Profile of Patients With Von Gierke Disease From India.

Molecular diagnosis of Von Gierke disease is possible by mutation analysis of G6PC gene. GSD type 1a cases account for 20 % of glycogenoses in our center. We diagnosed ten unrelated patients with glycogen storage disease based on clinical, biochemical and histopathology investigations. Mutation analysis was done by sequencing the G6PC gene. Two unrelated patients were found to be homozygous for a novel mutation c.355 C>G (p.H119D). They were born to non-consanguineous parents from Karnataka. This suggests founder effect. Mutation detection confirms the diagnosis and assists in counseling and prenatal diagnosis.

Opsismodysplasia.

Opsismodysplasia is a rare osteochondrodysplasia with micromelia and platyspondyly. The authors report on a neonate with opsismodysplasia. During the antenatal period, polyhydramnios was noted. This is the first report of opsismodysplasia from India. Significant observation was antenatal polyhydramnios.

Fabry disease: A treatable lysosomal storage disorder.

Fabry disease is a lysosomal storage disease with an X-linked inheritance pattern, which presents in childhood as acroparaesthesias. Its non-specific symptoms often lead to delays in the diagnosis. We report the case of a 13-year-old boy who presented with typical acroparaesthesia of Fabry disease, his younger brother had gastrointestinal manifestations of the disease and their mother’s symptoms suggested that she is a carrier. Enzyme replacement therapy helped in ameliorating the patient’s symptoms and preventing complications such as renal failure, stroke and cardiovascular disorders.

Issues in counseling for Down syndrome.

We studied the background information, concerns and specific queries of thirty-four families of children with Down syndrome. Majority of the parents were aware that their child has Down syndrome and has or will have mental retardation. However, most of the families were ignorant about the lack of curative treatment, chromosomal nature of the disorder and prenatal screening and testing options.

A new autosomal recessive disorder of bilateral frontotemporal pachygyria without microcephaly: report of a case and review of literature.

Pachygyria is a disorder of neuronal migration. We report an Indian family with four siblings with developmental delay, infrequent seizures, normal head size and mild to moderate mental retardation. Two of them had bilaterally symmetrical frontotemporal pachygyria. Dysmorphism and neurological signs were absent in the affected subjects. Affected male and female siblings with normal parents suggests autosomal recessive mode of inheritance. We believe these cases represent a new autosomal recessive disorder of neuronal migration. Other similar cases of lissencephaly are reviewed.

S252W mutation in Indian patients of Apert syndrome.

Two common mutations in the exon IIIa of fibroblast growth factor receptor 2 account for majority of the cases of Apert syndrome. They can be analyzed by amplifying the segment followed by testing for the abolition of restriction sites. We evaluated two children with typical features of Apert syndrome. A segment of FGFR2 exon IIIa was amplified by polymerase chain reaction. Restriction fragment length polymorphism was analyzed using enzymes MboI and BglI respectively for S252W and P253R mutations. The DNA segment was sequenced using ABI 310 automated DNA fragment analyzer. Both the patients showed S252W mutations. DNA sequencing confirmed the results of the restriction fragment length polymorphism. Our study is the first report from Indian subcontinent to show the prevalence of S252W mutation among Apert syndrome patients from Indian origin.

Immunological response to two hepatitis B vaccines administered in two different schedules.

OBJECTIVES: To evaluate the antibody response to a plasma derived hepatitis B vaccine containing pre-S and S antigens and a recombinant vaccine containing only S antigen and compare the two vaccines in 0, 1, 2 and 0, 1, 6, schedules METHODS: One hundred fifty nine healthy infants were randomized to receive the vaccines in two different schedules. Anti HBs titers were estimated prior to the vaccination and then one-month following the second and third doses. RESULTS: Both the vaccines produced a high rate of seroconversion and seroprotection. The antibody response was similar with both the vaccines and the 0, 1, 6, schedule induced a significantly higher antibody level than the 0, 1, 2, schedule. CONCLUSION: 0, 1, 6 schedule produces a higher antibody level than 0, 1, 2 schedule though both the schedules have good seroconversion and seroprotection rates with both the vaccines.

Anotia and facial palsy: unusual features of cardiofacial syndrome.

The authors report a child with features of Cardiofacial syndrome with anotia and facial paralysis. This is the first report of such an association.

TNFR2 gene polymorphism in coronary artery disease.

BACKGROUND: Recently atherosclerosis and coronary artery disease (CAD) are considered to be inflammatory diseases. The genetic polymorphism in inflammatory markers has been well studied and found to be associated with development of CAD. AIM: To study the association of biallelic polymorphism at position 196 in exon 6 of tumor necrosis factor 2 (TNFR2) gene and coronary artery disease. SETTINGS AND DESIGN: The study design was a prospective case control study conducted at a tertiary referral center mainly catering to the north Indian population. MATERIALS AND METHODS: One hundred and fifty angiographically proven patients with coronary artery disease and one hundred and fifty age matched controls were genotyped for TNFR2 gene by polymerase chain reaction followed by analysis of restriction fragment length polymorphism. STATISTICAL ANALYSIS: Genotype frequencies were compared in patients and controls by Chi-square test. Binary logistic regression analysis was used to examine the relationship between genotypes and disease, incorporating other variables into the model. RESULTS: The incidence of CAD in those with MM genotype was 65% and in those with RM genotype was 42%. Genotype frequency shows significant association of MM genotype with development of CAD (P < 0.001; odds ratio-2.585; 95% confidence interval 1.533-4.359). The association of TNFR2 genotype with CAD persisted on logistic regression analysis. CONCLUSION: MM genotype of TNFR2 gene is associated with development of CAD and RM genotype appears to be protective.

T1 and M1 polymorphism in glutathione S-transferase gene and coronary artery disease in North Indian population.

BACKGROUND: DNA damage has been found to play an important role in atherosclerosis and coronary artery disease. Genetic polymorphisms of the genes coding for enzymes involved in the metabolism of genotoxins result in different phenotypes with respect to their ability to detoxify these agents. In the present study the contribution of the polymorphism in the glutathione S-transferase gene to the development of coronary artery disease has been investigated. METHODS: One hundred and ninety seven angiographically proven patients with coronary artery disease and one hundred and ninety eight age-matched controls were genotyped for glutathione S- transferase polymorphism by polymerase chain reaction. Genotype frequencies were compared in patients and controls by Chi-square test. Binary logistic regression was used to examine the relationship between genotype and disease, incorporating other variables into the model. RESULTS: GSTT1 null genotype was significantly decreased in patients with coronary artery disease. No significant association was found with GSTM1 genotypes. No such association was seen with smokers. CONCLUSION: Null genotype of GSTT1 is protective against coronary artery disease in our population.

Congenital and inherited ophthalmologic abnormalities.

OBJECTIVE: To identify genetic disorders associated with ophthalmologic abnormalities; type and frequency of various ophthalmologic abnormalities associated with selected genetic and inherited disorders; and devise a suitable classification for ophthalmologic abnormalities. METHODS: Pediatric cases referred with mental retardation, congenital malformations and suspected genetic and metabolic disorders were enrolled prospectively. Relevant clinical details (including an ophthalmologic examination) and investigations were recorded. RESULT: Of the 1308 patients enrolled, 679 (51.9%) had ophthalmologic abnormalities. 458 cases (67.45%) out of these 679 had mental retardation and 20 (2.94%) had neuroregression. Environmental (12.22%) and chromosomal anomalies (10.9%) were the largest etiological groups. Down syndrome was the commonest of the chromosomal anomalies and mongoloid slant and epicanthic folds were its commonest ophthalmologic features. Mucopolysaccharidoses (21.4%), Wilson disease (19.64%), oculocutaneous albinism (16.07%) and lipid storage disorders (14.29%) were the most common inborn errors of metabolism associated with ophthalmologic abnormalities. Of the 39 cases with Mendelian inheritance of disorders, autosomal dominant disorders (56.41%) were the commonest associated with ocular abnormalities. A simple anatomical classification has been devised for various ophthalmologic abnormalities encountered (wherein, positional and adnexal abnormalities were the commonest). CONCLUSION: Up to 50% of cases referred to the genetic services have ophthalmologic abnormalities. Conditions including chromosomal abnormalities, metabolic disorders, Mendelian syndromes and environmental factors are associated with ocular abnormalities. Anatomically, positional and adnexal abnormalities are the commonest.