etiologies were identified for 72% of 1004 fetuses with NIHF. And two poor prognostic factors for survival are preterm birth at less than 36.5 weeks and birthweight lower than 2575 g respectively.

PMID: 31341179 [PubMed - indexed for MEDLINE]

29 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 2020/10/21

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.

30 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 2020/10/21

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.

19 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 2020/10/19

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.

6 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 2020/10/14

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.

Adherence to the EAU Guideline Recommendations for Local Tumor Treatment in Penile Cancer: Results of the European PROspective Penile Cancer Study Group Survey (E-PROPS).

Adv Ther. 2020 Oct 10;:

Authors: Pallauf M, Hempel MC, Hupe MC, May M, Haccius M, Weckermann D, Lebentrau S, Hoschke B, Necknig U, Pfitzenmaier J, Manka L, Nuhn P, Törzsök P, Lusuardi L, Merseburger AS

Abstract
INTRODUCTION: Penile cancer (PeCa) is an orphan disease in European countries. The current guidelines are predominantly based on retrospective studies with a low level of evidence. In our study, we aimed to identify predictors for guideline-conform treatment and hypothesize that reference centers for PeCa and physicians' experience promote guideline compliance and therefore correct local tumor therapy.
METHODS: This study is part of the European PROspective Penile Cancer Study (E-PROPS), an international collaboration group evaluating therapeutic management for PeCa in Central Europe. For this module, a 14-item-survey was developed and sent to 681 urologists in 45 European centers. Three questions focused on therapeutic decisions for PeCa in clinical stage Tis, Ta-T1a, and T1b. Four questions addressed potential personal confounders. Survey results were analyzed by bootstrap-adjusted stepwise multivariate linear regression analysis to identify predictors for EAU guideline-conform local treatment of PeCa.
RESULTS: For local therapy of cTis 80.4% recommended guideline-conform treatment, for cTa-cT1a 87.3% and for cT1b 59.1%. In total, 42.4% chose a correct approach in all tumor stages. The number of PeCa patients treated at the hospital, a higher level of training of the physicians, resource-based answering and the option of penile-sparing surgery offered at the hospital matched with giving guideline-conform recommendations and thus accurate local tumor treatment.
CONCLUSION: Patients with PeCa are best treated by experienced physicians, in centers with a high number of cases, which also offer a wide range of local tumor therapy. This could be offered in reference centers.

PMID: 33038006 [PubMed - as supplied by publisher]

Selenoprotein N-related myopathy: a retrospective natural history study to guide clinical trials.

Ann Clin Transl Neurol. 2020 Oct 10;:

Authors: Silwal A, Sarkozy A, Scoto M, Ridout D, Schmidt A, Laverty A, Henriques M, D'Argenzio L, Main M, Mein R, Manzur AY, Abel F, Al-Ghamdi F, Genetti CA, Ardicli D, Haliloglu G, Topaloglu H, Beggs AH, Muntoni F

Abstract
OBJECTIVE: To describe clinical features and disease progression of Selenoprotein N-related myopathy in a large multicenter cohort of patients.
METHODS: Cross-sectional multicenter data analysis of 60 patients (53 families) with Selenoprotein N-related myopathy and single-center retrospective longitudinal analysis of 25 patients (21 families) over a median period of 5.3 years.
RESULTS: The majority of patients (46/60, 77%) presented before age 2 years with hypotonia, poor head/neck control, and developmental delay. At last assessment (median age 14 years; range 2.5 to 36 years), 10/60 patients had minimal or no ambulation. Ventilatory support was initiated in 50/60 patients at a mean Forced Vital Capacity (FVC) of 38% and at a median age of 13 years. Forty-five/60 patients developed scoliosis (at median age 12.1 years) and 18 had scoliosis surgery at a median age of 13.6 years. Five children needed nasogastric feeds and/or gastrostomy. Longitudinal data analysis on 25 patients showed progressive decline of Hammersmith functional motor scores (estimated annual change -0.55 point), time to walk 10 meter, time standing from sitting, and from lying. Sixteen patients had weights < 2nd centile. The estimated change in FVC % per year was -2.04, with a 95% CI (-2.94, -1.14).
CONCLUSIONS: This comprehensive analysis of patients with Selenoprotein N-related myopathy further describes the clinical course of this rare condition. The observed functional motor and respiratory data provide evidence of the slow decline patients experience over time which is useful when considering therapeutic intervention.

PMID: 33037864 [PubMed - as supplied by publisher]

Exome sequencing identifies novel missense and deletion variants in RTN4IP1 associated with optic atrophy, global developmental delay, epilepsy, ataxia, and choreoathetosis.

Am J Med Genet A. 2020 Oct 09;:

Authors: D'Gama AM, England E, Madden JA, Shi J, Chao KR, Wojcik MH, Torres AR, Tan WH, Berry GT, Prabhu SP, Agrawal PB

Abstract
Inherited optic neuropathies (IONs) are neurodegenerative disorders characterized by optic atrophy with or without extraocular manifestations. Optic atrophy-10 (OPA10) is an autosomal recessive ION recently reported to be caused by mutations in RTN4IP1, which encodes reticulon 4 interacting protein 1 (RTN4IP1), a mitochondrial ubiquinol oxydo-reductase. Here we report novel compound heterozygous mutations in RTN4IP1 in a male proband with developmental delay, epilepsy, optic atrophy, ataxia, and choreoathetosis. Workup was notable for transiently elevated lactate and lactate-to-pyruvate ratio, brain magnetic resonance imaging with optic atrophy and T2 signal abnormalities, and a nondiagnostic initial genetic workup, including chromosomal microarray and mitochondrial panel testing. Exome sequencing identified a paternally inherited missense variant (c.263T>G, p.Val88Gly) predicted to be deleterious and a maternally inherited deletion encompassing RTN4IP1. To our knowledge, this is the first report of a non-single nucleotide pathogenic variant associated with OPA10. This case highlights the expanding phenotypic spectrum of OPA10, the association between "syndromic" cases and severe RTN4IP1 mutations, and the importance of nonbiased genetic testing, such as ES, to analyze multiple genes and variants types, in patients suspected of having genetic disease.

PMID: 33037779 [PubMed - as supplied by publisher]