Infantile-onset Pompe disease (IOPD) or acid maltase deficiency is a rare metabolic disorder. It is caused by a deficiency in functioning of the enzyme acid alpha-glucosidase and leads to the accumulation of glycogen in the liver, heart, muscle, and other tissues. Myozyme is an effective drug, but it imposes a heavy financial burden on societies and healthcare systems. Therefore, this study was conducted to analyze the cost-effectiveness of Myozyme compared to conventional therapy for the treatment of IOPD. PubMed, Scopus, Web of Science, and Cochrane library databases were searched on December 2018 to identify the effectiveness of Myozyme versus conventional therapy. Then, a cost-effectiveness and a cost utility study were conducted in patients suffering from IOPD. In this cost effectiveness and cost utility analysis, Markov and decision tree models were used for modeling. Model parameters were obtained from international data, and the perspective of the payer was considered. Every cycle was one year; the model was run for 22 cycles. TreeAge pro 2011 was used for analysis. Finally, one-way and probabilistic sensitivity analyses were performed. Two papers were included and 39 patients were evaluated as the treatment group in both studies. Results revealed the effectiveness of Myozyme. Results also revealed a wide range of adverse reactions. Enzyme replacement therapy (ERT) resulted in 4.21038 quality-adjusted life years (QALY) per $381,852. The incremental cost per QALY was $96,809 and the incremental cost per life years gained (LYG) was 74,429 over a 22-year time horizon. Sensitivity analysis indicated the robustness of the results. Myozyme is effective for IOPD and could increase the life expectancy of patients significantly. However, since the calculated incremental cost per QALY was 17 times higher than the GDP per capita of Iran, Myozyme is not cost effective in Iran.

Acute intermittent porphyria (AIP) is a rare inherited metabolic disease associated with heme metabolism. Primary Sjogren's syndrome (PSS) is a common autoimmune disease. The combined presence of AIP and PSS complicates treatment. A rare case of concomitant AIP and PSS is reported in this paper. A 30-year-old woman with AIP had recurrent acute abdominal pain, nausea and vomiting, constipation, persistent chest, back, and waist pain, red urine, positivity for porphobilinogen (PBG) in urine and a pathogenic mutation of the HMBS gene. Two and a half years after she was diagnosed with AIP, she was diagnosed with PSS based on dryness of the eyes and mouth, the elevation of immunoglobulins (IgG and IgA) and positive results on an anti-SS-A antibody test, an anti-SS-B antibody test, Schirmer's test and a labial gland biopsy. A mutation in the HMBS gene was detected in the patient and her cousin, but the patient had more severe AIP and more severe symptoms (such as epilepsy and a limp), which may be related to the co-morbidity of PSS. According to her PSS activity score, the patient had an ESSDAI score of 9 and required systemic treatment. However, potential medications were limited by AIP, so mycophenolate mofetil was eventually added to delay the progression of the primary disease.

A very rare case of acute intermittent porphyria (AIP) co-existing Turner syndrome (TS) is reported for the first time. A 32-year-old woman was diagnosed with AIP due to recurrent acute abdominal pain, red urine and pathogenic mutation of Hydroxymethyl synthetase (HMBS) gene. At the same time, TS was confirmed by Karyotype analysis results of 46,X,i(X)(q10), which accompanied by primary amenorrhea, elevated serum concentrations of follicle-stimulating hormone (FSH). Since the first attack of AIP, the patient has been increasingly depressed, and Psychiatry identified major depression. Duloxetine was chosen after careful deliberation, and the patient's mood stabilized. AIP had not recurred after half a year. Since sex hormones are the exacerbating factor of acute attack of AIP, sex hormone replacement therapy for TS was not administered. In conclusion, the conditions of AIP co-existing TS are complicate, and the treatment still needs to be improved by multiple disciplines in the follow-up.

Klinefelter syndrome (KS) variants often share common features with classical syndrome but some of these variants present with a distinct phenotype. The incidence of sex chromosome tetrasomy and pentasomy are very less and generally diagnosed after prepubertal age. The early diagnosis of complex and unclassified syndromes and it's correlation with genotype is necessary for personalized treatment as well as genetic counselling of the affected families. We describe clinical presentation, and genetic diagnosis of two cases of variant KS. Our first case, a 4 year old male child presented with generalized tonic-clonic seizures (GTCSs), delayed milestones and dysmorphic features while case 2, a-21 years old male who had history of seizures and delayed puberty came to our lab for genetic diagnosis. The chromosomal analysis of case 1 and 2 showed 49,XXXXY and 48,XXYY karyotype respectively. The karyotype results were confirmed with fluorescence in situ hybridization (FISH) and array-CGH analysis. The FISH results were found to be consistent with karyotype but the array-CGH results showed the extra gain of region Yp11.2 in case 1 while the extra gain of region Xp22.33 in case 2. The cases were confirmed as variant KS on the basis of additional sex chromosomes and clinical presentation of deteriorated brain development. The present study suggests that the high doses of sex chromosome linked genes including pseudoautosomal region (PAR) caused the abnormal brain development. The combination of molecular techniques should be utilized for the diagnosis of such complex cases to understand the genotype-phenotype correlation and appropriate genetic counseling.

Alzheimer's disease (AD) is the most common cause of dementia with around 50 million people suffering from this disease worldwide. Mutations in the ATP-binding cassette sub-family A member 7 (ABCA7) have been reported to cause susceptibility to AD 9 (OMIM #608907). In this study, we report a novel variant in ABCA7 in a Saudi patient with susceptibility to AD 9 and a strong family history of neurodegenerative disorders, which may be explained by the same variant. We studied a single 57-year-old female patient with typical symptoms of AD supported by MRI findings from a Saudi family with a positive history of a similar disease in multiple individuals. The case study was conducted in King Abdulaziz Medical City in Jeddah, Saudi Arabia. Whole-exome sequencing identified the novel heterozygous variant c.3706C>T p.(Avg 1236Cys) in the ABCA7 gene, which leads to an amino acid exchange. Furthermore, bioinformatics in silico programs predict a pathogenic effect for this variant. To the best of our knowledge, the variant has not been described in the literature so far as evidenced by a thorough literature review using multiple databases such as Ovid, Medline, EMBASE, ProQuest, Science Direct, Google Scholar, and PubMed. In this article, we reported a middle-aged Saudi woman with a novel variant in ABCA7 who had clinical features of both AD and Parkinson's disease. Given the reported function of this gene, it is most likely that it is etiological and pathological because of the presenting complex neurological disease due to decreased clearance of β-amyloid and α-Synuclein. We illustrate the importance of this interesting gene that could be implicated in several neurodegenerative disorders.

The suprarenal retroperitoneum and adrenal gland is a rare site of origin for benign schwannomas which frequently present as larger and more aggressive lesions than schwannomas identified elsewhere. These tumors are often surgically excised. We present a case of an 81-year-old asymptomatic man presenting with an incidental 10 cm left suprarenal retroperitoneal mass identified on CT. The mass was indiscernible from the adrenal gland, demonstrating heterogeneous enhancement with a centrally cystic/necrotic core, and punctate calcifications. Subsequent core needle biopsy demonstrated a benign adrenal schwannoma. The lesion has been managed conservatively with imaging follow up and without complication. DISCUSSION: Our review of the literature identifies 121 reported in vivo benign adrenal and suprarenal schwannomas published to date with imaging features available for 90 cases (74%). All cases were encapsulated with the average size measuring over 6.5 cm. Fifteen percent (13/84) of reported lesions measured over 10 cm at presentation. Punctate calcification was present in 50% (26/52) of reporting cases. Nearly 50% (40/86) of cases demonstrate cystic/necrotic appearances on imaging. Despite aggressive appearances, our case demonstrates that biopsy and surveillance may represent a reasonable alternative to surgery in suboptimal surgical candidates.

Primary central nervous system lymphoma (PCNSL) is a rare malignant tumor of the central nervous system. It is associated with poor prognosis. Early diagnosis and subsequent planning of adequate treatment strategy are relevant to improve survival and reduce neurological deficit. Specifically, there are no reports of successful endoscopic biopsy for PCNSL of the corpus callosum in the splenium with bilateral visuomotor ataxia. An 74-year-old woman presented to our hospital with anorexia, depression and ataxia beginning six months earlier. Head computed tomography and magnetic resonance imaging showed malignant tumor suspected in the corpus callosum. Endoscopic biopsy was performed via the low parieatal approach, suspecting GBM or PCNSL. She had no new postoperative neurological deficits and was pathologically diagnosed with diffuse large B-cell lymphoma (DLBCL). She is currently undergoing radiation chemotherapy with a modified Rankin Scale score of 2. Regarding preoperative symptoms, ataxia was considered to be bilateral visuomotor ataxia caused by damage to the corpus callosum in the splenium, and anorexia and depression were considered symptoms of the surrounding limbic system. Delay in the diagnosis of PCNSL can lead to a poor prognosis. Visuomotor ataxia should also consider the potential for the corpus callosum in the splenium lesion, including PCNSL, and appropriate imaging and pathological diagnosis with endoscopic biopsy can contribute to a good clinical outcome.

Symptomatic hypocalcemia is frequently encountered in the Emergency Department, necessitating admission. It has a variety of underlying etiologies, with hypoparathyroidism and vitamin D deficiency being the most common. However, rarer etiologies such as pseudohypoparathyroidism, as was present in the current case, should not be overlooked. Reported here is a case of a young female patient presenting with generalized tonic clonic seizures. Electrocardiography revealed a prolonged QT interval which pointed towards a metabolic cause, and this was confirmed by laboratory results which indicated a low calcium level. A parathyroid pathology was obvious as the phosphate level was elevated. Pseudohypoparathyroidism, rather than hypoparathyroidism, was identified since the parathyroid hormone level was elevated. Other relevant differential diagnoses were excluded. The patient was treated with intravenous calcium initially and given regular oral calcium, calcitriol, and sevelamer.

A 26-year-old Chinese man was admitted to this clinic due to decreased vision in his right eye for 4 days and painful protrusion in his left eye for 20 days. He had no perception of light in his left eye and perception of hand motion (HM) in his right eye. Examinations revealed that the left eye's lens and iris had protruded, and corneoscleral perforation. The right eye had an anterior chamber reaction and severe exudative retinal detachment that were confirmed by fluorescein angiography. Systemic examinations failed to identify a cause. The presumptive diagnosis was sympathetic ophthalmia of the right eye. Therefore, systemic steroid treatment was administered and enucleation of the left eye was performed. Although steroid treatment had been initiated, exudative detachment did not vary markedly. A pathological examination of the left eye revealed ocular tuberculosis, and anti-tuberculosis treatment resulted in a gradual reduction in subretinal fluid as well as improved vision.

Angiolipomas are slow-growing, soft tissue tumors consisting of mature adipocytes and thin-walled blood vessels. While most angiolipomas are subcutaneous lesions in the trunk and upper extremities, intraosseous angiolipomas are rare at cranial site. We present the case of a 61-year-old female with an enlarging lesion in the left frontoparietal skull following minor head trauma. Radiography confirmed an expansile, enhancing, spiculated bony lesion in the left frontoparietal calvarium with extension outside the cortex into the soft tissues. She underwent a craniectomy for complete resection of the calvarial mass, which was histologically composed of mature adipocytes and disorganized blood vessels highlighted by an immunophenotype positive for S100 and CD34, respectively, consistent with a cranial intraosseous angiolipoma. The review of the literature that reported five cases of cranial intraosseous angiolipoma with our case representing the sixth case is discussed.

Rare diseases (RD) of genetic origin are raising public health concern contributing to a massive economic burden in India. Establishing Specialty Centers to bridge the RD community with apex centers is felt as a need in developing countries. Hence a Comprehensive Rare Disease Care (CRDC) model was set up at the department of pediatrics under Center for Human Genomics and Counseling at a medical college hospital in South India. The patients suspected to have genetic disease were evaluated as per the work flow of the designed model. The utilization statistics depict the outcome of this model. In the face of limited resources, it was possible to establish a functional RD unit with meticulous planning, supportive administration and trained interdisciplinary staff. A scalable prototype that could be replicated in other Medical colleges and Hospitals of India is described.

Testicular germ cell tumors (TGCTs) are the most frequent solid malignant tumors in men 20-40 years of age and the most frequent cause of death from solid tumors in this age group. Recent studies have underscored the fact that miRNA deregulation is a feature of carcinogenesis, including TGCT development and progression. MiRNAs are a group of small noncoding RNAs that bind to the 3′-untranslated region (UTR) of the targeted mRNAs, thus causing mRNA degradation or the inhibition of its translation, regulating gene expression in a temporal and tissue-specific manner. However, few miRNAs have been found to play key roles in TGCTs; recently, other miRNAs have been identified, representing novel potential therapeutic targets.