The Report of Three Rare Cases of the Niemann-pick Disease in Birjand, South Khorasan, Eastern Iran

How to Cite This Article: Noroozi Asl S, Vakili R, Ghaemi N, Eshraghi P. The Report of Three Rare Cases of the Niemann-pick Disease in Birjand, South Khorasan, Eastern Iran. Iran J Child Neurol. Summer 2017; 11(3):53-56. AbstractNiemann–Pick disease type C (NP-C) is a rare neurovisceral and irreversible disease leading to premature death and disabling neurological signs. This autosomal recessive disease with incidence rate of 1:120000 is caused by mutations in either the NPC1 or the NPC2 gene, which leads to accumulation of cholesterol in body tissues especially brain and progressive neurological symptoms. NP-C is characterized by nonspecific visceral, neurological and psychiatric manifestations in infants. The neurological involvement is typically proceeded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno-or hepatosplenomegaly in infancy or childhood).Early detection of NPC is important so that therapy with miglustat can delay onset of neurological symptoms and prolong survival. We describe here three infants from Birjand, South Khorasan, eastern Iran in 2016 with splenomegaly and different neurological signs that diagnosis was confirmed by genetic study. In all of them, NPC-509 was pathologically increased. They also had an unreported homozygous mutation (c. 1415T>C, p.Leu472Pro) in exon 9 of the NPC1 gene. We found unreported homozygous mutation in NPC gene.Knowing this mutation is significant to our people. Genotype-phenotype correlations for this specific mutation needs to be further studied. References1. Mengel E, Klunemann H, Lourenco C, and et al. Niemann-Pick disease type C symptomatology: an expert-based clinical description. Orphanet J Rare Dis 2013;8:166.2. Vanier MT: Niemann-Pick disease type C. Orphanet J Rare Dis 2010;5:16.3. Di Rocco M1, Dardis A, Madeo A, Barone R, Fiumara A. Early miglustat therapy in infantile Niemann-Pick disease type C. Pediatr Neurol 2012;47(1):40-3.4. Karimzadeh P, Tonekaboni SH, Ashrafi MR, et al. Effects of Miglustat on Stabilization of Neurological Disorder in Niemann–Pick Disease Type C Iranian Pediatric Case Series. J Child Neurol 2013;28(12):1599-606.5. Wijburg F, Sedel F, Pineda M et al. Development of a Suspicion Index to aid diagnosis of Niemann-Pick disease type C. Neurology 2012;78(20):1560-7.6. Wraith JE, Imrie J. New therapies in the management of Niemann-Pick type C disease: clinical utility of miglustat. Ther Clin Risk Manag 2009;5:877-87.7. Patterson M, Hendriksz Ch, Walterfang M, et al. Recommendations for the diagnosis and management of Niemann–Pick disease type C: An update. Mol Genet Metab 2012;106(3):330-44.8. Margaret M, Destinck DJ. Lipidosis(Lysosomal storage disease). Nelson Textbook of Pediatrics. 19th ed.Philadelphia: WB Saunders Company. 2011:488-9.9. Patterson M.C, Mengel E, Wijburg F, et al. Disease and patient characteristics in NP-C patients: findings from an international disease registry. Orphanet J Rare Dis 2013;8:12

The Effects of Enzyme Replacement Therapy in Patients with Mucopolysaccharidosis Type 1: A Case Series Study

Background: Mucopolysaccharidosis type I (MPS1) is caused by mutations in the gene which encodes the enzyme alpha-L-iduronidase. Deficiency of this enzyme causes a range of clinical symptoms in patients. The main treatment for MPS1 is hematopoietic stem cell transplantation. But its morbidity and mortality rates are significant and require matched marrow donors. Another method of treating MPS1 is enzyme replacement therapy (ERT). This study was performed to determine the effects of ERT in patients with MPS1.Methods: Seven patients with MPS1, admitted in Imam Reza Hospital of Mashhad, Iran, during 2014, were included in the study. They were treated with a single dose (0.58 mg/kg) of enzyme laronidase and followed in 0, 3, 6, 9 and 12 months. The urinary glycosaminoglycan’s (GAG), shoulder and elbow joint range of motion, volume of liver and spleen, and six-minute walking test were evaluated. Data was analyzed by SPSS software (version 16.0).Results: The mean age of the patients was 22.43±5.85 months at the baseline. During follow-up, the level of urinary GAG showed a significant reduction (p=0.004), the volumes of liver (p<0.001) and spleen (p=0.004) were significantly reduced, and the result of 6-minute walking test was significantly increased (p<0.001). The side effects included generalized skin erythema as an allergic reaction in one patient and two episodes of fever during drug administration in one patient.Conclusion: According to the results, the treatment with L-iduronidase in patients with MPS1 was effective and mostly safe

Modeling of Ti-W Solidification Microstructures Under Additive Manufacturing Conditions

Additive manufacturing (AM) processes have many benefits for the fabrication of alloy parts, including the potential for greater microstructural control and targeted properties than traditional metallurgy processes. To accelerate utilization of this process to produce such parts, an effective computational modeling approach to identify the relationships between material and process parameters, microstructure, and part properties is essential. Development of such a model requires accounting for the many factors in play during this process, including laser absorption, material addition and melting, fluid flow, various modes of heat transport, and solidification. In this paper, we start with a more modest goal, to create a multiscale model for a specific AM process, Laser Engineered Net Shaping (LENS™), which couples a continuum-level description of a simplified beam melting problem (coupling heat absorption, heat transport, and fluid flow) with a Lattice Boltzmann-cellular automata (LB-CA) microscale model of combined fluid flow, solute transport, and solidification. We apply this model to a binary Ti-5.5 wt pct W alloy and compare calculated quantities, such as dendrite arm spacing, with experimental results reported in a companion paper

A Methylmalonic Acidemia Case Presenting with Acrodermatitis Enteropathica

We encountered a patient with methylmalonic aciduria associated with skin lesions resembling acrodermatitis enteropathica. This child was being fed with a low-protein diet when the skin disorder developed. A deficiency in plasma levels isoleucine, was confirmed. Supplementation of a high-caloric, protein-rich diet led to a prompt improvement of skin lesions. We assume that in our patient the skin lesions were the result of malnutrition, rather than being primarily associated with the underlying metabolic disease. To our knowledge, few reports are so far available concerning methylmalonic aciduria complicated by skin eruptions

Hypercalciuria, a promoting factor to urinary tract infection in children

<b>Aim:</b> Urinary tract infection (UTI) is one of the most common diseases of urogenital tract in children. Detecting predisposing factors for UTI takes an important place in managing patients with UTI. Recently, a few studies emphasized on idiopathic hypercalciuria (IH) as a predisposing factor for UTI and dysfunctional voiding. Therefore, we carried out a survey to find out whether non-calculus IH is a contributing factor in children with the first attack of pyelonephritis. <b> Materials and Methods: </b> This is a case-control study carried out on 60 children aged 2-11 years admitted at St Al-Zahra hospital, Isfahan, Iran, with the first episode of upper UTI and 200 age- and gender-matched normal healthy children between September 2003 and February 2005. We used second fasting spot urine sample to measure calcium and creatinine. Two urine samples were obtained one week apart to increase the accuracy of measurement. All samples were collected after at least 6 weeks of completing the treatment course of pyelonephritis. Ultrasound examination and VCUG were performed in all patients before entering the survey as case group to rule out obstruction and VUR. <b> Results: </b> Mean age of case and control group were 4.86 &#177; 3.08 years and 4.22 &#177; 2.9 years, respectively. The mean calcium to creatinine ratio (Ca/Cr) in case and control group were 0.308 &#177; 0.21 and 0.208 &#177; 0.12 mg/mg, respectively, <i>P</i> &lt; 0.001. The difference between the mean values of these two groups was significant only in age group &#8804;6 years, <i>P</i> &lt; 0.0001 and odds ratio was 2.1 (95&#x0025; CI 1.03-7.8). After determining the mean values of urine Ca/Cr ration according to both age groups and gender, it was cleared that only significant difference was related to male &#60; 6 years. <b>Conclusion: </b> The likelihood of hypercalciuria should be assessed especially in male children with UTI and without any urinary tract obstruction

Association of Pediatric Stress Hyperglycemia with Insulin Metabolism Disorders

Introduction: Transient hyperglycemia is a condition that happens during acute physiologic stress in children.  The aim of this study is to determine if there is any relation between stress hyperglycemia and diabetes mellitus and metabolic syndrome in pediatric patients.   Materials and Methods:  The study was performed on children hospitalized in Amirkola pediatric hospital, North of Iran, between February 2011 to January 2013. Children with a history of stress hyperglycemia were studied for the presence of metabolic syndrome or Anti GAD65 Autoantibodies. A total of 50 patients were studied.   Results: None of our patients had developed type 1 diabetes. OGTT was normal in all patients. Metabolic syndrome was present in 2 cases (4%). The prevalence of insulin resistance was 16%. The most common metabolic abnormality noted was hypertriglyciredemia and one patient was positive for GAD 65 autoantibody.  Conclusion: According to our data children with stress hyperglycemia do not appear to be at increased risk of developing type 1 diabetes but insulin resistance is relatively common in these patients

Type 1 Tyrosinemia with Hypophosphatemic Rickets; a Case Report

Background: Tyrosinemia type 1 is an autosomal recessive metabolic disorder, which typically affects liver and kidneys. It is caused by a defect in fumarylacetoacetate hydrolase or fumarylacetoacetase (FAH) enzyme, the final enzyme in the tyrosine degradation pathway. The disease typically manifests as early onset type in early infancy with acute hepatic crisis with hepatomegaly and bleeding tendency. In 1992, a new drug orfadin (NTBC, Nitisinone) which is a potent inhibitor of 4 hydroxy phenyl pyrovate dioxygenase has revolutionized the treatment of tyrosinemia type 1 and is now the mainstry of therapy. Case presentation: Our case was a girl in midchidhood period with profound rickets and slowly progressing liver disease who presented with difficulty walking and weakness of muscles. She had an elevated serum tyrosine and urinary succinylacetone, which confirmed the diagnosis of tyrosinemia type 1 and after treatment with NTBC significant remission, was achieved

Mothers’ lived experience of caring for children with inborn errors of amino acid metabolism

Abstract Background Inborn errors of amino acid metabolism are chronic conditions that have many sequels. Mothers of these children are facing different challenges which are underdetermined. This study was done to explore lived experience of mothers caring for these children. Methods This is an interpretive phenomenology with van Manen’s approach which has 6 steps. Data were gathered by convenience and purposeful sampling. Nine mothers with different experiences were interviewed and the interviews were audiotaped. Results Six final themes were revealed from the exploring mothers’ experiences including the future tied to the past, psychosis in the shadow of a lost ideal child, rebellion and blaming, the ways of escaping difficulties, self-forgetting in the shadow of full-time care, passing difficulties in the duality of hope-hopelessness, caring in a continuum of isolation-socialization. Conclusion Mothers have multiple challenges in taking care of their children, especially psychologically and financially. So, nurses must plan programs for helping mothers of children with inborn errors of amino acid metabolism to reduce the effects of disease on mothers and consequently the children and the whole family

Identification of mutations in Iranian patients’ DAX-1 gene with X-linked adrenal hypoplasia congenital

Objective(s): X-linked adrenal hypoplasia congenital (X-linked AHC) is a rare disorder, characterized by infantile-onset acute primary adrenal insufficiency and hypogonadotropic hypogonadism (HH) at an average age of three weeks and onset in roughly 40% is in childhood. Its cause is an inactivating mutation in the (nuclear receptor subfamily 0, group B, member 1) NR0B1 gene, DSS (dosage sensitive sex)-AHC vital region on the X-gene 1. Subjects and methods: In the present study, the (dosage-sensitive, sex reversal, adrenal hypoplasia congenital, important region on the X-chromosome, gene 1) DAX-1 gene from four Iranian patients with X-linked AHC was analyzed by means of polymerase chain reaction (PCR) and direct sequencing. Results: We identified a polymorphism (Rs6150) which encodes a cysteine (Cys) at position 38, a de novo deletion, c.849-928del79 bp, c.849-856ins, (TGCTGCA) mutation and a missense mutation, Leu262Gln, which encodes a leucine (Leu) for glutamine (Gln) at position 262. Conclusion: Both mentioned mutations are located at crucial and functional region DAX1 protein. They are detected in the C-terminal region of DAX1 protein which is involved by the conserved amino acid chain as well as transcriptional silencing domain. By considering other investigation, mutations in this region probably lead to produce a misfolded protein. Consequently, the misfolded protein would not work influentially in order to inhibit some gene expression. As a result, our findings will expand the variety of DAX1 mutations. On the other hand, it is revealed that these mutations play a key role in the pathogenesis of AHC, thus, recognizing these new mutations will facilitate the patients prognosis producer as well as raising the clinical knowledge about this rare disease