Kamal Akl

Skin lesions, angioedema, eosinophilia, and hypocomplementemia.

A six-year-old girl with recurrent urticaria and angioedema, vasculitis, and probable renal disease exhibited marked blood eosinophilia, increased levels of serum IgE, circulating Clq precipitins, and hypocomplementemia with evidence of activation of complement by the classic pathway. Biopsies of skin and muscle revealed heavy infiltrations of the vessel walls with eosinophils. Immunofluorescence studies revealed deposition of IgM, IgE, and C3 in the vessel walls. Exacerbations of the disease were associated with an increase in the eosinophil count and a decrease in the serum levels of C4 and C3. Remission was achieved with corticosteroid therapy. This patient has many features in common with the syndrome of skin lesions, angioedema, and hypocomplementemia recently described in adults.

Epidemiological characteristics of Candida species colonizing oral and rectal sites of Jordanian infants

BackgroundThere is evidence that Candida colonization contributes to increasing invasion of candidiasis in hospitalized neonates. Few studies investigated the epidemiology and risk factors of Candida colonization among hospitalized and non-hospitalized infants. This prospective study investigated the major epidemiological characteristics of Candida species colonizing oral and rectal sites of Jordanian infants.MethodsInfants aged one year or less who were examined at the pediatrics outpatient clinic or hospitalized at the Jordan University Hospital, Amman, Jordan, were included in this study. Culture swabs were collected from oral and rectal sites and inoculated on Sabouraud dextrose agar. All Candida isolates were confirmed by the Remel RapID yeast plus system, and further investigated for specific virulence factors and antifungal susceptibility MIC using E-test. Genotyping of C. albicans isolates was determined using random amplified polymorphic DNA (RAPD) analysis method.ResultsA total of 61/492 (12.4%) infants were colonized with Candida species by either their oral/rectal sites or both. Rectal colonization was significantly more detected than oral colonization (64.6% verses 35.4%), particularly among hospitalized infants aged more than one month. The pattern and rates of colonization were as follows: C. albicans was the commonest species isolated from both sites and accounted for 67.1% of all isolates, followed by C.kefyr (11.4%), each C. tropicalis and C. glabrata (8.9%) and C. parapsilosis (3.8%).A various rates of Candida isolates proved to secrete putative virulence factors in vitro; asparatyl proteinase, phospholipase and hemolysin. C. albicans were associated significantly (P < 0.05) with these enzymes than other Candida species. All Candida isolates were susceptible to amphotericin B and caspofungin, whereas 97% of Candida species isolates were susceptible to fluconazole using E-test.The genetic similarity of 53 C. albicans isolates as demonstrated by dendrogram revealed the presence of 29 genotypes, and of these one genotype accounted for 22% of the isolates.ConclusionThis study presents important epidemiological features of Candida colonization of Jordanian infants.

Sanjad Sakati syndrome: a case series from Jordan.

Sanjad Sakati syndrome is a rare autosomal recessive disorder that has been described in Arabs. We report 8 patients from 7 Jordanian families, 6 of whom underwent genetic testing and were found to have a 12 bp (155-166 del) deletion within the tubulin-specific chaperone E (TBCE gene) in exon 3 at 1q42-43. All patients had severe growth retardation, distinct phenotypic features and hypoparathyroidism. Parental consanguinity was recorded in all families. This is the first genetically proven case series of Sanjad Sakati syndrome in Jordan.

The clinical spectrum of idiopathic hyperuricosuria in children: Isolated and associated with hypercalciuria/hyperoxaluria

The clinical manifestations of hyperuricosuria (HU) are usually underestimated by the clinician. The aim of this study was to review the clinical spectrum of symptomatology of HU and to evaluate the presence of associated hypercalciuria (HC) and hyperoxaluria (HX). A retrospective review was done on 64 children with HU seen between January 2004 and December 2008. The patients were divided into HU 19, HU + HC 4, HU + HX 21 and HU + HC + HX 20. The mean age at diagnosis was 80 months (range six to 156 months). Duration of follow-up ranged was from six to 66 months. There were 228 symptomatic episodes for 64 patients (males 31, females 33). The relationship of symptomatology to age and gender were not significant. The most common symptoms were abdominal pain 67.2% (in 7/44 it was localized to the right lower quadrant, mimicking appendicitis), flank pain 59.4%, increased urinary frequency 43.4%, urgency 39%, enuresis 31.25%, oliguria 29.7%, dysuria 25%, red urine 20.35%, vaginal itching 15.21%, dribbling 14.06%, orange urine 12.5%, hesitancy 12.5% and penile pain 7.81%. To our knowledge, the vaginal itching and penile pain were not previously described. Family history was positive for stones and/or gout in 62.5%. The presence of a positive family history and red urine were significant (P-value <0.05) for the presence of an underlying HU. In the presence of recurrent abdominal/flank pain, hematuria without proteinuria or edema and urological symptomatology, especially in the presence of red urine, and a positive family history of gout or stones, a search for HU is in order. This will avoid unnecessary and invasive investigations.

Original articleMolecular analysis of the CTNS gene in Jordanian families with nephropathic cystinosisAnálisis molecular del gen CTNS en familias jordanas afectadas por cistinosis nefropática

OBJECTIVE Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder that is characterised by the accumulation of the amino acid cystine in several body tissues due to a mutation in the CTNS gene, which encodes the cystinosin protein. The aim of this study was to sequence the coding exons of the CTNS gene in five different Jordanian families and one family from Sudan with nephropathic cystinosis. METHODS Probands initially presented with Fanconi syndrome symptoms. An eye examination showed the accumulation of cystine crystals in the cornea by the age of 2 years, suggesting cystinosis. All of the coding exons and flanking intronic sequences and the promoter region of the CTNS gene were amplified using polymerase chain reaction and subjected to sequencing. RESULTS None of the probands in this study carried the European 57-kb deletion in the CTNS gene. Seven variants in the coding and promoter sequence of the CTNS gene were identified in the probands of this study. Two of these variants were a CTNS mutation that was previously identified in a heterozygous genotype in two different patients of European descendant. The two mutations were c.829dupA in exon 10 and c.890G>A in exon 11. The proband of family 2 was compound-heterozygous for the two mutations. CONCLUSION This study is the first molecular study of infantile nephropathic cystinosis in Jordan. We successfully identified the causative CTNS mutations in Jordanian families. The results provide a basis for the early detection of the disease using molecular tools in a highly consanguineous Jordanian population.

Molecular analysis of the CTNS gene in Jordanian families with nephropathic cystinosis

OBJECTIVE Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder that is characterised by the accumulation of the amino acid cystine in several body tissues due to a mutation in the CTNS gene, which encodes the cystinosin protein. The aim of this study was to sequence the coding exons of the CTNS gene in five different Jordanian families and one family from Sudan with nephropathic cystinosis. METHODS Probands initially presented with Fanconi syndrome symptoms. An eye examination showed the accumulation of cystine crystals in the cornea by the age of 2 years, suggesting cystinosis. All of the coding exons and flanking intronic sequences and the promoter region of the CTNS gene were amplified using polymerase chain reaction and subjected to sequencing. RESULTS None of the probands in this study carried the European 57-kb deletion in the CTNS gene. Seven variants in the coding and promoter sequence of the CTNS gene were identified in the probands of this study. Two of these variants were a CTNS mutation that was previously identified in a heterozygous genotype in two different patients of European descendant. The two mutations were c.829dupA in exon 10 and c.890G>A in exon 11. The proband of family 2 was compound-heterozygous for the two mutations. CONCLUSION This study is the first molecular study of infantile nephropathic cystinosis in Jordan. We successfully identified the causative CTNS mutations in Jordanian families. The results provide a basis for the early detection of the disease using molecular tools in a highly consanguineous Jordanian population.

Isolated myositis as a sole presentation of familial Mediterranean fever.

A seven-year-old previously healthy Jordanian boy was admitted to the Jordan University Hospital with the chief complaint of inability to walk of one day duration. The patient had associated myalgia not involving the bones or joints. No history of exercise, fever, vomiting, diarrhea, headache, abdominal, chest, or joint pains. Family history: parents were first cousins, and there was negative history for FMF, although the paternal grandfather had renal failure of undetermined etiology. Physical examination: The heart rate was 99 beats/minute, temperature 36.7 C, respiratory rate 22/min, and the weight and height were 25 kg and 112 cm, respectively. Except for a bilateral tenderness of the thigh and calf muscles, the remainder of the physical examination was unremarkable. Laboratory investigations

Recurrent ecchymoses after acute tacrolimus intoxication

Sirs, We report on a 3.5-year-old girl with acute tacrolimus overdose associated with bleeding tendency. The patient who had steroid-resistant nephrotic syndrome secondary to immunoglobulin M (IgM) nephropathy was put on tacrolimus. Other medications included acetylsalicylic acid, prednisone, and amlodipine. Initial tacrolimus trough level was 8.1 ng/ml (target 7–12 ng/ml). One week later, the patient started complaining of abdominal pain, poor appetite, vomiting, diarrhea, headache, tachypnea, and leg pains in addition to gingival bleeding, easy bruisability, and epistaxis. Positive findings on physical examination were blood pressure 150/ 110 mmHg (>99th percentile) and multiple ecchymotic spots all over the body. Pertinent laboratory data were hemoglobin 10 gm/dl and platelets 307,000/mm. Prothrombin time (PT) was 13.6/13 s, partial thromboplastin time (PTT) 98/30 s, and bleeding time 12.5 (2.5–10). Uric acid was 12 mg/dl, potassium 3.1 mEq/L, and magnesium 1.89 mg/dl. Liver function tests, clotting factors, and serum creatinine were normal. Tacrolimus trough level was 28 ng/ml (target 7– 12 ng/ml). Tacrolimus was discontinued and fresh frozen plasma was given repeatedly. Four months after the initial episode, our patient still gets recurrent ecchymosis. Tests for platelet aggregation disclosed IaIIa deficiency in the mother (asymptomatic) and child. No significant toxicity has been reported in most cases of acute tacrolimus overdose [1, 2]. Ecchymosis has not been reported previously in acute tacrolimus overdose in nontransplant patients. In one study in Italian kidney transplant patients whose immunosuppressive regimen included tacrolimus, ecchymosis was present in 3% of cases [3]. Inherited glycoprotein IaIIa deficiency and interaction with acetylsalicylic acid may have contributed in our case, especially to the prolonged duration of the ecchymosis.

Neurological and cardiac complications in a cohort of children with end-stage renal disease.

Adult patients with chronic kidney disease are at risk of major neurologic and cardiac complications. The purpose of this study is to review the neurological and cardiac complications in children with end-stage renal disease (ESRD). A retrospective review of medical records of children with ESRD at Jordan University Hospital was performed. All neurological and cardiac events were recorded and analyzed. Data of a total of 68 children with ESRD presenting between 2002 and 2013 were reviewed. Neurological complications occurred in 32.4%; seizures were the most common event. Uncontrolled hypertension was the leading cause of neurological events. Cardiac complications occurred in 39.7%, the most common being pericardial effusion. Mortality from neurological complications was 45%. Neurological and cardiac complications occurred in around a third of children with ESRD with a high mortality rate. More effective control of hypertension, anemia, and intensive and gentle dialysis are needed.

RE: A guideline for the inpatient care of children with pyelonephritis.

To the Editor: We read with great interest the article by Chishti et al,1 and would like to congratulate the authors for developing these timely guidelines. However, the authors mentioned that febrile urinary tract infection associated renal scarring is highest in the first year of life. For infants less than one year of age, it would be more appropriate to use the term renal parenchymal defect instead of scarring, as recommended by the NICE guidelines.2 Parenchymal defects discovered in infancy are usually the result of renal dysplasia rather than acquired scars. Renal dysplasia occurs when the developing kidney is subjected to an in utero insult, including vesicoureteral reflux, at a critical period of nephrogenesis.3 Along the same lines, in the dysplastic kidney, recurrent febrile urinary tract infections add insult to injury, thus speeding up kidney function deterioration.4