Gorham-Stout disease causes gradual bone loss (osteolysis) due to an abnormal overgrowth of lymphatic vessels. This rare disease is usually seen in younger people. The etiopathology of Gorham-Stout disease remains unclear. The disease is pathologically characterized by the proliferation of the vascular or lymphatic vessels and, finally, bone matrix destruction. These pathological changes lead to the presence of massive osteolysis on plain radiographs. Thus, plain radiograph findings may lead physicians to consider tumoral conditions, especially metastasis. There are several other conditions on the differential diagnosis list of massive osteolysis, such as metabolic, infectious, malignant, and immunological conditions. The treatment of the disease is symptom-based, but there is no consensus. Pharmacological methods should be considered first-line treatment. In this report, a case of Gorham-Stout disease, which is treated by pharmacological methods is presented. During the one and half year follow-up, the local control of the disease is achieved without any surgical intervention. Read the full article here.
Glucagon cell hyperplasia and neoplasia (GCHN) is the name of an endocrine receptor disease, whose morphology was first described in 2006. Three years later this rare disease was found to be to be caused by an inactivating mutation of the glucagon receptor (GCGR) gene. Functionally, the genetic defect mainly affects glucagon signaling in the liver with changes in the metabolism of glycogen, fatty acids and amino acids. Recent results of several studies in GCGR knockout mice suggested that elevated serum amino acid levels probably stimulate glucagon cell hyperplasia with subsequent transformation into glucagon cell neoplasia. This process leads over time to numerous small and some large pancreatic neuroendocrine tumors which are potentially malignant. Despite high glucagon serum levels, the patients develop no glucagonoma syndrome. In 2015 GCHN was identified as an autosomal recessive hereditary disorder. Read the full article here.
Benign recurrent aseptic meningitis is a rare condition characterized by recurring, self-limited episodes of aseptic meningitis. Meningeal irritation typically occurs first, accompanied by fever and mononuclear cell pleocytosis. The diagnosis is only made after other known causes of lymphocytic meningitis have been excluded. Resolution typically occurs within two to seven days without residual neurological deficit. Aseptic meningitis is most frequently caused by viruses; Mollaret’s meningitis has been linked to the herpes simplex virus 2 (HSV 2). It is unclear if prophylactic medication is indicated for these patients. In this report a patient who was experiencing her seventh episode of aseptic meningitis is described. Read the full article here.
Spinal muscular atrophy (SMA) could be classified as 5q and non-5q, based on the chromosomal location of causative genes. A rare form of non-5q SMA is an autosomal-recessive condition called spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME), phenotypically characterized by myoclonic and generalized seizures with progressive neurological deterioration. SMA-PME is a clinically heterogeneous disorder that arises from biallelic pathogenic variants in ASAH1 gene.
In this report following clinical and primary laboratory assessments, whole-exome sequencing is performed to detect the disease-causing variants in three cases of SMA-PME from different families.
Exome sequencing reveals two different homozygous missense mutations (c.109 C > A [p.Pro37Thr] or c.125 C > T [p.Thr42Met]) in exon 2 of the ASAH1 gene in the affected members of the families.
This study describes two different ASAH1 mutations and the clinical picture of 3 SMA-PME patients. In addition, previously reported mutations have been reviewed. This study could help to fortify the database of this rare disease with more clinical and genomic data. Read the full article here.
Rasmussen encephalitis (RE) is a rare progressive presumed autoimmune disorder characterized by pharmacoresistant epilepsy and progressive motor and cognitive deterioration. Despite immunomodulation, more than half of the patients with RE ultimately require functional hemispherotomy. In this study, the potential beneficial effects of early initiation of immunomodulation in slowing disease progression and preventing the need for surgical interventions is evaluated.
A retrospective chart review over a 10-year period is conducted at the American University of Beirut Medical Center to identify patients with RE. Five patients with only monthly to weekly seizures at the time of IVIG initiation have favorable outcomes without resorting to surgery, along with a relative preservation of the gray matter volumes in the affected cerebral hemispheres. Motor strength is preserved in those patients, and three are seizure free at their last follow-up visit.
The data in this report suggest that the early initiation of IVIG as soon as a diagnosis of RE is suspected, and particularly before the appearance of motor deficits and intractable seizures, can maximize the beneficial effects of immunomodulation in terms of controlling seizures and reducing the rate of cerebral atrophy. Read the full article here.
Diamond-Blackfan anemia (DBA) is a rare bone marrow failure syndrome, usually caused by loss-of function variants in genes encoding ribosomal proteins. The hallmarks of DBA are anemia, congenital anomalies and cancer predisposition. Although DBA usually presents in childhood, the prevalence in later life is increasing due to an expanding repertoire of implicated genes, improvements in genetic diagnosis and increasing life expectancy. To standardize and optimize care for this rare disease, in this report an updated guidance on the diagnosis and management of DBA, with a specific focus on older adolescents and adults is provided. Recommendations are based upon published literature and pooled clinical experience from three centres in the United Kingdom. Read the full article here.
Clinical trial development in rare diseases poses significant study design and methodology challenges, such as disease heterogeneity and appropriate patient selection, identification and selection of key endpoints, decisions on study duration, choice of control groups, selection of appropriate statistical analyses, and patient recruitment. Therapeutic development in organic acidemias (OAs) shares many challenges with other inborn errors of metabolism, such as incomplete understanding of natural history, heterogenous disease presentations, requirement for sensitive outcome measures and difficulties recruiting a small sample of participants. In this report strategies for the successful development of a clinical trial to evaluate treatment response in propionic and methylmalonic acidemias are reviewed. The significant challenges associated with designing a clinical trial in rare disease can sometimes be successfully met through strategic engagement with experts in the rare disease, seeking regulatory and biostatistical guidance, and early involvement of patients and families. Read the full article here.
Congenital thrombotic thrombocytopenic purpura (cTTP) is an extremely rare disease characterized by the severe deficiency of a disintegrin and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13), caused by ADAMTS13 mutations. While ADAMTS13 supplementation by fresh frozen plasma (FFP) infusion immediately corrects platelet consumption and resolves thrombotic symptoms in acute episodes, FFP treatment can lead to intolerant allergic reactions and frequent hospital visits. Up to 70% of patients depend on regular FFP infusions to normalize their platelet counts and avoid systemic symptoms, including headache, fatigue, and weakness. The remaining patients do not receive regular FFP infusions, mainly because their platelet counts are maintained within the normal range or because they are symptom-free without FFP infusions. However, the target peak and trough levels of ADAMTS13 to prevent long-term comorbidity with prophylactic FFP and the necessity of treating FFP-independent patients in terms of long-term clinical outcomes are yet to be determined. This study suggests that the current volumes of FFP infusions are insufficient to prevent frequent thrombotic events and long-term ischemic organ damage. This report focuses on the current management of cTTP and its associated issues, followed by the importance of upcoming recombinant ADAMTS13 therapy. Read the full article here.
Caroli disease is multifocal segmental dilatation of the large intrahepatic bile ducts that connect to the main duct. It is considered a rare disease with an incidence rate of 1 in 1,000,000 births. There are two types of Caroli: the first type is the simple type, Caroli disease, which includes only cystic dilatation of the intrahepatic bile ducts. The second is called Caroli syndrome, which consists of Caroli disease and congenital hepatic fibrosis and might lead to portal hypertension leading to esophageal varices and splenomegaly.
In this report a 6-year-old girl presented to the hospital with abdominal pain for the last month with abdominal enlargement is described. The patient was already diagnosed with Caroli disease and polydactyly (six fingers on each limb) when she was born. Investigations including complete blood count, blood smear, bone marrow biopsy, esophagoscopy, abdominal ultrasound, and computed tomography scan show splenomegaly associated with hypersplenism, fourth-grade non-bleeding varices, intrahepatic cystic formations in the left and right lobes, and an atrial septal defect with a left-to-right shunt. The patient is scheduled for a splenectomy after she is vaccinated with the appropriate vaccines. After follow-up for a week in the hospital, complete blood count shows an improvement.
The association of liver diseases, polydactyly, and congenital heart diseases is extremely rare and is only documented few times in the literature. Read the full article here.
Thauvin-Robinet-Faivre syndrome (TROFAS; OMIM #617107) is a rare autosomal recessive overgrowth syndrome characterized by generalized overgrowth, dysmorphic facial features, and delayed psychomotor development caused by biallelic pathogenic variants in the FGF-1 intracellular binding protein (FIBP) gene. To date, only four patients from two families have been reported. In this report, a 4-year-old male patient with generalized overgrowth and delayed developmental milestones consistent with this syndrome is presented. He has unique features that were not reported in previous patients, including drooling, recurrent pulmonary infections, chronic pulmonary disease, hyperextensible elbow joints, hypoplastic nipples, unilateral cryptorchidism, and frequent spontaneous erections. In this report a homozygous, likely pathogenic variant, c.415_ (p.Asp139AlafsTer3), which causes a frameshift in the FIBP is identified. In this article, the new observations are set out and also discuss the frequency of the characteristic findings of the syndrome in the patients so far reported. Read the full article here.