Skin prick test reactivity to common aero and food allergens among children with allergy

Background: The prevalence of allergic diseases has risen in the last decades. The objective of this study was to determine the common allergens in children via the skin prick test

Methods: This cross-sectional study recruited 313 allergic children [4 months to 18 years old] referred to the Asthma and Allergy Clinic of Children's Medical Center in Tehran. A questionnaire containing demographic data and patient history was completed. The Skin Prick Test [SPT] was selected according to the patients' history of food and/or aeroallergen sensitivity

Results: Patients [62.4% male, 37.6% female] with symptoms of asthma [n=141, 57.1%], allergic rhinitis [n=50, 20.4%], atopic dermatitis [n=29, 11.7%], and urticaria [n=20, 8.1%] were studied. Positive skin prick test to at least one allergen was 58.1%. The most prevalent allergens were tree mix [26%], Alternaria alternata [26%], weed mix [23.6%], Dermatophagoides farinae [22.9%], Dermatophagoides pteronyssinus [22.9%], milk [21.7%], eggs [20%], and wheat flour [18.3%]. Also, common allergens in the patients with different symptoms of allergic disorders were as follows: asthma [tree mix, weed mix, and Dermatophagoides farinae]; allergic rhinitis [Dermatophagoides farinae, tree mix, and Dermatophagoides pteronyssinus]; and atopic dermatitis [Alternaria alternata, Dermatophagoides pteronyssinus, and cockroaches]

Conclusion: Identifying allergens in each area is necessary and has an important role in the diagnosis and management of allergic disorders and possibility of performing immunotherapy. In this study, the most common aeroallergens were tree mix, Alternaria alternata, and weed mix and also the most common food allergens were milk, eggs, and wheat. Considering these data, appropriate preventive strategies can decrease the cost and morbidity of therapeutic actions

Comparison between sensitivity of autologous skin serum test and autologous plasma skin test in patients with chronic idiopathic urticaria for detection of antibody against IgE or IgE receptor [FcepsilonRIalpha]

Intradermal injection of autologous serum and plasma elicit a cutaneous reactivity in almost 45-60% of patients with Chronic Idiopathic Urticaria [CIU]. This reactivity is associated with the presence of auto antibodies against IgE or IgE receptors. This study was carried out to compare the cutaneous reactivity of autologous serum and plasma skin tests in a series of patients with CIU for diagnosis of auto antibodies against IgE or IgE receptor. Fifty eight patients with CIU were injected intradermally with autologous serum and plasma [anticoagulated by citrate]. Histamine was used as positive control and normal saline as negative control. The study group was checked by routine laboratory tests [CBC, U/A etc], allergens with skin prick tests, and serum IgE level, and auto antibodies against thyroid as well. Duration of urticaria was another factor which was assessed. There was no significant difference between positive ASST and positive APST patients for the above mentioned tests. 77.6% of the patients were Positive for APST and 65.5% were ASST positive. Duration of urticaria was longer in patients with positive ASST and APST than ASST and APST negative patients, although the difference was not statistically significant. Autologous serum skin test [ASST] and autologous plasma skin test [APST] could be used for estimation of duration and severity of urticaria and planning for the treatment

single center study of clinical and paraclinical aspects in Iranian patients with allergic rhinitis

Allergic rhinitis [AR] is a common form of allergic disorder in Iran and rest of the world. This study was conducted to investigate the symptoms and paraclinical aspects of this allergy among Iranian patients. A total of 206 patients [51.5%: male], with one of the specific symptoms of AR, from March 2005 to March 2007 were enrolled in the study. A written questionnaire was completed for each patient. Furthermore, paraclinical evaluations including CBC, serum total IgE, spirometry and skin prick test [SPT] with common allergens were done for the patients. The ages of our patients ranged from 2 to 62 years of age [mean age of 18 +/- 11.8 years]. Mean age of onset of symptoms was 11.6 +/- 9.9 years. In 82% of cases histories of other allergic diseases were seen in patients or their family members. Rhinorrhea was the most common symptom in our patients [77.9%]. Frequencies of mild persistent, moderate - severe persistent, mild intermittent and moderate -severe intermittent types of AR were 20.5%, 41%, 21% and 17.5%, respectively. Frequencies of positive SPTs in all cases, patients with persistent and intermittent allergic rhinitis were 86.7%, 88.2% and 84.1%, respectively. The most common allergens in positive SPTs, were trees, weeds, grasses and Dermatophagoides pteronysinus. About 55.5% of patients showed elevated total IgE levels [>/= 100 IU/ML]. Abnormal spirometry results were seen in 33.5% of cases. The present study showed that among paraclinical investigations for AR, positive SPTs with aeroallergens, are more consistent with clinical findings. Regarding high ferequency of abnormal spirometry, we recommend that clinical suspicion about hyperreactive airway disease in AR patients is mandatory and performing spirometry for these cases is necessary whenever possible

Association of HLA class II alleles with childhood asthma and total IgE levels

Asthma is a complex and multifactorial disorder. Several studies have reported association between different HLA- DQB1 and HLA- DRB1 alleles and allergic asthma. The aim of the present study was to investigate the association of HLA-class II alleles and haplotypes, with total serum IgE and the results of the skin prick test in Iranian children with allergic asthma. A total of 112 patients with allergic asthma symptoms [75 males and 37 females] were selected randomly from the pediatric hospital. In some patients total serum IgE and prick test were determined. Data of this study shows that HLA-DRB1*12 significantly increased in asthmatic patients [4.5% vs. 0%, P-value=0.04]. HLA-DQB1*0603 and 0604 alleles were significantly higher in asthmatics than those in normal controls [10% vs. 0%, P-value= 0.0001; and 9.3% vs. 3.7%, P-value= 0.04, respectively]. The statistical significance was relinquished after p value correction for all alleles except for HLA-DQB1*0602 [Pc=0.03] and HLA-DQB1*0603 [Pc=0.0015]. Conversely, HLA-DQB1*0501 and 0602 were decreased in asthmatics compared to normal controls [7.5% vs. 13.5%, P-value= 0.05; and 4% vs. 12.5%, P-value= 0.002, respectively]. The mean of total IgE in patients was 483 IU, and it was significantly high about 1140 IU in asthmatic patients with positive skin prick test to house dust. The most frequent alleles in asthmatic patients with the total IgE>200 IU/mL were HLA-DRB1*11and 1401, HLA-DQA1*0505, HLA-DQB1*0301 and in patients with total IgE<200 IU/mL were HLA-DRB1*0301, 07 and 1301, HLADQA1*0201 and 0301, HLA-DQB1*0201. These data suggests that HLA-DRB1, DQA1 and DQB1 alleles and haplotypes might be implicated in susceptibility to allergy and asthma and serum IgE production. As asthma and atopy are multifactorial disorders, probably HLA genes are involved in the regulation of immune specific responses to common allergen

Systemic and local reactions of bee venom immunotherapy in Iran

Severe allergic reactions during specific immunotherapy may occur in the treatment of hymenoptera sting allergy. The objective of the present study was to examine the characteristics of allergic reactions during specific immunotherapy in patients with allergy towards hymenoptera venom in the Iranian population. A prospective study was performed using the clinical reports of 27 patients with anaphylaxis to bee venom [Apis melifera, Geupes vespula and Geupes Polites]. Ten patients treated with Cluster protocol during 2002 and 2006 After diagnosis of hymenoptera sting allergy according to history and intradermal tests, the patient were treated with Cluster protocol immunotherapy. The protocol lasted 6 weeks with an increase in the concentration of venom from 0.01? g/ml to 100 ? g/ml. None of the patient received premedication. All patients with hymenoptera venom allergy received 120 injections. Anaphylactic reactions were classified according to the Mueller-classification. The frequencies of systemic reactions during Cluster protocol were 8.33% and 5% for yellow jacket and honey bee venom respectively. No patient experienced severe systemic reaction. Cluster protocol for hymenoptera immunotherapy is a reliable method for the treatment of anaphylactic reactions to bee venom. It is safe with low cost and do not need hospitalization

DNA banking of primary immunodeficiency disorders in Iran

Primary immunodeficiency disorders are a heterogeneous group of genetic disorders, with different modes of inheritance, consisting of more than 100 different types. We constructed the DNA banking of primary immunodeficiency disorders for the first time in Iran. The DNA of 31 immunodeficient patients and their families [total of 92 samples] were collected, as the first step for construction of DNA banking. DNA was isolated from whole blood by salting out method. Among our patients, Common variable immunodeficiency was the most common disorder, followed by X-linked agammaglobulinemia, Ataxia-telangiectasia, Chronic granulomatous disease, Severe combined immunodeficiency, Hyper IgM syndromes, and Leukocyte adhesion defects. DNA banking is a useful method for further detection of mutation in immunodeficient patients and prenatal diagnosis for presence or absence of the disorder in the fetus which can be confirmed by molecular genetics testing

Health-related quality of life in primary immune deficient patients

The primary immunodeficiency [PI] disorders are abnormalities in development and maturation of the immune system. Individuals with PI disease may experience frequent infections, which limit their abilities to exhibit physical and psychological well-being secondary to their illness. In this survey we compared health-related quality of life of primary immune deficient patients with healthy children. The case-control study was designed for patients with PI disease who were referred to Children Medical Center in 2004-2005. Demographic information was taken and Pediatric Quality Of Life [PEDQOL] questionnaire were filled for 50 PI patients and 100 healthy children. The mean age in PI patients was 12.62 +/- 3.65 [range from 8 to 18] years and in the control group was 11.04 +/- 3.3 years. In PI patients 68% were male and 32% female .Most patients with PI disease had a diagnosis of common variable immunodeficiency [54%] or X-linked agammaglobulinemia [24%]. Patients with PI disease had great limitations in physical functioning and psychological well-being [p<0.001 and p<0.001 respectively] compared with children without a chronic health condition. Patients had lower PEDQOL scores in all age groups compared with normal sample [p<0.001]. Long duration of disease significantly correlated with low psychological score. [r=-3.23. P=0.03] Children with PI disease experience poorer health related quality of life than healthy children, indicating more attention should be paid to early diagnosis and treatment of PI disease, as well as more attention to their social limitation. PI patients may need psychological consultation for better coping with their illness

Study of alpha1-antitrypsin phenotypes frequencies in patients with primary antibody deficiency

Primary antibody deficiencies are the most frequent primary immunodeficiency disorders. Bronchiectasis as a feature of these disorders may be developed due to some factors such alpha-1-antitrypsin deficiency. In order to determine the prevalence of two common alpha-1-antitrypsin deficiency alleles [PI*Z and PI*S] in Iranian patients with antibody deficiency, this study was performed. The prevalence of PI*M, PI*S, and PI*Z allele combinations was determined in 40 patients with primary antibody deficiency [with and without bronchiectasis] and compared with 60 healthy control subjects. Phenotyping was performed by isoelectric focusing. The phenotype frequencies among patients were as follow: M in 92.5%, S in 2.5% and Z in 5%. There was not any significant difference in distribution of alleles or phenotypes between patients and control subjects. Moreover, no significant difference was found between patients with and without bronchiectasis. We did not find evidence to support an association between alpha-1-antitrypsin phenotypes and primary antibody deficiencies in a small, controlled study. Larger studies will be required to clarify the relationship between alpha-1-antitrypsin genotype and susceptibility to bronchiectasis in patients with antibody deficiency

Assessment of quality of life in Iranian asthmatic children, young adults and their caregivers

Interest in the impact of illness on day to day function is leading investigators to include both disease specific and generic health related quality of life [HR QOL] questionnaires in a broad range of clinical studies and to gain a full picture of the impact of asthma on the lives of children with this condition, it is necessary to make direct measurement of health related quality of life. In response to this need, we used the Juniper's pediatric asthma quality of life questionnaire [PAQLQ] and Juniper's Pediatric Asthma Caregiver's Quality of Life Questionnaire [PACQLQ] that has been developed based on guidelines for construction of over a dozen validated disease specific quality of life instruments. The PAQLQ consists of 23 items that in children with asthma have been identified as troublesome in their daily lives and PACQLQ that contains 13 items in two domains of emotional and activities disturbances. The study design consisted of an 18 month single cohort study. Patients participating in the study were 113 children, 7-17 years of age, with a wide range of asthma severity and their caregivers. For each patient a PAQLQ and for each caregiver a PACQLQ was completed. One week before visit patients recorded morning peak flow rates, medication use and symptoms in a diary. After complete physical examination, for determining of asthma severity, spirometry was performed. The questionnaires after statically analysis showed good levels of both longitudinal and cross sectional correlations with the conventional asthma indices and with general quality of life. We found that consistently QOL in boys were more disturbed than females, a good relevancy between severity of asthma and QOL scores and more disturbances of QOL in caregivers of male asthmatic patients than caregivers of female asthmatic patients. We could not find any significant relevancy between FEV1 percentage of predicted and overall scores of QOL. Smaller airways, and higher airway resistance and more activity of males than females may explain why boys have more disturbed life style than females

Total serum igE and skin tests in children with respiratory allergy

Total serum IgE measurement and skin prick tests are the most common tools for allergy diagnosis. This investigation was conducted to evaluate total serum IgE and skin prick test relationship in Iranian atopic children with respiratory manifestations. A history of allergic rhinitis, bronchial asthma and atopic dermatitis was obtained in 232 children [aged 1 to 15 years]. Skin prick testing was performed using commercial preparation of the common allergens. The patients'sera were also analyzed for determining total IgE. More than 95% [n=221] of the patients had positive skin prick test [mean wheal diameter > /=3mm] to one allergen or more. Among the patients 46% [n=107] had elevated total serum IgE levels [> /=150 IU/ml]. The study showed close relationship of skin test positivity with reported allergic symptoms, but no correlation was found between total IgE and skin prick test. This study revealed that skin testing and total serum IgE measurement may be considered complementary to one another in diagnosing allergic respiratory disorders

High doses intravenous immunoglobulin versus oral cyclosporine in the treatment of severe atopic dermatitis

Atopic dermatitis is one of the most common allergic diseases that almost always respond to conventional therapies with topical emollient, topical corticosteroids, systemic antihistamines and allergic abstinence. However few cases of atopic dermatitis with severe course do not respond to conventional therapies and high dose of intravenous immunoglobulin or cyclosporine are recommended for them. This clinical trial study has been done to compare the last two regimens in patients with severe atopic dermatitis, Scoring Atopic Dermatitis [SCORAD] > 70. We included 14 patients in two groups. In group 1, eight patients were randomly selected and received 4mg/kg cyclosporine daily for 3 months and in group 2, six patients received 2g/kg Intravenous Immunoglobulin [IVIG] as stat infusion. All patients were followed on days 15, 30, 60 and 90 after starting the therapy. About 75% and 62.5% of patients had positive skin tests to egg and to milk respectively. Six patients out of 14 patients did not have skin test, so specific IgE by Radioallergosobent tests [RAST] was used for them. All of these patients had positive RAST to egg and 66.6% against cow's milk. There was a significant difference in the clinical outcomes of these two groups with a marked reduction in SCORAD of day 90[th] in group 1 in comparison to group 2 [Pvalue = 0.005]. No significant adverse drug reaction was seen in these two groups

Chronic mucocutaneous candidiasis; report of three cases with different phenotypes

Chronic Mucocutaneous Candidiasis [CMCC] refers to a group of immunodeficiencies, characterized by persistent or recurrent infections of the skin, nails, and mucus membranes caused by candida. A wide range of immunologic abnormality has been reported in CMCC. Defects in cellular limb of the immune system, mainly the specific response to antigens of candida species, are well documented in CMCC patients. A subgroup of patients is predisposed to development of autoimmune endocrinopathies. These patients need repeated monitoring of endocrine functions. Immunologic studies are needed to identify the extent of immunodeficiency and other abnormalities of immune functions. We report three cases of CMCC. These patients show different phenotypes and highlight the need for complete evaluation and long term follow-up for accompanying disorders

Comparison between peak expiratory flow rate and forced expiratory volume in one second in the evaluation of children suspected to have asthma

This study was conducted to evaluate whether forced expiratory volume in 1 second FEV[1] for the diagnosis of bronchial reactivity by means of the free-running exercise test and bronchodilator inhalation, could be appropriately replaced by simple measurements of peak expiratory flow rate [PEFR] in children. We studied 108 referred symptomatic children [due to chronic cough or wheezing] suspected to have asthma aged 5-14y. Forced breathing spirometry and the [Mini-Wright peak flow meter] tests were recorded before and fifteen minutes after the challenge with free- running exercise or bronchodilator [Salbutamol] inhalation, regarding the baseline FEV[1] value [FEV[1]> 80% considered as normal]. There was a high correlation between PEFR and FEV[1] [in absolute value and percent predicted] measured before and after bronchodilator inhalation test [r = 0.48, P = 0.05] in comparison to the values referred to free- running exercise test [r = 0.26, P = 0.01]. [forced breathing spirometry] and [Mini-Wright peak flow] cannot be used interchangeably for diagnosing asthma, and PEFR measurement should remain a procedure for monitoring and following up the patients

Mortality in primary immunodeficient patients, registered in Iranian primary immunodeficiency registry

Primary immunodeficiencies [PID] are a group of disorders, characterized by an unusual susceptibility to infections. Delay in diagnosis results in increased morbidity and mortality in affected patients. The purpose of this study was to determine the mortality rate of Iranian immunodeficient patients referred to Children Medical Center Hospital affiliated to Tehran University of Medical Sciences over a period of 20 years. In this study, records of 235 [146 males, 89 females] patients with immunodeficiency who were diagnosed and followed in our center, during 22 years period [1979 2001] were reviewed. The diagnosis of immunodeficiency was based on the standard criteria. The cause of death was determined by review of death certificates. Antibody deficiency was the most common diagnosis made in our patients. The overall five-year survival rate was 22.7% in our studied patient group; this was greatest in antibody deficiency. During the 22 year period of study, 32 patients died. As some of the patients could not be located, the true mortality rate ranged between 13.6% and 17.5%. The main leading cause of death were lower respiratory tract involvement in 14 cases [44%]. The most common pathogenic microorganisms causing fatal infections were psudomonas and staphylococcus in 9 cases [28.1%] followed by E. coli in 7 [21.9%], tuberculosis in 13 [40.6%] and salmonella in 1 [3.1%]. Based on our study, delay in diagnosis in patients with PID results in tissue and organ damage and several complications. Mortality and morbidity are increased in undiagnosed patients

Clinical and laboratory findings in Iranian children with cyclic neutropenia

Cyclic neutropenia is a rare immunodeficiency syndrome, characterized by regular periodic oscillations in the circulating neutrophil count from normal to neutropenic levels through 3 weeks period, and lasting for 3-6 days. In order to determine the clinical features of cyclic neutropenia, this study was performed. Seven patients with cyclic neutropenia [3 males and 4 females], who experienced neutropenic periods every 3 weeks [5 with severe and 2 with moderate neutropenia], were investigated in this study. They had been referred to Iranian Primary Immunodeficiency Registry during 23 years [1980-2003]. The range of patients' ages was from 7 to 13 years [median 11 years]. The median age at the onset of the disease was 12 months [1 month- 2 years] and the median age of diagnosis was 2 [1.5-5] years, with a median diagnosis delay of 1 year [2 months- 5 years]. Neutropenia was associated with leukopenia [3 patients], anemia [3 patients], and thrombocytopenia [1 patient]. Patients were asymptomatic in healthy phase, but during the episode of neutropenia suffered from aphthous ulcers, abscesses and overwhelming infections. The most commonly occurred manifestations were: otitis media [6 cases], oral ulcers [5 cases], abscesses [4 cases], pneumonia [3 cases], diarrhea [3 cases], oral candidiasis [3 cases], cutaneous infections [2 cases], and periodontitis [2 cases]. One of these patients subsequently died because of recurrent infections. Unusual, persistent or severe infections should be the initiating factors to search for an immune deficiency syndrome such as cyclic neutropenia, because a delay in diagnosis may result in chronic infection, irretrievable end-organ damage or even death of the patient

Neutropenia in patients with primary antibody deficiency disorders

Neutropenia is characterized by decrease in the absolute number of circulating neutrophils and an increase susceptibility to infections. The current study was performed in order to explain the clinical and laboratory findings of patients with antibody deficiency disorders associated neutropenia. The patients' records of 19 neutropenic cases out of 207 patients with antibody deficiencies, who had been referred to Children's Medical Center and enrolled in Iranian primary immunodeficiency registry, were reviewed. Nineteen cases [14 male and 5 female], with a mean age of 10.7 +/- 5.7 years, were associated with neutropenia [9.2%]. The disorders with associated neutropenia were Hyper IgM syndromes [3 of 8], Common variable immunodeficiency [13 of 109], and X-linked agammaglobulinemia [3 of 45]. The median age for the onset of disease and diagnosis age were 15 months [1-134] and 3.8 years [6 months-13 years], respectively. The most common infections during the course of illness were pneumonia [13 cases], diarrhea [12 cases], oral candidiasis [9 cases], otitis media [6 cases], sinusitis [6 cases], cutaneous infections [5 cases], and abscess [5 cases]. Other less frequent infections were: conjunctivitis, oral ulcers, meningitis, and osteomyelitis. Three neutropenic patients died because of recurrent infections. Neutropenia may occur in any of the primary immunodeficiency disorders. Persistent or severe infections always pose a supposition, which deserves further evaluation for detecting an underlying immune deficiency syndrome and neutropenia, since a delay in diagnosis may result in a serious organ damage or even death of the patient

Gastrointestinal manifestations of patients with Chronic Granulomatous Disease

Chronic Granulomatous Disease [CGD] represents a group of inherited disorders of phagocytic system, manifesting recurrent infections at different sites. The present study was accomplished in order to determine the gastrointestinal manifestations of CGD patients. Fifty-seven patients [38 males and 19 females] with CGD, who had been referred to three immunodeficiency referral centers in Iran, were studied during a 24-year period [1980-2004]. The median age at the time of study was 14.5 years old [1-56 years]. The median onset age of symptoms was 5 months [1 month - 13.75 years], and that of diagnostic age was 5 years [2 months- 54.1 years], with a diagnostic delay of 33 months, on average. Seven patients were presented with acute diarrhea, 3 with oral candidiasis, and 2 with liver abscesses as the first chief complaints. Twenty-four cases [42.1%] had been complicated by gastrointestinal manifestations during their course of the disease. Of those, 12 cases [21.1%] had diarrhea, 7 [12.3%] oral candidiasis, 5 [8.8%] hepatitis, 4 [7.0%] hepatic abscess, and 2 cases [3.5%] gastric outlet obstruction. Also, failure to thrive was detected in 6 patients [10.5%]. Four patients died [7%]. CGD should be excluded in any patient with gastrointestinal manifestations especially chronic diarrhea, hepatic abscess, and gastric outlet obstruction

Screening of the Bruton tyrosine kinase [BTK] gene mutations in 13 Iranian patients with presumed x-linked agammaglobulinemia

X-linked agammaglobulinemia [XLA] is an immunodeficiency caused by mutations in the Bruton tyrosine kinase [Btk] gene. In order to identify the mutations in Btk gene in Iranian patients with antibody deficiency, 13 male patients with an XLA phenotype from 11 unrelated families were enrolled as the subjects of investigation for Btk mutation analysis using PCR-SSCP followed by sequencing. Five different mutations were identified in 5 patients from 5 unrelated families. Three mutations had been reported previously including TTTG deletion in intron 15 [4 bps upstream of exon 16 boundary], nonsense point mutation [1896G>A] that resulted in a premature stop codon [W588X] in kinase domain, and nucleotide alteration in invariant splice donor site of exon12 [IVS12+1G>A]. While 2 novel missense mutations [2084A>G, 1783T>C] were identified leading to amino acid changes [I651T, Y551H]. The results of this study further support the notion that molecular genetic testing represents an important tool for definitive and early diagnosis of XLA and may allow accurate carrier detection and prenatal diagnosis

Report of six cases of Chediak-Higashi syndrome with regard to clinical and laboratory findings

Chediak Higashi Syndrome [CHS] is a rare, primary immunodeficiency disorder with an autosomal recessive [AR] inheritance and characterized by recurrent infection, partial occulocutaneous albinism and an accelerated phase. In this report we describe clinical and laboratory findings from 6 CHS patients. Clinical and laboratory information of six patients who were referred to our center during the last 20 years [from 1983 - 2003] were reviewed. Onset age of disease was between 3 months to 10 years. All patients had history of consanguineous parents and two patients were siblings. All patients had oculocutaneous albinism, nystagmus, recurrent infections which included upper and lower respiratory tract [U and LRT] infections, stomatitis, thrush, and skin abscesses and hepatitis. In laboratory findings, all patients had neutropenia and normal immunoglobulins and normal CD3, CD4, and CD8, CD19 Lymphocyte by flowcytometry and three of the four patients had chemotatic defect. Five patients certainly had giant granule in bone marrow neutrophil and in one patient it was equiovocal. Three patients had an accelerated phase, and for one patient bone marrow transplantation was done that was tolerated well and had been well after 7 years. We emphasize the need for early diagnosis on basis of characteristic facies and diagnostic laboratory examinations and early bone marrow transplantation [BMT] in patients