Mohamed El-Naggari

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.

Posterior Reversible Encephalopathy Syndrome in Two Omani Children with Underlying Renal Diseases

Posterior reversible encephalopathy syndrome (PRES) is a neurological condition with a combination of clinical and radiological features. Clinical symptoms include headaches, confusion, seizures, disturbed vision or an altered level of consciousness. Classic magnetic resonance imaging (MRI) findings indicate subcortical and cortical oedema, affecting mainly the posterior cerebral region. We report two paediatric cases of PRES with underlying renal diseases presenting at the Sultan Qaboos University Hospital in Muscat, Oman, in April 2010 and August 2011. The first case was an 11-year-old girl diagnosed with systemic lupus erythematosus and the second was a six-and-a-half-year-old boy on peritoneal dialysis due to multi-drug-resistant nephrotic syndrome. Both patients were hypertensive and treated with blood pressure control medications. No residual neurological dysfunction was noted in the patients at a one-year follow-up and at discharge, respectively. The role of hypertension in paediatric PRES cases, among other important risk factors, is emphasised. Additionally, MRI is an important diagnostic and prognostic tool. Prompt diagnosis and aggressive management is fundamental to preventing permanent neurological damage.

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.

Intravenous immunoglobulin in the treatment of vancomycin-induced toxic epidermal necrolysis.

Toxic epidermal necrolysis (TEN), an uncommon but potentially life-threatening skin reaction, is frequently induced by drugs. The mucocutaneous reaction is characterised by bullous detachment of the epidermis and mucous membranes. We present a 9-month-old male with methylmalonic acidaemia, generalised hypotonia, and global developmental delay. He presented with a 3-day history of fever, cough, shortness of breath, and vomiting. Eruption appeared after 5 days of vancomycin treatment. The eruption involved almost 60% of the total body surface area and both eyes. He was successfully treated with intravenous immunoglobulin (IVIG), antibiotics, and appropriate wound management and made a full recovery with negligible sequelae despite the severity of his disease. Important components of successful treatment include early recognition, intensive care, prompt withdrawal of the causative agent, early administration of IVIG, appropriate fluid resuscitation, and control of infection. IVIG might be beneficial in the treatment of TEN; however, controlled studies are needed to evaluate IVIG compared to other modalities.

Blood Culture Contaminants in a Paediatric Population: Retrospective study from a tertiary hospital in Oman

OBJECTIVES Most children presenting with febrile illness require a blood culture to determine the causative organism as well as its sensitivity to antibiotics. However, false-positive results lead to unnecessary hospitalisations, prescriptions and tests. This study aimed to evaluate the impact of false-positive blood cultures among a paediatric population at a tertiary hospital in Oman. METHODS This retrospective study included all 225 children <13 years old with positive blood cultures who presented to the Sultan Qaboos University Hospital, Muscat, Oman, between July 2011 and December 2013. Blood cultures were reviewed to determine whether they were true-positive or contaminated. RESULTS A total of 344 positive blood cultures were recorded during the study period, of which 185 (53.8%) were true-positive and 159 (46.2%) were contaminated. Most true-positive isolates (26.5%) were coagulase-negative Staphylococcus spp. (CONS) followed by Escherichia coli (9.7%), while the majority of contaminated isolates were CONS (67.9%) followed by Streptococcus spp. (6.9%). Children with contaminated cultures were significantly younger (P <0.001) while those with true-positive cultures required significantly more frequent hospital admissions, longer hospital stays and more frequent antibiotic prescriptions (P <0.001 each). Chronic illness and mortality was significantly more frequent among those with true-positive cultures (P <0.001 and 0.04, respectively). While white blood cell and absolute neutrophil counts were significantly higher in true-positive cultures (P <0.001 each), there was no significant difference in C-reactive protein (CRP) level (P = 0.791). CONCLUSION In this population, CRP level was not an adequate marker to differentiate between true- and false-positive cultures. A dedicated well-trained phlebotomy team for paediatric patients is essential.

Amlodipine: The double edged sword

Amlodipine, a calcium channel blocker became one of the most popular antihypertensive medications used in the paediatric population. This is mainly due to its long half‐life making it easy to use as a single daily dose. Amlodipine is associated with common side effects like flushing, headache and dizziness. The incidence of amlodipine‐related oedema was noted to be lower in the paediatric population compared to adults. We emphasise the importance of monitoring the development of oedema in patients treated with amlodipine.

Henoch‐Schonlein purpura with lupus‐like nephritis: an uncommon occurrence

Dear Editor, A 13-year-old boy presented with severe abdominal pain of 1 week’s duration. Examination revealed generalized abdominal tenderness with guarding. Exploratory laparoscopy revealed congestion in the distal jejunum and proximal ileum with no evidence of ischemia. He underwent an appendectomy, which was reported as showing mild acute inflammation. Postoperatively, the patient continued to experience abdominal pain. He was also noted to develop palpable purpuric rash on the lower extremities (Fig. 1). His initial investigations showed normal blood counts and renal functions, urine protein was 33 g/L, urine protein:creatinine ratio was 1252 mg/mmol and urine microscopy showed granular casts. Both complement levels (C3, C4) were low and serum serological markers were negative, including anti-nuclear antibodies (ANA), anti-double stranded DNA, extracable nuclear antigen, antineutrophil cytoplasmic antibodies and anti-C1q antibody. Skin biopsy was compatible with leukocytoclastic vasculitis. The clinical impression was HenochSchonlein purpura (HSP). The child’s renal condition deteriorated with the development of generalized edema, oliguria and worsening renal functions. Renal biopsy showed a diffuse endocapillary proliferative glomerulonephritis with many neutrophils in all glomeruli. A few glomeruli had wireloop type lesions and hyaline thrombi. There was full house staining on immunoflorescence for immunoglobulin A (IgA), IgG, IgM, C3, C1q and fibrin, all of which were of equal and strong intensity, and hence the biopsy was reported as compatible with diffuse lupus nephritis class IV-G (A) (Fig. 2). He was pulsed with methylprednisone 1 g for 3 days followed by oral prednisolone 1 mg/kg/day and was started on mycophenolate mofetil (600 mg/m) twice daily along with lisinopril. There was a dramatic clinical response with normalization of renal parameters within 3 months. His serological markers continue to be negative on 1-year follow-up and no evidence of any other clinical or serological markers for systemic lupus erythematosus (SLE). SLE is a complex disease that is characterized by an autoantibody response to nuclear and cytoplasmic antigens. The presence of ANA is recognized as one of the

Rickettsial Infection Diagnosed in a Clinical Context in Oman

Dear Sir, An 11-year-old boy presented to the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, in 2016 with a one-week history of scattered nodular-like erythematous lesions over the arms, petechial rashes over the dorsa of both feet and itchy maculopapular urticarial rashes over both thighs [Figure 1]. He had a high-grade fever which reached 39.5 °C as well as a headache, generalised body pain and swelling around the joints. The patient lived in Muscat and had no known history of tick bites, travel or contact with animals. A systemic examination revealed hepatomegaly and splenomegaly (both organs enlarged to 3 cm below the costal margin) as well as generalised body tenderness, myalgia and meningism. The bilateral knee and ankle joints were swollen with some restriction in movement, mainly flexion with partial extension. All vital signs were stable and normal, except for the persistent high-grade fever, which responded only partially to antipyretic medications. Initial investigations showed mild proteinuria (700 mg/dL over a 24-hour period) and microscopic haematuria (1+). A complete blood count revealed normal amounts of haemoglobin cells and platelets; however, the patient had leukocytosis (white blood cell count: 24,000/m3) and neutrophilia (absolute neutrophil count: 21,400/m3). His coagulation profile was normal. Further investigations indicated high C-reactive protein levels (125 mg/L), a high erythrocyte sedimentation rate (58 mm/hour), persistent unexplained low sodium levels (128 mmol/L), low chloride levels (89 mmol/L), very high creatine kinase levels (781 U/L), low serum albumin levels (29 g/L), normal renal function, normal complement levels, elevated alanine aminotransferase levels (190 IU/L) and elevated aspartate aminotransferase levels (250 U/L). An initial chest X-ray, ultrasound of the abdomen and gallium scan were normal. Autoimmune causes, including vasculitis, immune deficiency, malignancy and pyrexia of unknown origin, were ruled out with various investigations, including antinuclear antibody, anti-double-stranded DNA, antineutrophil cytoplasmic autoantibody, antimyeloperoxidase antibody and antiproteinase 3 antibody tests, skin and bone marrow aspirate biopsies, cultures and lumbar punctures. However, the patient had persistently high inflammatory markers. Serology screening for Brucella, Leishmania, Mycoplasma, malaria and Leptospira infections was negative. A bronchoalveolar lavage for tuberculosis resulted in a negative acid-fast bacilli smear with normal cytology and negative cultures. Virology screening was negative for cytomegalovirus, Epstein-Barr virus and acute hepatitis infections. Virology screening of nasopharyngeal aspirate was negative for influenza A and B viruses and subtype A H1N1 as well as enteroviruses, Coxsackieviruses, human immunodeficiency virus and Coxiella burnetii bacteria. The patient was treated with several combinations of antibiotics, including ceftriaxone and piperacillin/ tazobactam, vancomycin and meropenem, vancomycin and erythromycin as well as ciprofloxacin and gentamicin. However, he did not respond to these treatments. At this point, his fever had persisted for 35 days. A funduscopic letter to the editor Sultan Qaboos University Med J, November 2016, Vol. 16, Iss. 4, pp. e529–530, Epub. 30 Nov 16 Submitted 4 Jul 16 Revision Req. 4 Aug 16; Revision Recd. 18 Aug 16 Accepted 25 Aug 16 doi: 10.18295/squmj.2016.16.04.025

Nocardia asteroides peritoneal dialysis-related peritonitis: First case in pediatrics, treated with protracted linezolid

Nocardia asteroides is a rare pathogen in peritoneal dialysis-related peritonitis. We report on a 13-year-old female with Nocardia asteroides peritonitis complicated by an intra-abdominal abscess. Linezolid was administered intravenously for 3 months and followed by oral therapy for an additional 5 months with close monitoring for adverse effects. The patient was discharged after 3 months of hospitalization on hemodialysis. The diagnosis and management of such cases can be problematic due to the slow growth and difficulty of identifying Nocardia species. The optimal duration of treatment for Nocardia peritonitis is not known. Linezolid can be used for prolonged periods in cases of trimethoprim/sulfamethoxazole-resistant cases with close monitoring for adverse effects.