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

Outcome of enzyme replacement therapy in children with Gaucher disease: the Egyptian experience

Gaucher disease is the most prevalent lysosomal storage diseases which results from inherited deficiency in the glucocerebrosidase enzyme. Three main clinical forms have been described: type I non-neuropathic, type II acute neuropathic and type III subacute neuropathic. Although it is panethnic disease, its presentation has some ethnic specific characteristics. In this work, we present specific characteristics as well as our experience in diagnosing and managing a group of Egyptian patients with this disease. The study included 48 patients with Gaucher disease attending Children's Hospital, Ain Shams University. The recombinant enzyme imiglucerase [cerezyme] was given in a dose of 60 U/kg/2 weeks. Haemoglobin, platelet count, plasma chitotriosidase, and abdominal ultrasound were assessed before starting therapy and every 6 months. Molecular analysis was done to 23 patients. At presentation, the mean age was 3.54 +/- 3.8 years. Ten patients [20.8%] had type I, 6 had type II [12.5%] and 26 had type III Gaucher disease [66.7%]. The commonest genotype was homozygous L444P which was present in 13 patients [56.5%] followed by homozygous N370S; found in three patients [13.04%]. Follow up after enzyme replacement therapy revealed a significant increase in weight and height, haemoglobin level and platelet count and slow reduction in the liver span and spleen length. Bone manifestations showed slow but complete improvement while neurological and respiratory manifestations were partially ameliorated with individual variations. To conclude, since most of Egyptian children with GD have type III disease and L444P/L444P genotype, a minimum dose of 60 U/kg/2 weeks should be maintained until adulthood. Higher doses started at an early age may delay the progression of neurological symptoms. Pulmonary involvement is not rare in Egyptian patients and may respond to dose increase or dose fractionation. Cardiovascular and renal involvement should be further studied in our population

Screening for phenylketonuria and galactosemia among Egyptian newborns in Menoufiya governorate

Was to study the prevalence of phenylketonuria and galactosemia in Menoufiya Governorate newborns. Among 3000 newborns, their mean ages were 9.3 +/- 2.43 days; mean weight was 3.1 +/- 0.82 Kg. Among them 1800[60%] males and 1200 [40%] females who attended the central hospital and medical units for BCG vaccination in the duration from March 2005 to May 2008. The results showed that the mean of phenylalanine level was 3.19 +/- 1.82 mg/dl and the mean total galactose level was 3.34 +/- 2.23mg/ dl, among the 3000 neonates, 2183 [72.8.%] had phenylalanine levels ranging from 2-5 mg /dl, 705 [23.5%] had levels ranging from 5-7 mg/dl, 111[3.7%] had levels ranging from 7-10 mg/dl and one newborn [0.033%] had phenylalanine level of 22 mg/dl. The results for galactosemia screening assay showed that 2528 neonates [84.3%] had galactose levels ranging from 2-6 mg/dl, 450 [15%] had levels ranging from 6-8 mg/dl, 21[0.7%] had levels ranging from 8-12 mg/dl and one newborn [0.033%] had galactose level of 19 mg/dl. The child was reassayed and was found to be true hypergalactosemia l20mg/dl. We concluded that the prevalence of each of phenylketonuria and galactosemia in Menoufiya Governorate in the 3000 newborn tested was 1/3000 [0.03%]. So, we estimate that about 333 neonates are affected every year with PKU and 333 with galactosemia as one million babies are born yearly, which could be prevented. The prevention of such treatable disorders depends on planning an efficient screening programme especially within three weeks after birth. So we recommend multicenter studies to encourage national neonatal screening programmes specialy for these treatable diseases

Inborn errors of metabolism revealed by organic acid profile analysis in high risk Egyptian patients: six years experience

To determine the prevalence and types of inborn errors of amino acid or organic acid metabolism in a group of high risk Egyptian children with clinical signs and symptoms suggestive of inherited metabolic diseases. 117 [79 males = 67.5% and 38 females = 32.5%] high risk patients with signs and symptoms of a metabolic disorder were studied, their ages ranged from 3 days to 12 years. Analysis of urine organic acids by gas chromatography/mass spectrometry [GC/MS] was performed to all patients. 22[18.8% of the total] cases were diagnosed with different types of aminoacidopathies or organic acidurias. The disease profile showed increased lactate in 12 cases [54%], glutaric aciduria type I 3 cases [13%], phenylketonuria 2 cases [9%], maple syrup urine disease 1 case [4.5%], glutaric aciduria type II 1 case [4.5%], methylmalonic aciduria 1 case [4.5%], Canavan disease 1 case [4.5%] and non ketotic hyperglycemia 1 case [4.5%]. The results demonstrate the importance of the organic acid profile in the diagnosis of high risk patients. The diagnosed organic acid pattern in this study showed that 10.2% of the patients had a mitochondrial energy defect

Hepatomegaly: a major clinical sign in some metabolic disorders

This study included 18 cases with hepatomegaly referred to the Human Genetics Department, National Research Centre with a suspicion of a metabolic disorder from 2006 to 2008. The aim of our study was to find out the importance of hepatomegaly as sign for many metabolic disorders and their frequency among other disorders with hepatomegaly. All cases were subjected to clinical and biochemical studies. 12 cases, 66%, [10 males 83.4% and 2 females 16.6%] were diagnosed with a metabolic disease. 8 cases with mucopolysaccharidosis [MPS] [3 cases MPS I, 3 cases MPS II, one case MPS III and one case MPS VI]; one case with glycogen storage disease [GSD]; one case with galactosemia and 2 cases with Niemann-Pick disease type C. 75% of the diagnosed cases showed positive consanguinity and the remaining 25% were three patients with MPS II with an X linked mode of inheritance

Genetic heterogeneity in spondylo-epi-metaphyseal dysplasias: a clinical and radiological study

Spondylo-epi-metaphyseal dysplasias [SEMD] are a heterogeneous group of skeletal disorders characterized by defective growth and modeling of the spine and long bones. Different types are described in the literature. Accurate classification of SEMDs is essential for proper genetic counseling. This study included 20 cases of SEMDs diagnosed by clinical and radiological findings. Cases were classified based on additional associated clinical and/or radiological features into 7 subtypes. Different subtypes were discussed with review of the literature. The study illustrated the heterogeneity of SEMDs and emphasized the importance of detailed and meticulous clinical genetic and biochemical evaluation in addition to comprehensive radiological investigations for such group of disorders. It also recommends further molecular studies to identify the molecular bases of the different types

Clinical spectrum associated with some structural cerebellar abnormalities

To review the clinical, neuroimaging, cytogenetic, and biochemical studies obtained in 20 patients with different cerebellar structural abnormalities presenting at variable ages of onset with variable signs and symptoms. These patients visited the Clinical Genetics Department, National Research Center, Cairo, Egypt during the period from September 2002 to September 2003. All patients were subjected to complete personal and family history taking 3 generation family pedigree construction and full clinical examination, including complete eye evaluation. Metabolic screening, chromosomal examination and brain CT or MRI, or both, were also carried out. Patients with cerebellar structural abnormalities were broadly divided into those with cerebellar hypoplasia [15 patients; 75%], cerebellar atrophy [3 patients; 15%] and cerebellar white matter abnormalities [2 patients; 10%]. Further, cerebellar hypoplasia was subdivided into cerebello-vermal hypoplasia [4 patients; 20%], vermal-cerebellar hypoplasia [3 patients; 15%] and associated with involvement of other features such as brain stem [4 patients; 20%], posterior fossa [1 patient; 5%]; and intracranial calcification [3 patients; 15%]. This study showed that the type of cerebellar structural abnormality is not the main determining factor of the clinical outcome, but rather the underlying etiology. A high incidence of mostly autosomal-recessive inheritance was diagnosed in 65% of the patients with cerebellar structural abnormalities. Nevertheless, the high rate of consanguinity [18 cases; 90%] with mean inbreeding coefficient of 0.05312 and the similarly affected sibs highlights the role of the autosomal recessive gene in our country

Plasma chitotriosidase activity in patients with. beta-thalassemia

Variable increase in plasma chitotriosidase levels have been reported in Italian patients with beta thalassemia major and intermedia. We measured plasma chitotriosidase levels in Egyptian patients with beta thalassemia to ascertain its use as a universal marker of the disease and /or response to therapy. Chitotriosidase levels in 30 children [1.5-15 years] with beta thalassemia major and 10 children [6-15 years] with beta thalassemia intermedia were compared with other measures of the disease, such as ferritin, hemoglobin F, pre-transfusion hemoglobin, and liver function tests. Plasma chitotriosidase levels were normal in all cases with thalassemia intermedia [median 22.5, range 8.8-69 nmol/ml/h]. Eight patients with thalassemia major had elevated levels [<69.4 nmol/ml/h]. A significant correlation was found between plasma chitotriosidase and hemoglobin F, ferritin levels, and with duration of transfusion. Normal chitotriosidase levels in thalassemia intermedia and elevated levels only with thalassemia major and correlation with duration of blood transfusion may reflects status of iron overload in macrophages. The highly significant correlation with hemoglobin F might reflect the role of thalassemia genotype in chitotriosidase production. Thus there may be a role for monitoring chitotriosidase in patients with beta thalassemia. Our results confirm results of the Italian cohort; however in the latter chitotriosidase levels were much higher

New methodology in newborn screening for cystic fibrosis in Egypt

We used a three-tier neonatal screening method for cystic fibrosis disease. A total of 924 newborns, 458 males and 466 females, were screened by taking a heel prick on Guthrie cards during the first, three days after labour. The studied newborns were divided into two groups: Group I included forty high risk neonates and Group II included 884 randomized full term neonates. For all 942 newborns immunoreactive trypsinogen [IRT] was determined in neonatal blood spot. Forty positive cases [IRT equal to or higher than 60 ng/mL] were confirmed by sweat electrolyte testing. It was positive [equal to or higher than 50 mEq/L] in only three cases. DNA analysis using ARMS-PCR amplification technique for detection of F508 mutation was done to the three positive infants. One did not show the F508 mutation on both allels. The other two carried the F508 mutation on one allele. All three cases were recalled to exclude CF disease