De novo variant in KIF26B is associated with pontocerebellar hypoplasia with infantile spinal muscular atrophy.

Am J Med Genet A. 2018 Aug 27;:

Authors: Wojcik MH, Okada K, Prabhu SP, Nowakowski DW, Ramsey K, Balak C, Rangasamy S, Brownstein CA, Schmitz-Abe K, Cohen JS, Fatemi A, Shi J, Grant EP, Narayanan V, Ho HH, Agrawal PB

Abstract
KIF26B is a member of the kinesin superfamily with evolutionarily conserved functions in controlling aspects of embryogenesis, including the development of the nervous system, though its function is incompletely understood. We describe an infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. We performed whole exome sequencing on the trio and identified a de novo KIF26B missense variant, p.Gly546Ser, in the proband. This variant alters a highly conserved amino acid residue that is part of the phosphate-binding loop motif and motor-like domain and is deemed pathogenic by several in silico methods. Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity. Overall, KIF26B may play a critical role in the brain development and, when mutated, cause pontocerebellar hypoplasia with arthrogryposis.

PMID: 30151950 [PubMed - as supplied by publisher]

Esophageal metastasis of stem cell-subtype hepatocholangiocarcinoma: Rare presentation of a rare tumor.

World J Gastroenterol. 2018 Feb 21;24(7):870-875

Authors: Salimon M, Chapelle N, Matysiak-Budnik T, Mosnier JF, Frampas E, Touchefeu Y

Abstract
Hepatocholangiocarcinoma (cHCC-ICC) is a rare primary hepatic tumor defined by the presence of histological features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Its prevalence ranges from 1%-5% of all primary liver cancers. We report the case of a 55-year-old cirrhotic male patient admitted to our university hospital for dysphagia, revealing a 10 cm lower-third esophageal metastasis of an unresectable cHCC-ICC with stem-cell features. Computed tomography and abdominal magnetic resonance imaging scans revealed multiple hepatic lesions combining features of both HCC and ICC, associated with synchronous bone metastasis. Histological and immunohistochemical analyses of biopsies from the esophageal lesion and the hepatic tumor confirmed the diagnosis of cHCC-ICC with a stem cell-subtype, according to the World Health Organization classification. After a multidisciplinary meeting, the patient was treated with chemotherapy. He received two cycles of a gemcitabine plus cisplatin regimen before bone progression, and he died 3 mo after the initial diagnosis.

PMID: 29467557 [PubMed - indexed for MEDLINE]

Ustekinumab treatment of pityriasis rubra pilaris: A report of five cases.

J Dermatol. 2018 Feb;45(2):202-206

Authors: Napolitano M, Lembo L, Fania L, Abeni D, Didona D, Didona B

Abstract
Pityriasis rubra pilaris (PRP) is a rare, chronic, inflammatory skin disease of unknown etiology. Patients refractory to conventional therapies have been treated successfully with biologic drugs such as anti-tumor necrosis factor agents. Recently, a role of the interleukin-23/T-helper 17 axis in PRP has been described. Our objective was to assess the effectiveness of ustekinumab in five patients with adult-onset PRP refractory to conventional therapies. In the present study, four patients had type I and one patient type II adult-onset PRP. They were treated with three s.c. doses of ustekinumab at weeks 0, 4 and 16. Clinical response was evaluated monthly during treatment up to a 15-month follow-up period. All patients promptly showed a decrease in erythema, follicular hyperkeratosis and scaling. After three injections, complete remission of skin lesions was achieved in four out of five cases and a significant clinical improvement was shown in one case. To the best of our knowledge, this is the largest case series reported on ustekinumab treatment in PRP. Our results, in addition to previous studies from other groups, suggest that ustekinumab may be a possible first-line treatment for PRP patients refractory to conventional therapies.

PMID: 29080273 [PubMed - indexed for MEDLINE]

10 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 2018/08/28

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.

10 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 2018/08/28

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.

Renal cell carcinoma in a horseshoe kidney: Report of a rare disease.

Niger Postgrad Med J. 2016 Oct-Dec;23(4):232-234

Authors: Tijani KH, Ojewola RW, Orakwe DE, Oliyide AE

Abstract
A horseshoe kidney (HSK) is the most common congenital renal fusion anomaly. HSKs are more likely than normal kidneys to have associated problems of stones, ureteropelvic junction obstruction, stasis and infection. However, they do not have an increased incidence of renal cell carcinoma when compared to normal kidneys. Due to its rarity, accurate diagnosis may be difficult. Of similar significance is the fact that problems may arise during surgery on these kidneys due to altered anatomy and aberrant blood supply. We report a case of HSK with a renal tumour in a 69-year-old woman and highlight our challenges in the management of the case. To the best of our knowledge, this is the first reported case of a tumour in an HSK in West Africa.

PMID: 28000646 [PubMed - indexed for MEDLINE]

Targeting MEK in a translational model of histiocytic sarcoma.

Mol Cancer Ther. 2018 Aug 22;:

Authors: Takada M, Hix JML, Corner S, Schall PZ, Kiupel M, Yuzbasiyan-Gurkan V

Abstract
Histiocytic sarcoma in humans is an aggressive orphan disease with a poor prognosis as treatment options are limited. Dogs are the only species that spontaneously develops histiocytic sarcoma with an appreciable frequency, and may have value as a translational model system. In the current study, high throughput drug screening utilizing histiocytic sarcoma cells isolated from canine neoplasms identified these cells as particularly sensitive to a MEK inhibitor, trametinib. One of the canine cell lines carries a mutation in PTPN11 (E76K), and another one in KRAS (Q61H), which are associated with the activation of oncogenic MAPK signaling. Both mutations were previously reported in human histiocytic sarcoma. Trametinib inhibited sensitive cell lines by promoting cell apoptosis, indicated by a significant increase in caspase 3/7. Furthermore, in vitro findings were successfully re-capitulated in an intrasplenic orthotopic xenograft mouse model which represents a disseminated aggressive form of histiocytic sarcoma. Mice with histiocytic sarcoma xenograft neoplasms that were treated with trametinib had significantly longer survival times. Target engagement was validated as activity of ERK, downstream of MEK, was significantly downregulated in neoplasms of treated mice. Additionally, trametinib was found in plasma and neoplastic tissues within projected therapeutic levels. These findings demonstrate that in dogs, histiocytic sarcoma may be associated with a dysfunctional MAPK pathway, at least in some cases, and may be effectively targeted through MEK inhibition. Clinical trials to test safety and efficacy of trametinib in dogs with histiocytic sarcoma are warranted, and may provide valuable translational information to similar diseases in humans.

PMID: 30135215 [PubMed - as supplied by publisher]

USE OF ELECTRONIC HEALTH RECORDS TO CHARACTERIZE A RARE DISEASE IN THE U.S.: TREATMENT, COMORBIDITIES, AND FOLLOW-UP TRENDS AMONG PATIENTS WITH A CONFIRMED DIAGNOSIS OF ACROMEGALY.

Endocr Pract. 2018 Jun;24(6):517-526

Authors: Silverstein JM, Roe ED, Munir KM, Fox JL, Emir B, Kouznetsova M, Lamerato LE, King D

Abstract
OBJECTIVE: Understanding of acromegaly disease management is hampered in the U.S. by the lack of a national registry. We describe medical management in a population with confirmed acromegaly.
METHODS: Inpatient and outpatient electronic health records (EHRs) were used to create a database of de-identified patients assigned the Acromegaly and Gigantism International Classification of Diseases, 9th revision (ICD-9) code and/or an appropriate pituitary procedure code at 1 of 4 regional hospital systems over a 6- to 11-year period. Information regarding demographics, medical history, labs, procedures, and medications was collected and supplemented with a chart review to validate the diagnosis of acromegaly.
RESULTS: Of 367 patients with validated acromegaly, available records showed that during the years studied, pituitary surgery was performed on 31%, 4% received radiosurgery, and 22% were prescribed a drug indicated for acromegaly. Insulin-like growth factor-1 (IGF-1) levels were measured in 62% of patients, 83% of whom had at least 1 normal value. Coded comorbidities reflect those reported previously in patients with acromegaly, with the exception of esophageal reflux in 20% of patient records. Fewer data regarding acromegaly-specific medications and testing were available for patients aged 65 and older.
CONCLUSION: AcroMEDIC is a U.S. multisite retrospective study of acromegaly that captured medical management in the majority of patients included in the cohort. Chart review highlighted the importance of verification of coded diagnoses. Most of the acromegaly-related comorbidities identified here are known to increase with age and obesity. Patients ≥65 appeared to have less active management/monitoring of their disease. Medical attention should be directed to this population to address evolving needs over time.
ABBREVIATIONS: AcroMEDIC = Acromegaly Multisite Electronic Data Innovative Consortium; BMI = body mass index; CCI = Charlson Comorbidity Index; EHR = electronic health record; GH = growth hormone; GHRA = growth hormone receptor antagonist; ICD-9 = International Classification of Diseases, 9th revision; IGF-1 = insulin-like growth factor-1; SSA = somatostatin analogue.

PMID: 29624099 [PubMed - indexed for MEDLINE]

Bilateral testicular torsion in a 36-week neonate.

BMJ Case Rep. 2018 Feb 07;2018:

Authors: Clarke MJH, Crocker S, Bartle DG, Apsey J

Abstract
A male neonate born after uncomplicated vaginal delivery at 36 weeks' gestation was noted to have large and firm testicles bilaterally on routine examination. A testicular ultrasound scan was subsequently organised that showed detailed appearances consistent with bilateral testicular torsion. This was thought to have taken place antenatally and as such was unfortunately not suitable for intervention. The patient was therefore managed conservatively with the testicles left to involute naturally. He was started on testosterone replacement therapy after follow-up when gonadotrophin levels were found to be raised and testosterone low (suggesting absent testicular function) and will be closely followed up regarding his future development which is normal to this point.

PMID: 29437711 [PubMed - indexed for MEDLINE]

14 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 2018/08/23

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.

[Significance of whole exome sequencing in the diagnostics of rare neurological diseases - own experiences through a case presenting with ataxia].

Orv Hetil. 2018 Jul;159(28):1163-1169

Authors: Balicza P, Grosz Z, Bencsik R, Illés A, Gál A, Gézsi A, Molnár MJ

Abstract
Next generation sequencing (NGS) technologies reshape the diagnostics of rare neurological diseases. In the background of certain neurological symptoms, such as ataxia, many acquired and genetic causes may be present. Variations in a given gene can present with variable phenotypes, too. Because of this phenomenon, the conventional one gene sequencing approach often fails to identify the genetic background of a disease. Next generation sequencing panels allow to sequence 50-100 genes simultaneously, and if the disease stratification is not possible based on the clinical symptoms, whole exome sequencing can help in the diagnostic of genetic disorders with atypical presentation. This case study is about the exome sequencing of a patient with cerebellar ataxia. Genetic investigations identified rare variants in the SPG11 gene in association with the clinical phenotype, which gene was originally described in the background of hereditary spastic paraparesis. Our article highlights that in certain cases the variability of the leading presenting symptom makes it hard to select the correct gene panel. In our case the variants in the gene, formerly associated to hereditary spastic paraparesis, resulted in cerebellar ataxia initially, so even an ataxia NGS gene panel would not detect those. Orv Hetil. 2018; 159(28): 1163-1169.

PMID: 29983107 [PubMed - indexed for MEDLINE]

Telephone health services in the field of rare diseases: a qualitative interview study examining the needs of patients, relatives, and health care professionals in Germany.

BMC Health Serv Res. 2018 02 09;18(1):99

Authors: Babac A, Frank M, Pauer F, Litzkendorf S, Rosenfeldt D, Lührs V, Biehl L, Hartz T, Storf H, Schauer F, Wagner TOF, Graf von der Schulenburg JM

Abstract
BACKGROUND: Rare diseases are, by definition, very serious and chronic diseases with a high negative impact on quality of life. Approximately 350 million people worldwide live with rare diseases. The resulting high disease burden triggers health information search, but helpful, high-quality, and up-to-date information is often hard to find. Therefore, the improvement of health information provision has been integrated in many national plans for rare diseases, discussing the telephone as one access option. In this context, this study examines the need for a telephone service offering information for people affected by rare diseases, their relatives, and physicians.
METHODS: In total, 107 individuals participated in a qualitative interview study conducted in Germany. Sixty-eight individuals suffering from a rare disease or related to somebody with rare diseases and 39 health care professionals took part. Individual interviews were conducted using a standardized semi-structured questionnaire. Interviews were analysed using the qualitative content analysis, triangulating patients, relatives, and health care professionals. The fulfilment of qualitative data processing standards has been controlled for.
RESULTS: Out of 68 patients and relatives and 39 physicians, 52 and 18, respectively, advocated for the establishment of a rare diseases telephone service. Interviewees expected a helpline to include expert staffing, personal contact, good availability, low technical barriers, medical and psychosocial topics of counselling, guidance in reducing information chaos, and referrals. Health care professionals highlighted the importance of medical topics of counselling-in particular, differential diagnostics-and referrals.
CONCLUSIONS: Therefore, the need for a national rare diseases helpline was confirmed in this study. Due to limited financial resources, existing offers should be adapted in a stepwise procedure in accordance with the identified attributes.

PMID: 29426339 [PubMed - indexed for MEDLINE]

Schnitzler syndrome co-occurring with idiopathic multicentric Castleman disease that responds to anti-IL-1 therapy: A case report and clue to pathophysiology.

Curr Res Transl Med. 2018 Aug 11;:

Authors: Soudet S, Fajgenbaum D, Delattre C, Forestier A, Hachulla E, Hatron PY, Launay D, Terriou L

Abstract
Patients with HHV-8-negative/idiopathic multicentric Castleman disease (iMCD) experience systemic inflammatory symptoms and polyclonal lymphoproliferation due to an unknown etiology. Schnitzler's syndrome (SS) is characterized by recurrent urticarial rash, monoclonal IgM gammopathy, and other clinical signs of inflammation. To our knowledge, we report the first case of iMCD associated with SS and the fourth case of anakinra inducing a complete response for an iMCD patient. A forty-four year old woman with a history of a recurrent urticarial rash, presented to our hospital complaining of 6 months of night sweats, fever, chronic urticaria, iliac bone pain, and generalized lymphadenopathy. An IgM Kappa monoclonal component was measured at 7.8g/L. A lymph node biopsy revealed histopathological features consistent with the plasma cell variant of iMCD. She was diagnosed with SS and iMCD. Anti-IL-1 treatment with anakinra (100mg/day) was introduced. Within 48h, we observed improvement in the fever and the urticarial rash. By one month, we considered the patient in complete remission. Two years later, the remission is persistent while the patient is still under therapy. Though this is only the fourth reported case of anakinra in iMCD, this is yet another case demonstrating the effectiveness of anti-IL-1 blockade in SS. We hypothesize that uncontrolled cytokine production is responsible for both the SS and the iMCD. The etiologies of SS and iMCD are unknown, and future research is necessary.

PMID: 30108026 [PubMed - as supplied by publisher]

Anesthesia in a child with suspected peroxisomal disorder.

Anaesthesist. 2017 Dec;66(12):944-947

Authors: Englbrecht JS, Maas M

Abstract
We present the case of an 8‑year-old female child with suspected peroxisomal disorder requiring general anesthesia for adenotomy, paracentesis and brainstem-evoked response audiometry. Peroxisomes are small intracellular organelles that catalyse key metabolic reactions. Peroxisomal disorders are a heterogeneous group of rare genetic diseases. Anesthesia can be challenging as adrenal insufficiency, mental retardation, muscle weakness, risk of pulmonary aspiration, airway complications, seizure disorders and altered pharmacokinetics and pharmacodynamics can occur in these patients but guidelines for anesthesia do not exist due to the heterogeneity and rarity of these diseases and case reports are rare. Anesthesia was induced by sevoflurane via a face mask, followed by remifentanil and rocuronium for oral intubation after intravenous access was obtained. Anesthesia was maintained with sevoflurane and remifentanil. Dexamethasone was given for prophylaxis of postoperative nausea and vomiting as well as perioperative adrenal crises. Piritramide was given for postoperative analgesia. With this approach anesthesia was uneventful. The trachea was extubated with the patient awake and she was taken to the recovery room in a stable condition. The classification and breadth of clinical manifestations of peroxisomal disorders is complex and briefly summarized. Anesthesiologists should consider characteristics of their particular patient's form of peroxisomal disorder, as this may greatly influence procedural planning.

PMID: 29119207 [PubMed - indexed for MEDLINE]

Low-grade myofibroblastic sarcoma of the thoracic spine: report of an extreme rare case.

Br J Neurosurg. 2017 Dec;31(6):731-733

Authors: Hadjigeorgiou GF, Samaras V, Varsos V

Abstract
Primary low-grade myofibroblastic sarcoma of the bone seems to be extraordinary rare. A search of the literature revealed only 11 prior cases. The most common location is distal femur, followed by the iliac wing. In the present study, we report an unusual case of a low-grade myofibroblastic sarcoma located in the thoracic spine of a 55-year-old male and we discuss its radiological, light microscopical and immunohistochemical features.

PMID: 27535494 [PubMed - indexed for MEDLINE]

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 2018/08/14

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.

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 2018/08/14

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.

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 2018/08/11

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 2018/08/11

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.

Morvan's syndrome-is a pathogen behind the curtain?

Neurol Sci. 2018 Aug 09;:

Authors: Singh R, Das P, Kaur U, Misra A, Choudhury A, Manna S, Gaude R, Gautam D, Gambhir IS, Chakrabarti SS

Abstract
Morvan's syndrome is a rare syndrome of likely autoimmune etiology characterized by peripheral nerve hyperexcitability, dysautonomia, insomnia, and fluctuating delirium with prominent hallucinations. Since its first mention in 1890, less than 100 cases have been described in literature. The largest existing review includes details of 29 cases. This case series describes 4 cases (M = 4) of Morvan's syndrome which presented between May and November 2017 to a single tertiary care referral teaching hospital in north India. All the four patients manifested behavioral abnormalities, sleep disturbances, hallucinations, autonomic dysfunction, and clinical signs of peripheral nerve hyperexcitability, mostly as myokymia. Two of the patients had Anti-CASPR2 (contactin-associated protein 2) antibodies. Three of them had electromyography features of peripheral nerve hyperexcitability and only one had elevated cerebrospinal fluid protein level. We hypothesize that Morvan's syndrome and other less characterized autoimmune encephalitis/peripheral nervous system syndromes may have infectious triggers. A possible viral trigger may result in generation of autoantibodies which result in the typical manifestations. We base these hypotheses on the finding of four cases of an orphan disease within a short period of time in a limited geographical distribution.

PMID: 30090985 [PubMed - as supplied by publisher]