583V 49 16 2012EPORTSNovel Mutations causing Hyperimmunoglobulin D an - PDF document

583V 49 16, 2012EPORTSNovel Mutations causing Hyperimmunoglobulin D and Periodic FeverSyndrome R WATERHAM Hyperimmunoglobulin D and periodic fever syndrome (HIDS) is a rare, hereditaryautoinflammatory condition characterized by recurrent inflammatory episodes. We report a 584V 49 16, 2012EPORTScontrol subjects. While the alanine at position 21 is highlycause incorrect splicing. To determine their functionalactivity in patient’s fibroblasts was 8 pmol/min/mg,Due to lack of affordability and unclear efficacy,etanercept or anakinra was not administered. The childrecurrent fever, synovial or serosal inflammation, rashes,uveitis or conjunctivitis, and, in some, amyloidosis [1]. gene on chromosome 12q24 [1]. gene on chromosome 12q24 [1].different mutations in the only other report from India [3]. gene [2]. Mostgene, the most common being V337I,V337I,nucleotide changes in the alleles of the MVK gene in our gene in ourthese mutations was confirmed by the finding of a deficientMVK enzyme activity in cultured skin fibroblasts.The mechanisms by which defects in the The mechanisms by which defects in the Abnormalities noted include increased levels ofimmunoglobulins (IgD, IgA), cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-, and interferon (IFN)-],serum IL-1 receptor antagonist soluble TNF receptor, andurinary leukotriene E4 excretion [6]. The precise role ofretardation, ataxia, and epilepsy, suggesting thatmevalonic aciduria (MA, OMIM 251170) and HIDS form170) and HIDS formwith MA, patients with HIDS have residual (1-8%)enzyme activity, as is confirmed in our patient [7, 8].managed. Alt

hough HIDS is considered to be a benigncondition, treatment is difficult and largely supportive.Anti-inflammatory drugs have variable efficacy inColchicine is suggested to be effective at prolongingseverity. Similarly, beneficial effects have been ascribed totherapy with simvastatin, an inhibitor of HMG-CoAantagonist, and etanercept, the tumour necrosis factor-) inhibitor [9, 10]. More recently, demonstration ofefficacy of zaragozic acid A suggests a role for modulation suggests a role for modulationThis report highlights the need to consider familialperiodic fevers or auto-inflammatory disorders whenevaluating patients with recurrent fever, synovial orand hepatosplenomegaly. HIDS should be considered as adifferential diagnosis irrespective of family history andethnicity.1.Drenth JP, Van Der Meer JW. Hereditary periodic fever.2.Mandey SHL, Schneiders MS, Koster J, Waterham HR.3.Lawrence A, Hol F, Aggarwal A, Drenth JPH.4.Schneiders MS, Houten SM, Turkenburg M, Wanders RJ,5.Houten SM, Frenkel J, Waterham HR. Isoprenoidbiosynthesis in hereditary periodic fever syndromes and6.Drenth JPH, Goertz J, Daha MR, van der Meer JWM.7.Haas D, Hoffmann GF. Mevalonate kinase deficiencies: 585V 49 16, 2012EPORTS8.Hoffmann GF, Charpentier C, Mayatepek E, Mancini J,9.Church LD, Churchman SM, Hawkins PN, McDermott 10.Topaloðlu R, Ayaz NA, Waterham HR, Yüce A, GumrukMutation Analysis of Indian Patients with Urea Cycle DefectsUPTA *J HFrom the Genetic Unit, Department of Pediatrics, AIIMS and *Kinderspital, Division of Metabolism, University Children’s HospitaSteinwiesstr. 75, 8032 Zurich, Switzerland. Molecula

r testing for a specific metabolic disorder remains the gold standard due to its highspecificity and sensitivity and possibility of accurate prenatal diagnosis. We report four casesof urea cycle defect where mutational analysis of the involved genes was performed andsubsequently, prenatal diagnosis could be offered to one of the family.Citrullinemia, Inborn errors of metabolism, Ornithine transcarbomylasedeficiency.Correspondence to:Prof Madhulika Kabra, Genetic Unit,Department of Pediatrics, All India Instituteof Medical Sciences, New Delhi 110 029,Received: June 11, 2011;Initial review: June 23, 2011;Accepted: November 12, 2011.Newborns with a urea cycle disorder often appear normallethargy, anorexia, hyperventilation or hypoventilation,hypothermia, seizures, abnormal posturing, and coma. Inlife. These hyperammonemic episodes are marked by lossof appetite, cyclic vomiting, lethargy, and behavioralabnormalities. We herein report four cases of varying1: A six-year-old male child presented with centile by NCHS), slurredcerebral atrophy. He had hyperammonemia (levelstherapy. Tandem mass spectroscopy showed high gene waschemistry). It revealed a mutation p.Arg265Cys in ahomozygous state. Unfortunately, the child developed2: A four-day-old female born to aencephalopathy on day three of life. There was history ofon several occasions without significant acidosis. Hermedications (Sodium benzoate) and peritoneal dialysis.Subsequently, child was lost to follow up but her DNA gene showed the mutationp.Arg157His in a homozygous state with both parents3: Another four day-old female child, a product of