Hematopoietic Stem Cell Transplantation for Patients with Autosomal Recessive Complete INF-λ Receptor 2 Deficiency: Experience in Oman.

Autosomal recessive complete INF-γ receptor-2 (IFN-γR2) deficiency is a rare, potentially fatal primary immune deficiency that predisposes to disseminated mycobacterial disease. Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment. Few patients have been reported so far. Here we report the outcomes of HSCT in 7 patients with IFNγ-R2 deficiency from 3 Omani families who underwent HSCT at Sultan Qaboos University Hospital in Oman. All patients were homozygous for the same mutation (c.-175_+102del) of INFGR2. Four patients underwent HLA-matched related donor (MRD) HSCT (3 siblings and 1 parent), and the other 3 underwent T cell-depleted (TCD) haploidentical HSCT from a family donor. The stem cell source was peripheral blood stem cells in 5 patients and bone marrow in 2 patients. Five patients received myeloablative conditioning, and 2 had reduced-intensity conditioning. The overall survival rate was 85.7%, and the event-free survival was 71.4%. One of the 7 patients died on day +31 with gram-negative sepsis, and the other 6 patients were cured from their original disease (median follow-up of 78.5 months). One patient had primary graft failure following a TCD-haploidentical transplantation and underwent successful retransplantation from another haploidentical relative. Three patients received a donor lymphocyte infusion for mixed chimerism. Our findings indicate that HSCT is curative for complete IFN-γR2 deficiency. In this cohort from Oman, 85.7% of the patients were cured with either an MRD or a TCD haploidentical transplantation. Genetic analysis at birth in children of high-risk couples permits early diagnosis, prevents the morbidity of BCG vaccination, and can enable safer and more successful transplantation outcomes.

A child with phenylketonuria and focal segmental glomerulosclerosis, the bright side of proteinuria.

Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism. Phenylalanine hydroxylase is the underlying deficient enzyme. If left untreated, growth failure, microcephaly, global developmental delay, seizures and severe intellectual impairment would characterize the clinical picture of PKU. On the other side of protein homeostasis lies nephrotic syndrome. It is a well-known quantitative defect due to significant proteinuria. Focal segmental glomerulosclerosis (FSGS) is a special congenital variant affecting children and adults. Hereby, we describe a three- year old male child who presented with generalized edema and global developmental delay. Investigations revealed PKU along with FSGS. We assume that congenital nephrosis ameliorated the picture of PKU, and had a salutary effect on the growth and development. Such coexistence between PKU and FSGS hasn't been described before.

Incidence of antibiotics resistance among uropathogens in Omani children presenting with a single episode of urinary tract infection.

Urinary tract infection (UTI) is one of the most common community-acquired infections. Different organisms can be the cause of UTI in children, with resistance to antibiotics becoming a significant problem in the choice of treatment. Worldwide studies have documented the prevalence of uropathogens in different countries. However, there is no previous study documenting the incidence of different uropathogens in Oman. We aim to report the most common uropathogens and their antibiotic sensitivity patterns in children presenting with documented, single episode UTI at a tertiary hospital in Oman. A retrospective analysis of all Omani children below 14 years who presented with a case of first documented UTI to SQUH between September 2008 and August 2012 was conducted. Data were obtained from the patients' electronic records in the hospital information system. Data were then analyzed using SSPS (Statistical Package for Social Sciences program, Version 20, IBM, Chicago, IL, USA). In the retrospective review of all urine cultures, 438 positive urine cultures were identified. Out of those, 208 (47.5%) belonged to children with their first episode of UTI. Thirty-three patients were excluded and 75 patients were included in the final analysis. Escherichia coli was the most frequently encountered uropathogen in our cohort (69%), followed by Klebsiella pneumoniae infection (17%). Nearly half (46.6%) of these two common organism were resistant to Cotrimoxazole, while 31% of them were resistant to Augmentin. Twenty-four percent of the E. coli and K. pneumoniae strains were resistant to Cefuroxime, and only 10% were resistant to nitrofurantoin. Both Augmentin and Cotrimoxazole should not be the first line antibiotics to treat UTI.

Successful management of a neglected case of nephropathic cystinosis.

Cystinosis is a rare metabolic disorder characterised by lysosomal cystine accumulation leading to multi-organ damage; clinically, the kidneys are the first organ affected. Respiratory insufficiency caused by overall respiratory muscle myopathy is a life-threatening complication. Treatment with cysteamine should be initiated rapidly and continued lifelong to prolong renal function and protect the extra-renal organs. We report the case of a four-year-old Omani girl, diagnosed with infantile nephropathic cystinosis at 21 months. Cysteamine was prescribed but with no compliance to medications. She presented to the Child Health Department of Sultan Qaboos University Hospital, Oman, two years later with severe failure to thrive, electrolyte disturbance and respiratory failure. The hypoventilation and early respiratory dysfunction, due to intercostal and diaphragm myopathy, was treated by non-invasive positive-pressure ventilation. The patient was discharged after four months of intensive rehabilitation with no ventilator support. No standard treatment options have yet been established for respiratory dysfunction in cystinosis.

Primary immunodeficiency diseases in oman: five years' experience at sultan qaboos university hospital.

BACKGROUND: Primary immunodeficiency diseases (PIDs) are considered rare but are generally assumed to be more common in Middle Eastern countries. The prevalence and characteristics of PIDs are unknown in Oman. METHODS: Sultan Qaboos University Hospital is the national referral center for PID in Oman during the study period. Patients were diagnosed and classified according to the clinical and laboratory criteria of PID reported by the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee. A registry was created, and patient data were analyzed between July 2005 and July 2010. RESULTS: Over a 5-year period, there were a total of 90 patients, with an estimated prevalence of 4.5 cases per 100,000. The most common form of immunodeficiency was phagocyte disorders (42%), mainly chronic granulomatous disease, followed by predominantly antibody disorders (18%), other well-defined PID syndromes (13%), and combined immunodeficiencies (12%). The median age of onset of symptoms was 9 months. The median age of diagnosis was 24 months. Consanguinity was present in 81% of patients. The most common infectious presentation was pneumonia (42%), followed by deep abscess (27%) and BCGosis (12%). A total of 25% of patients required intravenous immunoglobulins treatment, 4% required gamma interferon therapy, and 11% underwent bone marrow transplantation. Of all PID patients, 90% survived treatment, whereas 10% did not. CONCLUSIONS: The estimated minimum prevalence of PID in Oman is 4.5 cases per 100,000, with a predominance of phagocyte disorders. Consanguinity is a significant factor; pneumonia and deep abscesses were the main infectious presentations. The overall survival rate was 90%. Strategies are needed to improve the care for PID patients and to increase the awareness among parents and physicians.

dRTA and hemolytic anemia: first detailed description of SLC4A1 A858D mutation in homozygous state.

Mutations in the anion exchanger 1 (AE1) gene encoding the erythroid and kidney anion (chloride-bicarbonate) exchanger 1 may result in familial distal renal tubular acidosis (dRTA) in association with membrane defect hemolytic anemia. Seven children presenting with hyperchloremic normal anion gap metabolic acidosis, failure to thrive, and compensated hemolytic anemia were studied. Analysis of red cell AE1/Band 3 surface expression by Eosin 5'-maleimide (E5M) was performed in patients and their family members using flow cytometry. Genetic studies showed that all patients carried a common SLC4A1 mutation, c.2573C>A; p.Ala858Asp in exon 19, found as homozygous (A858D/A858D) mutation in the patients and heterozygous (A858D/N) in the parents. Analysis by flowcytometry revealed a single uniform fluorescence peak, with the mean channel fluorescence (MCF) markedly reduced in cases with homozygous mutation, along with a left shift of fluorescence signal but was only mildly reduced in the heterozygous state. Red cell morphology showed striking acanthocytosis in the homozygous state [patients] and only a mild acanthocytosis in heterozygous state [parents]. In conclusion, this is the first description of a series of homozygous cases with the A858D mutation. The E5M flowcytometry test is specific for reduction in the Band 3 membrane protein and was useful in conjunction with a careful morphological examination of peripheral blood smears in our patient cohort.

Shaken baby syndrome as a form of abusive head trauma.

Shaken baby syndrome (SBS) is a form of abuse that is characterised by brain injury. Because of the subtle and yet debilitating neurobehavioural impairment which ensues, SBS represents a diagnostic dilemma for attending clinicians. The situation is made worse by the young age of the affected child who may not be capable of explaining what happened. SBS has been reported in many parts of the world. To our knowledge, there is a dearth of literature on the topic from Arab/Islamic countries. This article attempts to shed light on the syndrome by reviewing information on the aetiology of SBS, as well as on its diagnosis and the reasons for delayed diagnosis. The central aim of this review is to increase awareness of SBS so that enlightened policies for prevention and intervention could be developed in the region and particularly in Oman.

Omenn's Syndrome: A rare primary immunodeficiency disorder.

Over the last 17 years different forms of severe combined immunodeficiency have been diagnosed at Sultan Qaboos University Hospital, Muscat. Omenn's syndrome is a rare autosomal recessive form of severe combined immunodeficiency. We report a 6 weeks old Omani infant who presented with the characteristic clinical and immunological phenotype of Omenn's syndrome. We take the opportunity to discuss and review the immunological aspect of this rare syndrome.