Haemaphagocytic lymphohistiocytosis presenting as neonatal liver failure: a case series

Background and study aim: Haemophagocytic lymphohistiocytosis [HLH] is a life-threatening clinical syndrome with liver involvement varying from mild dysfunction to severe fulminant failure. The aim of this study was to present a case series of four HLH patients presenting with acuw liver failure [ALF] in the neonatal period

Patients and methods: All four patients were neonates at the onset of symptoms. They presented to Cairo University Pediatric Hospital with ALF; they underwent prompt investigations including determination of ferritin, fibrinogen, and higlyceride levels as part of our ALF workup. Further investigations were tailored according to the associated clinical features and the results of preliminary investigations

Results: HLH was diagnosed according to HLH-2004 criteria. Three patients fulfilled at least five out of eight criteria. Fever, splenomegaly, elevated ferktin levels, and low fibrinogen levels were present in all patients. The fourth patient had a serum ferritin level >10,000 nglml, favouring the diagnosis of HLH, despite fullilling only four out of eight criteria. For three patients, positive consanguinity and previous sibling death were reported, suggesting a genetic aetiology of HLH

Conclusion: ALF can be the presenting feature of HLH; thus, a high index of suspicion is necessary. Fever is a hallmark, especially in neonates. Diagnosis is important for this potentially treatable condition

Glycogen storage disease type III in Egyptian children: a single centre clinico-laboratory study

Glycogen storage disease type III [GSD III] is an autosomal recessive disorder caused by deficiency of glycogen debrancher enzyme and is characterised by clinical variability. We herein describe the clinical and laboratory findings in 31 Egyptian patients with GSD III presenting to the Paediatric Hepatology Unit, Cairo University, Egypt. Eighteen patients [58%] were males. Their ages ranged between 6 months to 12 years. The main presenting complaint was progressive abdominal distention in 55%. Twelve patients [38.7%] had a history of recurrent attacks of convulsions; four had an erroneous diagnosis of hypocalcaemia and epilepsy. Dolllike facies was noted in 90%. Abdominal examination of all cases revealed abdominal distention and soft hepatomegaly which had bright echogenicity by ultrasound. Hypertriglyceridaemia was present in 93.6%, hyperlactacidaemia in 51.6% and hyperuricaemia in 19.4%. Liver biopsy showed markedly distended hepatocytes with well distinct cytoplasmic boundaries and 32% had macrovesicular fatty changes. Serum creatine kinase was elevated in 64.6% of patients and correlated positively and significantly with age [r = 0.7 and P = <0.001], while serum triglycerides correlated negatively with age [r = -0.4 and P = 0.05]. Blood glucose assessment and search for hepatomegaly in an infant with recurrent seizures may prevent delay in the diagnosis. A huge soft liver reaching the left midclavicular line that appears echogenic on ultrasonography is characteristic of GSD III. A distended hepatocyte with rarified cytoplasm is pathognomonic but not diagnostic. Hypertriglyceridaemia correlates negatively with age, in contrary to CK level

clinical study of Wilson's disease: the experience of a single Egyptian paediatric hepatology unit

Most paediatric patients with Wilson's disease [WD] present with hepatic manifestations, but some may have neurologic or psychiatric features. Our aim was to define the clinical, biochemical features and the outcome of therapy of a group of Egyptian children diagnosed with WD. The study was carried out at the Paediatric Hepatology Unit at Cairo University Children's Hospital, Egypt; 54 patients were diagnosed with WD from 1996 to 2009. The diagnosis was based on low serum ceruloplasmin levels, increased urinary copper concentrations before or after D-penicillamine challenge and/or the presence of Kayser-Fleischer [K-F] rings. The clinical presentation was as follows: hepatic presentation in 33 patients [61%], hepato-neurologic 3 [5.5%], neurologic 5 [9.3%] and presymptomatic 13 [24%]. Twelve couples had more than one affected sib. Increased urinary copper concentrations before or after D-penicillamine challenge was found in all patients, low serum ceruloplasmin in 97% and K-F rings in 31.5%. All patients were treated with penicillamine and zinc sulphate except one presymptomatic case who was treated with zinc sulphate only. Three patients underwent liver transplantation and eight patients died after a median duration of treatment of 6 months [1-36]. The hepatic symptoms improved with treatment but the neurological symptoms remained stationary. Clinical and biochemical assays remain the standard for diagnosis of WD. Penicillamine and zinc therapy can effectively treat WD with hepatic symptoms. Liver transplantation remains life saving for those with fulminant and end stage WD. Screening for presymptomatic sibs is of utmost importance

Paraoxonase gene polymorphism and serum paraoxonase activity: relationship with type I diabetes and nephropathy

Human serum paraoxonase-I [PON1] is physically associated with high density lippprotein [HDL] and has been implicated in the prevention of LDL lipid peroxidation. PON1 gene displays several polymorphisms that influence both its level of expression and its catalytic activity. The goal of this study was to examine the association between paraoxonase-1 [PON1] activity and gene polymorphism and the micro-vascular complications in children and adolescence suffering from type 1 DM [TIDM]. Case-control study. One study centre at a University hospital. Thirty eight patients, with type 1 diabetes [n=38], 13 patients presenting with diabetic nephropathy [mean age 18.76 +/- 5.59 years. 8 males and 5 females] and 25 without diabetic nephropathy [mean age 14.48 +/- 3.69 years. 14 males and 11 females] and 16 healthy controls [mean age 12.38 +/- 8.25 years, 10 males and 6 females]. The allele variants of PON1 gene polymorphisms in the PON1 coding region Q192R and L55M have been identified by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Serum PON1 enzyme activity was measured spectrophotometrically. Serum PON1 activity was significantly decreased in complicated diabetics when compared to both non-complicated patients and the control persons [103.33 +/- 35.46 nmol/ml/min, 462.57 +/- 200.69 nmol/ml/min and 1132 +/- 317.61 nmol/ml/min respectively]. As regards PON1 Q192R polymorphism, the R allele was more frequent in complicated diabetics versus both non-complicated diabetics and controls [p=0.0113 and p=0.001 respectively]. PON1 192QR genotype is a risk factor for developing type 1 diabetes OR=7.8; 95% CI [1.12-65.7] with p=0.043. PON1 192QR genotype and 192R allele are risk factors for developing micro-vascular complications with OR =6.40 and 4.00; 95% CI [1.44.28.29] and [1.15-13.87] with p=0.01 and 0.023 respectively. In PON1 L55M polymorphism, non significant differences in the genotype or allele frequency were found between T TIDM, both complicated and non-complicated diabetics and control persons. The association of PON1 Q192R polymorphisms, lower PON1 activity and poorer diabetic control found in patients with diabetic nephropathy further support an idea of genetic factors contributing to development of vascular complications in diabetes

Serum osteocalcin and urinary deoxypyridinoline: response prediction in children on recombinant human growth hormone replacement therapy

In children and adolescents, markers of bone and collagen metabolism reflect the dynamics of skeletal growth and development. Treatment with recombinant human growth hormone [rhGH] has a marked effect on bone formation and resorption. This bone remodeling is well reflected on specific markers that can be measured in blood and urine. The aim of this study was to assess the potential role of bone remodeling markers in the assessment of the response to rhGH in GHD children. The study included 35 children and adolescents, 20 of which had GHD [14 boys and 6 girls], with a mean age of 14.46 +/- 2.47 years and 15 controls [8 boys and 7 girls], 11.3 +/- 2.01 years old, Anthropometric measurements were performed, and blood and morning urine samples were collected for estimation of total serum calcium, inorganic phosphorus, total ALP, OC and urinary DPD. DPD values were corrected to urinary creatinine concentrations and expressed as deoxypyridinoline/creatinine [DPD/cr] ratio. Patients started rhGH therapy, laboratory assays were repeated after 3 months, and anthropometric measurements were repeated at 3-monthly intervals for one full year. Bone turnover markers [calcium, phosphate, ALP, OC, and urinary DPD] were measured before and after 3 months of onset of rhGH. The results showed that in all patients, rhGH evoked continuous improvements in height standard deviation scores [SDS], with no significant effect on weight SDS. Height velocity SDS [HVSDS] was high during the first 3 months of rhGH, decreased thereafter, supporting the waning of rhGH, Pre-treatment Level of the ALP and OC were lower in patients than controls. Differences in serum OC levels between patients and controls were high enough to discriminate between the two groups [p<0.0001]. Both increased substantially after rhGH, Basal and after 3 months value of ALP, OC and DPDlcr ratio was 106.95 +/- 32.76 and 144.75 +/- 38.20 IUIL; 6.80 +/- /- 3.74 and 31.78 +/- 26.12 nglml; 23.69 +/- 22.49 and 37.75 +/- 29.28; with p=0.008, p=0.0001 and p>0.05, respectively. There was a significant positive correlation between the both serum ALP basal and after 3 months and overall 1st year HVSDS [r=0.69, p=0.019, p=0.86, p=0.001, respectively]. There was a significant positive correlation between serum levels of OC and urinary DPDlcr ratio in both, patients before rhGH [r=0.538, p=0.014] and controls [r=0.654, p=0.008]. Basal values of DPD/cr were positively correlated with HVSDS after 3 months [r=0.48, p0.034] and after 3 months of rhGH DPD/cr were positively correlated with height SDS [r=0.46, p=0.04]

Conclusion: bone formation markers, namely ALP and OC and bone resorption markers, namely DPD increase during growth hormone [GH] therapy. At least, one full year of observation is mandatory to detect the impact of rhGH on height measurements, while bone-remodeling markers may be used as early predictors of the long-term response to the expensive rhGH in a child with GHD. OC measurement may be used as an adjuvant assay, together with height measurements and GH stimulation tests, in the initial diagnosis of GHD as it could differentiate between patients and controls

Evaluation of growth hormone in polytransfused thalassemic patients with short stature and effect of L - carnitine treatment

Objective: Evaluation of growth hormone in poly- transfused thalassemic patients with short stature and effect of L-carnitine therapy in patients with growth hormone deficiency

Method: The study included. 30 beta-thalassemic patients with mean age 13.8 +/-1.7 yr and 30 children with constitutional short stature as a control. Anthropometric measurements, thyroid profile, insulin like growth factor -1 [IGF-1] and growth hormone [GH] provocation by 2 tests were done at the beginning of the study. Anthropometric measurements and pubertal assessment were done for all patients after 6 months. Eight patients with inadequate GH response to both clonidine and ITT were given L-Carnitine treatment at a dose of 50 mg/kg/day divided into three doses for 6 months. They were reevaluated after 6 months of therapy

Results: Twelve [40%] patients had sub-clinical hypothyroidism [diagnosed by normal free thyroxin level and elevated thyroid stimulating hormone], 10 [33.3%] patients had growth hormone deficiency. Peak GH and growth velocity /{cm and Standard Deviation Score [SDS]] were significantly lower while weight [SDS] and weight / height SDS were significantly higher than patients with constitutional short stature [P < 0.05]. A significant positive correlation was found between height and target height [cm]. Eight patients with growth hormone deficiency were given L-carnitine for 6 months [50 mg/Kg/day]. After L-carnitine treatment hemoglobin level, peak GH, IGF-1 and growth velocity [cm and SDS] were significantly increase and the number of blood transfusions was significantly decrease [p<0.05]. Delta changes were higher in height [cm and SDS], estimated mature height, sitting height and lower in target height - height [SDS and cm] six months after L-carnitine treatment in beta-thalassemic patients with growth hormone deficiency [p <0.05]

Conclusion: Growth hormone[GH] deficiency is an etiologic factor in beta-thalassemia patients with short stature. L-Carnitine can promote GH secretion and growth