Case Report
Volume 1 Issue 1 - 2015
Hyper Immunoglobulinemia D syndrome in a Saudi girl: A Case Report
Rola Sleiman*
Department of Paediatrics, Fakeeh Hospital, Saudi Arabia
*Corresponding Author: Rola Sleiman, Department of Paediatrics, Fakeeh Hospital, Palestin street, Jeddah, Saudi Arabia.
Received: December 15, 2014; Published: January 31, 2015
Citation: Rola Sleiman. “Hyper Immunoglobulinemia D syndrome in a Saudi girl: A Case Report”. EC Paediatrics 1.1 (2015): 8-10.
Abstract
An eight years Saudi girl from consanguineous parents died after long history of mysterious febrile disease diagnosed and treated as Familial Mediterranean fever. Genetic studies showed double homozygous mutation V377I which is characteristic of hyper immunoglobulin-D syndrome (HIDS). This is the first reported case of hyper immunoglobulin-D from Saudi kingdom.
Keywords: Hyperimmunoglobulinemia D syndrome; Periodic fever; Saudi girl
Abbreviations: HIDS: Hyperimmunoglobulinemia D Syndrome; MK: Mevalonate Kinase; CRP: C Reactive Protein; KSA: Kingdom of Saudi Arabia; FMF: Familial Mediterranean fever
Introduction
Hyper Immunoglobulinemia-D syndrome (HIDS) was first described in 1984 by Van Deer Mer in patients with periodic fever and Dutch ancestry and named auto inflammatory disease not autoimmune diseases because of the absence of antibodies [1,2].
HIDS is a rare autosomal recessive disease. It is caused by an inborn error of cholesterol biosynthesis brought about by a gene mutation (MVK), controlling an enzyme called mevalonate kinase (MK) located on chromosome 12q24 [3]. More than 60 mutations have been reported but more frequent are V377I and I268T [4]. These mutations causes variable degrees of deficiency of mevalonate kinase (MK) which will lead to a defects in the production of isopronoids and steroids resulting in bouts of inflammation that involve many organs mainly gastrointestinal, musculoskeletal and the skin. clinical features include severe diarrhoea, arthralgia, rash and mouth ulcers and Laboratory features include an acute phase response (elevated CRP and ESR) and markedly elevated IgD (and often IgA), although cases with normal IgD have been described. Most cases are reported in the Northern countries in the west are perhaps causes by founder effect. Herein, we report a second HIDS case in a female Saudi girl from the Arab world.
Case Report
An 8 year-old Saudi girl has been frequently admitted to hospital since the age of 1 year because of recurrent attacks of fever that lasted for about one week. The attacks were preceded by malaise, rigors and chills which were accompanied by gastrointestinal manifestations mainly vomiting, abdominal pain and watery diarrhea leading to severe dehydration. Over the years she developed also symmetrical arthritis of the large joints. By the age of six years, she started to use a wheelchair during her attacks due to her severe knees arthritis. She had a generalized maculopapular rash, acute myositis, vertigo and severe headache, ataxia and febrile seizures.
She had many hospital admissions during the year between 2006 and 2012, during her attacks she was miserable and became very sick. Antibiotics were prescribed each time because of high fever, CRP and ESR but were ineffective most of the times. In the last two years other therapies as colchicine, corticotherapy and parenteral hydration were given, and were more effective.
She often needed blood transfusions for severe microcytic hypochromic anemia which didn’t respond to iron therapy. Laboratory findings showed an acute phase response of leucocytosis of 30000, C reactive protein 400 and ESR 120. Complete recovery and normalization of these critical values between attacks took 4 to 12 weeks. Renal, hepatic and cardiovascular examinations were completely normal.
Infectious causes as primary immunodeficiency, autoimmune diseases and neoplastic syndromes have been checked for and were excluded during the course of the disease over the years. Immunoglobulin subclass IgG 4 was found to be low in one occasion. This finding couldn’t explain the symptomalogy of this child. The rest if IgG subclass were in the normal range measured many times, IgA, IgM, IgE levels were normal and IgD level was not measured.
Imaging studies showed a splenomegaly with swollen mesenteric lymph nodes during attacks whereas the bone marrow aspiration and biopsy, electroencephalogram EEGs and the brain imaging were all normal. Upper and lower endoscopies with biopsies were all normal also.
By the age of 6 year colchicines therapy was given and her attacks became less frequent and less severe, but this medication was discontinued when genetic studies for Familial Mediterranean fever were negative. However this therapy was resumed due to its beneficial effects on the child's health. A short course of intravenous corticotherapy during the attacks was very successful and the fever resolved in less than 48 hours (1 mg/kg/day of methylprednisolone for five days). Sometimes prednisolone syrup at 1 mg/kg/day was given for duration of one week when fever and vomiting began which ameliorate the patient and avoided the patient admission to hospital.
After the age of eight years she had her last febrile attack was complicated by severe status epilepticous and multi-organ failure which leads to her death [5]. Finally an Extensive genomic study on periodic fever was done in a highly specialized laboratory showed a homozygous mutation V377I. Blood samples were sent to the national human genome research institute to look for possible mutations that could explain the disease other than FMF mutations because genetic studies for FMF were negative. Unfortunately the results came soon after patient death.
Discussion
This is the first case of HIDS from kingdom Saudi Arabia (KSA), and second reported case from Arab world, First case was reported by doctor Hammoudah from Palestine in 2004 [6]. A recent review of 50 patients from Europe show that many cases of HIDS occur in people of Arabic ethnicity [7]. The rarity of this disease was due to delay in diagnosis, since most cases of periodic fever were considered to be Familial Mediterranean Fever (FMF) which are prevalent and known in KSA [8]. The clinical presentation of our patient was similar to that described in the literature by the irregularity of fever attacks [9]. There was no evidence that the onset of attacks was related to a vaccine, trauma or stress [10]. A sub group of HIDS patients can develop neurological manifestations of variable degrees such mental retardation, ataxia and ocular symptoms.
These findings can be related to a continuum spectrum between the mevalonic aciduria (severe form of mevalonate kinase deficiency) and HIDS (partial form of mevalonate kinase deficiency) [11]. Our patient had febrile convulsions. She had also severe vertigo which leads to inability to stand or walk during attacks. Our patient had normal immune profile except for low IgG 4 and this was reported by one study [12]. The treatment of HIDS patients using colchicines is controversial; most data showed no benefits although a few cases did show improvement as occurred for in our patient [13]. There are other treatments as etanercep, TNF-alpha inhibitor, anakinra, IL-1 receptor antagonist but none were tried in our patient. Similar results have been found for intravenous corticoid given for short periods during the attacks [14]. The genetic studies show that a V377I mutation is present almost in 80% of HIDS cases [15].
Conclusion
The diagnosis of hyper IgD syndrome for the first time in Saudi Kingdom should raise the awareness of the importance of genetic study in any patient with periodic fever. More of research is needed for treatment of HIDS to avoid severe morbidity and mortality related to this disease.
Bibliography
  1. Van Der Meer JW., et al. “Hyperimmunoglobulinaemia D and periodic fever: a new syndrome”. Lancet 1 (1984): 1087-1090.
  2. Samuels J and Ozen S. “Familial Mediterranean fever and the other auto inflammatory syndromes: evaluation of the patient with recurrent fever”. Current Opinion in Rheumatology 18.1 (2006): 108-117.
  3. Anna Simon., et al. “Molecular Analysis of the Mevalonate Kinase Gene in a Cohort of Patients with the Hyper-IgD and Periodic Fever Syndrome: Its Application as a Diagnostic Tool”. Annals of Internal Medicine 135.5 (2001): 338-343.
  4. Lachmann HJ. “Clinical immunology review series: An approach to the patient with a periodic fever syndrome”. Clinical & Experimental Immunology 165.3 (2011): 301-309.
  5. Joost PH Drenth and Van Der Meer. “Hereditary Periodic Fever”. New England Journal of Medicine 345.24 (2001): 1748-1757.
  6. Hammoudeh M. “Hyperimmunoglobulinemia D syndrome in an Arab child”. Clinical Rheumatology 24.1 (2005): 92-94.
  7. Bader-Meunier B., et al. “Mevalonate kinase deficiency: a survey of 50 patients”. Pediatrics 128.1 (2011): e152-159.
  8. Al-Alami JR, et al. “Familial Mediterranean fever mutation frequencies and carrier rates among a mixed Arabic population”. Saudi Medical Journal 24.10 (2003): 1055-1059.
  9. Kastner DL. “Hereditary periodic fever syndromes”. Hematology American Society of Hematology Education Program (2005): 74-81.
  10. Frenkel J., et al. “Clinical and molecular variability in childhood periodic fever with hyperimmunoglobulinaemia D”. Rheumatology 40.5 (2001): 579-584.
  11. Simon A., et al. “Mevalonate kinase deficiency: Evidence for a phenotypic continuum”. Neurology 62.6 (2004): 994-997.
  12. Yao Q and Furst DE. “Autoinflammatory diseases: an update of clinical and genetic aspects”. Rheumatology 47.7 (2008): 946-951.
  13. Goldfinger S. “The inherited autoinflammatory syndrome: a decade of discovery”. Transaction of theAmerican Clinical and Climatological Association 120 (2009): 413-418.
  14. de Dios Garcia-Diaz J and Alvarez-Blanco MJ. “Glucocorticoids but not NSAID abort attacks in hyper-IgD and periodic fever syndrome”. Journal of Rheumatology 28.4 (2001): 925-926.
  15. Haas D and Hoffmann GF. “Mevalonate kinase deficiencies: from mevalonic aciduria to hyperimmunoglobulinemia D syndrome”. Orphanet Journal of Rare Diseases 1(2006): 13.
Copyright: © 2015 Rola Sleiman. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PubMed Indexed Article


EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005


EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777


EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347


EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478


EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253


EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033


EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992


EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505


EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793


EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211


EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047


EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560


EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318


EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819


EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840


EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344


EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476


EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658


EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489


EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278


EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108


EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571


EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333


EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883


EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001


EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937


EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723


EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726


EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603


EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646


EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616


EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290


EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226


EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812


EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268


News and Events


February Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the February issue of respective journals and can be viewed in the current issue pages.

Submission Deadline for April Issue

Ecronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the March issue of respective journals. Submissions are accepted on/before March 12, 2020.

Certificate of Publication

Ecronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

Ecronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.

Immediate Assistance

The prime motto of this team is to clarify all the queries without any delay or hesitation to avoid the inconvenience. For immediate assistance on your queries please don't hesitate to drop an email to editor@ecronicon.uk