Treatment-induced copper deficiency in two patients with Wilsons disease

Copper is an essential trace element that is vital to the health of all living cells. However, like all essential elements, its serum level must be kept within normal values; otherwise, conditions of toxicity or deficiency can result, each of which has its own unique set of adverse health effects. Wilson's disease [WD] is an inherited disease of copper accumulation that can cause liver and neurological affection. Its management depends on removal of excess copper using copper chelators such as D-penicillamine or trientine, which increase the urinary excretion of copper. In a more recent approach, zinc has been used to decrease copper accumulation. We present two WD cases that developed copper deficiency as a result of their treatment. These cases improve our understanding and management of copper deficiency in WD and highlight the importance of copper-level monitoring in WD

Maternal MTHFR C677T genotype and septal defects in offspring with Down syndrome: a pilot study

While abnormal folate/homocysteine metabolism has been implicated as an etiology for the development of both CHD and DS, recent studies and meta-analyses did not consider MTHFR C677T genotype as a maternal risk factor for either of these conditions alone. To investigate if methylenetetrahydrofolate reductase [MTHFR] C677T genotype is a maternal risk factor for the development of congenital heart disease [CHD] only in children with Down syndrome [DS]. Molecular analysis of MTHFR C677T and serum folic acid was done for sixty-one consecutive mothers of children with CHD in the form of septal defects [26 with DS and 35 without DS] and another 61 mothers of apparently healthy children [without DS or CHD]. The frequency of CT genotype was significantly higher in mothers of children with AV canal [whether in DS or non-DS] when compared to ASD and in mothers of DS with AV canal when compared to controls. The frequency of TT genotype was higher in mothers of DS with ASD than controls but statistically insignificant. In non-DS mothers, the distribution of the genotypes did not differ in relation to the type of CHD. The mean folic acid level did not differ between different study groups. MTHFR 677CT genotype could be implicated as a maternal risk factor for septal defects especially in children with DS. Carriers of this genotype may have more risk of development of AV canal in their children. A major limitations of this study was the small sample size and so further studies on a larger sample of patients and their mothers in addition to measurement of homocysteine level in this population is needed to investigate this theory and to clarify the actual role of MTHFR polymorphism and the risk of development of CHD in DS

Consanguinity and its relevance to clinical genetics

Consanguineous marriages have been practiced since the early existence of modern humans. Until now, consanguinity is widely practiced in several global communities with variable rates. The present study was undertaken to analyze the effect of consanguinity on different types of genetic diseases and child morbidity and mortality. Patients were grouped according to the types of genetic errors into four groups: Group I: Chromosomal and microdeletion syndromes. Group II: Single gene disorders. Group III: Multifactorial disorders. Group IV: Diseases of different etiologies. Consanguineous marriage was highly significant in 54.4% of the studied group compared to 35.3% in the control group [P < 0.05]. Consanguineous marriages were represented in 31.4%, 7.1%, 0.8%, 6%, 9.1% among first cousins, one and a half cousins, double first cousins, second cousins and remote relatives respectively in the studied group. Comparison between genetic diseases with different modes of inheritance showed that recessive and multifactorial disorders had the highest values of consanguinity [78.8%, 69.8%, respectively], while chromosomal disorders had the lowest one [29.1%]. Consanguineous marriage was recorded in 51.5% of our cases with autosomal dominant diseases and in 31% of cases with X linked diseases, all cases of mental retardation [100%] and in 92.6% of patients with limb anomalies [P < 0.001]. Stillbirths, child deaths and recurrent abortions were significantly increased among consanguineous parents [80.6%, 80%, 67%] respectively than among non consanguineous parents. In conclusion, consanguineous marriage is significantly higher in many genetic diseases which suggests that couples may have deleterious lethal genes, inherited from common ancestor and when transmitted to their offsprings, they can lead to prenatal, neonatal, child morbidity or mortality. So public health education and genetic counseling are highly recommended in our community

Hypothyroidism could be the only manifestation of mitochondrial T8993C mutation in Leigh syndrome

Mitochondrial DNA-associated Leigh syndrome is a part of a continuum of progressive neurodegenerative disorders caused by abnormalities of mitochondrial energy generation. Mitochondrial T8993C and T8993G mutations account for 10-20% of these cases. T8993C is generally associated with milder phenotype than T8993G mutation. Here we report an Egyptian family with T8993C mutation with unusual early onset of severe phenotype in three sisters [consisting of regression of previously acquired motor and mental milestones after an attack of viral infection] and hypothyroidism as the only presenting symptom in their brother. The mother [like her son] carried the T8993C mutation and was asymptomatic. This unusual lack of manifestation could be attributed to different percentages of mutated mitochondrial DNA in the brain or muscle or perhaps to some unknown protective factor. The hypothyroidism could be a simple association, but to the best of our knowledge, no previous reports have described hypothyroidism in carriers of this mutation

Oral-facial-digital syndrome type II: transitional type between mohr and varadi

We report a 2 months old boy, the first in order of birth of non-consanguineous parents, with several typical features of oral-facial-digital syndrome type II [OFDS II] including cleft lip, high arched palate, retromicrognathia, preaxial polysyndactyly of hands and feet, duplication of thumb and hallux. Interestingly, the patient also had mesoaxial polydactyly of the left hand with extra metacarpal bones characteristic of OFDS. VI, however mentality and MRI brain were normal. This unusual association may suggest an additional subgroup of OFDSs or a variant of OFDS II due to variable gene expression or a transitional type between OFDS II and OFDS VI

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 subtle chromosomal rearrangements in an Egyptian sample of children with unexplained mental retardation

Mental retardation is present in about 1-3% of individuals in the general population, but it can be explained in about half of the cases. A descriptive study was carried out to screen for subtle chromosomal rearrangements in a group of Egyptian children with idiopathic mental retardation [IMR] to estimate its frequency if detected. The study enrolled 30 patients with IMR, with the perquisite criteria of being <18 years at referral, their IQ <70, and manifesting at least one of the criteria for selection of patients with subtelomeric abnormalities. Males were 63.3% and females were 36.7%, with a mean age of 7.08 +/- 4.22 years. Full history taking, thorough clinical examination, IQ, visual, and audiological assessment, brain CT scan, plasma aminogram, pelvi-abdominal ultrasonography, echocardiography, and cytogenetic evaluation using routine conventional karyotyping, high resolution banding [HRB], and fluorescent in situ hybridization [FISH] technique with appropriate probes were carried out for all studied patients. All enrolled patients had apparently normal karyotypes within 450 bands resolution, except for one patient who had 46, XY, [del [18] [p11.2]]. HRB and FISH showed subtle chromosomal rearrangement in 10% of cases that have been proven to be subtelomeric in 2 cases, i.e., 6.8%: 46, XY, dup [17] [p13.3], 46, XY, del [2] [q36.1-36.3], and non-subtelomeric in one case, 5.5%, 46, XX, ins [7;?] [q22;?]. To conclude, in children with IMR and clinical phenotype indicative of a suspected chromosomal anomaly, once recognizable syndromes have been excluded, abnormalities that include the ends of chromosomes must be searched for using HRB and subtelomeric FISH even when conventional karyotyping fails to demonstrate any abnormality

Connexin 26 [GJB2] mutation in KID syndrome: an Egyptian patient

Keratitis +/- ichthyosis +/- deafness [KID] syndrome is a rare disorder characterized by the occurrence of localized erythematous scaly skin lesions, severe bilateral keratitis, and sensorineural deafness. Other ocular manifestations include corneal epithelial defects and scarring, which cause progressive decline of visual acuity and may eventually lead to blindness. To our knowledge, few cases have been reported worldwide and none were reported from the Middle East Arab countries. Here we report the first Egyptian patient with this syndrome

Colchicine resistant FMF is not always true resistance

Crohn's disease and familial Mediterranean fever are both inflammatory diseases characterized by similar clinical manifestations. The concurrence of the two diseases may pose a challenge to diagnosis and treatment. In this report, we present a child with familial Mediterranean fever and undiagnosed Crohn's disease which made him apparently resistant to colchicine therapy. Symptoms of Crohn's disease were masked by the resistant fever of FMF. Amelioration of symptoms of both diseases was achieved when treatment of both diseases were gradually introduced. Searching of IBD in children with colchicines resistant FMF is mandatory, as both diseases have similar symptoms and responsible genes may modify one another

Consanguineous matings among Egyptian population

Consanguinity is the blood relationship that exists among individuals that descend from a common ancestor. The objectives of the study was to explore the frequency and socio-economic determinants of consanguinity in Egypt. The study was carried out using a cross-sectional approach which included 10,000 unselected couples. All couples were recruited from the prenatal, gynecologic, neonatal and pediatric clinics as well as vaccination centers in three hospitals one in Lower Egypt [Cairo] and two in Upper Egypt [Sohag and Assuit]. Consanguineous marriage is still high in Egypt [35.3%], especially among first cousins [86%]. However the frequency varies by region. It is higher in Sohag [42.2%] and Cairo [36.1%] than in Assuit [21.7%]. Also it was higher in rural areas [59.9%] than in semi-urban and urban areas [23.5% and 17.7%, respectively]. It was associated with decreased age of marriage, low educational level and unemployment in the couples which means that the socio-economic determinants are still working in maintaining this high rate of consanguinity. This is in addition to the high divorce rate and increased number of unmarried females in Egypt. Advances in genetics have led to a deeper understanding of the effect of inbreeding on the occurrence of genetic diseases. As prolonged parental inbreeding has led to a background of homozygosity above that predicted by simple models of consanguinity, we encourage counselors to call on a reliable computer program for calculation of the recurrence risks in these families

Neonatal screening of lysosomal storage diseases [LSD]: hope for the future

It is well known that the best public health effort in genetics is the government programs that carry out population screening of all newborns to identify infants with genetic disorders for which early treatment can prevent or at least ameliorate that consequence. The concept of screening newborns for inherited metabolic disorders was the brainchild of Robert Guthrie, an upstate New York microbiologist with a passion to prevent the devastating and irreversible neurological damage sustained by victims of untreated phenylketonuria [PKU]. The solution he developed was a simple and inexpensive bacterial inhibition assay for phenylalanine in blood. Lysosomal storage disorders [LSDs] represent a group of more than 45 distinct genetic diseases, each one resulting from a deficiency of a particular lysosomal protein or, in a few cases, from nonlysosomal proteins that are involved in lysosomal biogenesis. 1- Availability of treatment for LSD and advantages of early detection 2-Frequency of LSDs in population 3- Availability of screening tests

Genetic evaluation of non-selected group of patients with cranio facial dysmorphism

A number of congenital and acquired conditions can affect the skull, face and jaws in a wide range of craniofacial abnormalities that commonly present at birth or in early in infancy. The aim of the present study was to evaluate clinically as well as cytogenetically a non-selected group of Egyptian children with craniofacial dysmorphism whether isolated or part of the syndrome. The study included 30 patients from 28 families. Consanguinity was present in 42.8% of families and a similar affected family member was present in 6 patients [20%]. Cytogenetic analysis using high resolution karyotype was done to 24 patients. Patients were classified according to the aetiology of dysmorphism into five groups. Group 1 included patients with chromosomal abnormalities [two patients [6.7%]] and one patient with microdeletion syndrome [Rubenstein Taybi syndrome [3.3%]] which needs FISH and molecular testing for confirmation. Craniofacial dysmorphism due to monogenic disorders was present in 34.3%, multifactorial aetiology in 20%, environmental factors in 6.7%, and unknown aetiology in 20% of cases. In conclusion, the aetiology of craniofacial dysmorphism is very heterogeneous. Good observation and systematic examination can narrow the differential diagnosis and the laboratory investigations needed. High resolution karyotype is essential in all of these cases

Acrocallosal syndrome [ACS]

Acrocallosal syndrome [ACS] is a rare autosomal recessive genetic disorder with hypoplasia / agenesis of corpus callosum, moderate to severe mental retardation, characteristic craniofacial abnormalities, distinctive digital malformations and growth retardation. In this paper we present a three month old girl with typical features of this syndrome.

MURCS association: a case report

MURCS association is a rare developmental disorder that affects females. The acronym MURCS stands for Mullerian, Renal, Cervicothoracic Somite abnormalities. It appears to occur randomly [sporadic] with a frequency of 1 in 50.000 females. In this paper, we present a two-year-old girl with typical features of this syndrome in association with right deviation of anorectal canal, subglottic stenosis and unilateral oblique inguinal hernia