Mucopolysaccharidoses (MPS) are a group of rare lysosomal storage diseases (LSD) with multi-organic and severe symptoms. MPS occur worldwide in various forms though have relative a low incidence. The prevalent type of MPS varies among different continents, indicating that it may be associated with region and ethnic background. Undegraded glycosaminoglycans (GAGs) induced by deficiency of enzymes are the primary cause of MPS. Clinical features differ depending on the specific enzyme deficiency including coarse facial features, cognitive retardation, hepatosplenomegaly, hernias, kyphoscoliosis, corneal clouding, etc. Symptoms of different types are usually similar especially MPS I and II, but may have distinguishable features such as severe neurological problems in MPS III and hydrops fetails in MPS VII. These clinical features contribute to diagnosis, but early and precisely diagnosis in the asymptomatic stage is imperative for better outcomes. Novel approaches including urinary and blood GAG test, enzyme assay and gene test help to diagnose MPS and to determine its subtype. Hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) are conventional treatment for MPS, but are not effective at treating all MPS. Newer threatments, such as advanced ERT, gene therapy and substrate reduction therapy (SRT), improve therpeutic efficacy. In this review, we update information on the clinical manifestations, diagnosis, and treatment of the different forms of this disease in the hopes of stimulating further interest in MPS.

Peyronie's disease (PD) is a connective tissue disorder of the penis characterized by fibrosis and plaque formation within the tunica albuginea. PD is characterized by painful penile curvature that impairs sexual intercourse. Stem cell therapy is one of the recent non-invasive treatment options for patients with PD and it has promising results. Stem cells are undifferentiated cells that are capable of self-renewal and differentiation, promoting the repair of tissues via their immunomodulatory and anti-inflammatory action. Adipose-derived stem cells (ADSC) are used most widely due to their abundant tissue source and ease of isolation. Multiple studies have indicated the efficacy of stem cell therapy as a potential treatment for fibrotic diseases. Clearly, ADSCs may represent a way to treat and prevent PD in both rat and human models. Further clinical studies are needed to confirm the efficacy of stem cell therapy for PD in humans.

Wnt1 is the first member of the Wnt family that was identified. It is phylogenetically conserved and essential for oncogenesis and multiple developmental processes. This study has summarized diseases and mutations related to Wnt1. Wnt1 is involved in various cancers, genetic type XV osteogenesis imperfecta, osteoporosis, and neurological diseases. The expression of Wnt1 in normal tissues and different types of cancers and the potential survival of cancer were analyzed using experiment-based bioinformatic analysis. Systematic analysis indicated that abnormal expression of Wnt1 is significantly associated with cancers, such as kidney renal carcinoma, hepatocellular carcinoma, thyroid carcinoma, head and neck squamous cell carcinoma, and uterine corpus endometrial carcinoma. GeneMANIA and STRING predicted that 32 proteins were involved with Wnt1 in Wnt signaling pathways and sorting and secretion of Wnts. These interacting molecules significantly co-occurred according to cBioPortal analysis. Thirty-three genes with an alteration frequency of more than 50% were observed in several cancers like esophageal squamous cell carcinoma, melanoma, and non-small cell lung cancer. Functional and experiment-based bioinformatics indicated that Wnt1 may act as a target of a potential biomarker for various types of human cancers. Wnt1 and other Wnt1-related proteins and signaling pathways may be ways to treat osteoporosis.

TXNDC5 is an endoplasmic reticulum (ER)-resident chaperone that protects the endothelium from secondary effects of ER stress. Previous studies by the current authors identified TXNDC5 as a key pathological factor in promoting the inflammatory phenotype of fibroblast-like synoviocytes (FLSs) from rheumatoid arthritis (RA). However, its activity in RA FLSs under ER stress remains unclear. The current study found that TXNDC5 is responsive to ER stress in RA FLSs since its expression was induced by ER stress at both the endogenous and secretory level. A functional study indicated that silencing TXNDC5 reduced the viability of RA FLSs more markedly in the presence of ER stressors. In contrast, rhTXNDC5 attenuated a decrease in cell viability as a result of ER stress. Moreover, silencing TXNDC5 attenuated the induction of IL-6 and IL-8 from RA FLSs in response to ER stress. In addition, rhTXNDC5 induced a greater increase in VEGF production during ER stress. These findings confirm the pro-survival and pro-inflammation roles of TXNDC5 under ER stress in RA FLSs. TXNDC5 appears to act as a mediator linking ER stress and inflammation of RA.

Mutations in the GJB2 gene, which encodes the connexin26 protein and is involved in inner ear homeostasis, are the most common cause of autosomal recessive non-syndromic hearing loss (ARNSHL) in many populations. This study was aimed to determine the molecular etiology in a consanguineous Iranian family affected by profound ARNSHL. A comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in the family with 4 affected members. After extraction of genomic DNA, the entire coding region of GJB2 was directly sequenced in all family members. In silico analyses were also performed using available software tools. Sanger sequencing results showed a novel rare homozygous variant (c.109_110insG) in the GJB2 gene. This frameshift variant in exon 2 of the GJB2 gene fulfills the criteria of being categorized as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guideline. Confirmation was done with the co-segregation study and checking the frequency of the novel variant in 100 ethnically matched normal control subjects. The present study suggests that investigation of GJB2 mutations may still be useful to determine the etiology of HL in Iran.

The goal of this study was to analyze diminishment of the functional status of the skeleton, parts of organs, regions of the brain, connective tissues, and chondrocytes in patients with achondroplasia (ACH), pseudoachondroplasia (PSACH), and rickets. Three-dimensional non-linear scanning (3D-NLS) was used to analyze the functional status of patients with genetic bone disorders, including 7 patients with ACH, 3 patients with PSACH, and 3 patients with rickets. Results indicated that the percentage of patients with long bones in the decompensatory phase did not differ depending on whether they had ACH, PSACH, or rickets. Joints in the decompensatory phase did not differ in patients with ACH except for the right hip (16.67%). Various joints were in the decompensatory phase (16.7-33.3%) in patients with rickets. The thoracic vertebrae, lumbar vertebrae, and liver were in the decompensatory phase in all 3 groups of patients. Connective tissues were in the decompensatory phase in 33.33% of patients with ACH. None of the patients with PSACH had chondrocytes in the decompensatory phase but 66.67% of patients with ACH or rickets did. Regions of the brain in the decompensatory phase were most prevalent in patients with rickets or ACH but not in patients with PSACH. In conclusion, diagnosis based on 3D-NLS was able to identify the functional status of genetic bone disorders. Some areas of decompensation were common to the 3 diseases studied but other areas were specific to a given disease.

Keloid is defined as a benign dermal fibro-proliferative growth that extends outside the original wound and invades adjacent dermal tissue. Its pathogenesis is complex and much evidence suggests the influence of genetic factors, including the rs873549, rs1511412, rs940187 and rs8032158 polymorphisms associated with keloid risk in Japanese patients. The aim of our study was to investigate possible associations between rs873549, rs1511412, rs940187 and rs8032158 variants and the risk of keloid in Polish patients of European descent. The genetic polymorphisms were identified by sequencing genomic DNA extracted from peripheral blood leukocytes from 86 keloid patients and from newborn cord blood leukocytes from 100 newborns as a control group. No significant differences (p > 0.05) in the distributions of rs873549, rs1511412, rs940187 and rs8032158 alleles were found between keloid patients and newborn controls (26.7% vs. 25.5%, 9.9% vs.7.0%, 19.8% vs. 12.5%, and 41.9% vs. 33.5%, respectively). Logistic regression with adjustment for gender revealed that only the CC homozygous genotype of rs8032158 polymorphism was significantly more frequent in keloid patients as compared with controls (19.8% vs. 11.0%, respectively). Our results suggest that in contrast to Asian populations only the rs8032158 polymorphism at locus 15q21.3 is associated with the susceptibility to keloid scarring in patients of European descent.

Minor blood group incompatibility due to blood groups other than Rh(D), although an uncommon cause of neonatal hyperbilirubinemia, has the potential to cause severe hyperbilirubinemia and its sequelae in infants, if left undiagnosed and untreated. Here, we describe clinical presentation, diagnosis and treatment of three cases of minor blood group incompatibility due to anti-E and anti-c antibody. All three neonates presented with pallor, icterus and splenomegaly within the first three days of life. Investigations showed indirect hyperbilirubinemia and a positive direct coombs test. Indirect coombs test was positive in the mothers. There was no setting of ABO or Rh(D) incompatibility in any of the neonates. When tested for minor blood group incompatibility, anti E antibody was found to be responsible for hemolysis and hyperbilirubinemia in the first case, and anti c antibody was found in the second case and third case had both anti c and anti E antibodies. While hyperbilirubinemia improved with intensive phototherapy in the first two cases, the third case required a double volume exchange transfusion. On follow up, bilateral sensorineural hearing loss was seen in one of the patients. All three neonates were otherwise healthy, gaining weight and developmentally normal.

Whole Exome Sequencing (WES) has been used increasingly in genetic determination of various known and unknown genetic disorders. Various genes are involved in the development of the vascular network of retina. Assessment of a collection of these genes could be provided by WES. Here we used WES for a patient suffering vitreoretinopathy to detect the disease causing variant. Sanger sequencing has been applied for variant verification and allelic segregation. After analysis of WES data we found a new variant c.1237T>G in the FZD4 locus which causes retinopathy of prematurity and exudative vitreoretinopathy (MIM number: 133780). Sanger sequencing showed this single nucleotide variation inherited as homozygous in the patient and heterozygous in her unaffected parents. Notably, bioinformatics analysis predicted the variant as disease causing and it has not been described yet in home datasets and public SNP databases. FZD4 mutations are mostly inherited as autosomal dominant traits. Our findings showed the first autosomal recessive inheritance of the FZD4 gene related retinopathy. On the other hand, our data shed light on the significance of an Exome sequencing application as a genetic test to identify and characterize the comprehensive spectrum of genetic variation and classification for patients with retinopathies.

The recreational use of nitrous oxide (N₂O) is increasing in festivals, university parties, clubs, private residences, and parks. The abuse of N₂O has serious complications of the central and peripheral nervous system. In this article, we report a case of a 28-year-old previously healthy man who presented with a three-day history of rapidly progressive leg numbness, tingling, and weakness with gait instability and frequent falls. He had a history of marijuana use and daily inhalation of N₂O (approximately 20 whippets daily over 2-3 years). He was admitted with a presumptive diagnosis of Guillain-Barre syndrome and was started on intravenous immunoglobulin. Three days after admission, paresthesia ascended to the level of nipple line, and his weakness in the lower limb increased significantly. MRI of the cervical spine showed focal non-enhancing lesions extending from C4 to C6. Serum analysis showed low vitamin B12 level, elevated methylmalonic acid, and elevated homocysteine level. Supplemental 1000 µg/day of vitamin B12 intramuscular injections and 15 mg of folic acid tablets were given. The patient showed gradual improvement. This is a rare case of N₂O recreational abuse presenting with myeloneuropathy and mimicking Guillain-Barre syndrome. This case highlights the importance of detailed history and physical examination in patients who arrive at the hospital with clinical features of Guillain-Barre syndrome. This is especially true if there are red flags such as drug abuse or discrepancy between clinical and paraclinical (investigations) parameters. Neuroimaging of the brain and spinal cord might be necessary to score the final diagnosis in such cases.

Congenital generalized lipodystrophy (CGL) is an autosomal recessive rare disease, with a worldwide prevalence of around 1 in every 12 million people. There are several case reports of patients with CGL in Piura, a region in northern Peru; however its regional prevalence is unknown. The objective was to determine the prevalence of CGL in the region of Piura, Peru during the years 2000-2017. A descriptive, observational study was carried out. A search of clinical histories of patients with the diagnosis of CGL attended between 2000 and 2017 in the pediatric and endocrinology services of the reference hospitals of the department of Piura and in the genetic and endocrinology services of the "Instituto Nacional de Salud del Niño". A patient was considered to have CGL if they met the clinical criteria and or if they had a molecular diagnosis, in addition to patients with CGL from the department of Piura reported in previous publications. A total of 23 cases of CGL were found in Piura, the highest prevalence was in 2014 with 1.2 per 100,000 people, and by 2017 the prevalence was 0.86 per 100,000 people. In conclusion, the department of Piura has a high prevalence of CGL.

Multiple sclerosis is considered the most frequent demyelinating disorder of the Central Nervous System (CNS) among young adults, yet is very rare before 10 years old. Acute disseminated encephalomyelitis is a monophasic, polysymptomatic disorder that involves the CNS white matter with demyelinating lesions, which usually occurs after systemic viral infections. These two demyelinating diseases can present initially as an acute focal neurological syndrome and they can be difficult to distinguish. We describe a case of a nine-year-old girl that presented initially with dysphonia, gait ataxia, eyelid myokymia and brainstem disturbances. This was her second episode; the first episode was at the age of four years old. She recovered without neurological sequelae. The brain magnetic resonance imaging (MRI) demonstrated multiple demyelinating lesions in the white matter, cortical regions of the frontal lobe, periventricular distribution, internal capsule, corpus callosum and cerebellum. The purpose of the presentation of this case was to highlight the similarities between these two entities, since the clinical picture and neuroimaging are difficult to distinguish, mainly in relation to the first episode.