Seema Kapoor

Infantile Onset Spinocerebellar Ataxia 2 (SCA2) A Clinical Report With Review of Previous Cases

Autosomal dominant cerebellar ataxia type I is a heterogenous group of spinocerebellar ataxias with variable neurologic presentations, with age of onset varying from infancy to adulthood. Autosomal dominant cerebellar ataxia type I is composed mainly of 3 prevalent spinocerebellar ataxia types with different pathogenic loci, specifically spinocerebellar ataxia 1 (6p24-p23), spinocerebellar ataxia 2 (12q24.1), and spinocerebellar ataxia 3 (14q32.1). The shared pathogenic mutational event is the expansion of the CAG repeat that results in polyglutamine extended stretches in the encoded proteins. CAG repeat disorders generally show the phenomenon of anticipation, which is more often associated with paternal transmission. In this report, we describe a patient with infantile-onset spinocerebellar ataxia type 2 (∼320 CAG repeat) who inherited the disease from his father (47 CAG repeats). We have summarized the clinical, neuroimaging, electroencephalographic (EEG), and molecular data of previous cases and attempt to highlight the most consistent findings. Our intent is to help treating clinicians to suspect this disorder and to offer timely genetic counseling for a currently potentially untreatable disorder.

Evaluation of C677T polymorphism of the methylenetetra hydrofolate reductase gene and its association with levels of serum homocysteine, folate, and vitamin B12 as maternal risk factors for Down syndrome

AIMS AND OBJECTIVE: Evaluation of C677T polymorphisms of the methylenetetra hydrofolate reductase (MTHFR) gene and its association with level of serum homocysteine, folate, and vitamin B12 as possible maternal risk factors for Down syndrome. DESIGN: This was a case–control study. MATERIAL AND METHODS Fifty-two mothers (mean age 27.6 years) with babies having free trisomy 21 of North Indian ethnicity and 52 control nonlactating mothers (mean age 24.9 years) of same ethnicity attending services of genetic lab for bloodletting for other causes were enrolled after informed written consent. Fasting blood was collected and was used for determination of plasma homocysteine, vitamin B12, and folate (serum and RBC), and for PCR amplification of the MTHFR gene. RESULTS: The prevalence of MTHFR C677T polymorphism in north Indian mothers of babies with trisomy 21 Down syndrome was 15.38% compared to 5.88 % in controls. The difference between two groups was not statistically significant (P = 0.124). Low serum folate was demonstrated in 34.62% of cases vs. 11.54% in controls, which was significant (P = 0.005). Low RBC folate was found in 30.7% of cases versus 11.53% in controls, which was not significant (P = 0.059), when analyzed independently. But on multiple regression analysis the difference was statistically significant. Low serum vitamin B12 was found in 42.31% of cases versus 34.62% in controls, which was not significant (P = 0.118). The mean serum homocysteine in cases was 10.35 ± 0.68 while controls were 9.02 ± 0.535. CONCLUSION: Serum levels of folate were low in cases. The RBC folate levels were comparable in both groups. However the combined serum folate and RBC folate were low in cases compared to control groups. Homocysteine levels in our study were higher in Down syndrome mothers compared to controls; however high-serum level of Homocysteine had no association with MTHFR polymorphism. No association of serum vitamin B12 with MTHFR polymorphism in occurrence of Down syndrome births was found. Peri- or preconceptional folate supplementation may therefore lead to a decline in DS births, if supported by larger studies.

Detecting protein losing enteropathy by Tc-99m dextran scintigraphy: a novel experience.

Objective: To evaluate protien using enteropathy by Tc-99m dextran scintigraphy.Methods: Methods for detecting protein loss from the intestine revolve around fecal nitrogen excretion, the clearance of α-1 antitrypsin in stools and by endoscopic biopsy.Result: The diagnosis of protein-losing enteropathy (PLE) can also be established by a scintigraphic method that is noninvasive, simple and requires no patient preparation or motivation. This diagnostic modality can also delineate the site of protein loss, thereby offering a targeted approach, and if need be, surgery. Radiolabelling of a non-protein, noncolloidal, nonparticulate and biofriendly molecule like dextran with Technetium-99m for imaging enteric protein loss was utilized in imaging eight children with PLE.Conclusion: The results were encouraging. The authors advocate the use of this diagnostic tool in identifying patients with PLE, particularly in the pediatric age group.

An Indian boy with griscelli syndrome type 2: case report and review of literature.

Griscelli syndrome 2 is a rare autosomal recessive disorder of pigmentary dilution of hair, skin, splenohepatomegaly, pancytopenia, immune and neurologic dysfunction. Clinical course is characterized by recurrent infection triggered by uncontrolled T-lymphocyte and macrophage activation, called hemophagocytic syndrome. Since the primary presentation is with depigmented hair, we attempt to highlight diagnostic difficulties in such cases in developing countries like ours where pigmentary changes in hair and skin are commonly attributed to severe malnutrition. We also evaluated phenotype of all 10 cases of genotype (c.C550T; p.R184X), collected from published literature worldwide and emphasize the potential role of above mutation as hotspot in Southeast Asian region.

Cerebellar Atrophy in a Child with Valproate Toxicity

In the treatment of epilepsy, selecting an appropriate antiepileptic drug for each individual patient requires matching the patient’s clinical needs with the agent’s specific pharmacological attributes. In many situations, the final choice of an antiepileptic drug may need a change due to the agent’s side-effect profile. The authors report a ten-year-old child with Lennox Gastaut syndrome who developed recurrence of seizures, hyperammonemic encephalopathy and cerebellar atrophy on valproate therapy. Valproate was discontinued and lamotrigine was added followed by good control of seizures. Cerebellar atrophy as a serious adverse side effect of valproate therapy, has been infrequently reported.

Heparin co-factor II Thrombin complex as a biomarker for mucopolysaccharidosis: Indian experience

BackgroundSerum heparin cofactor II-thrombin complex (HCII-T) is an emerging biomarker for mucopolysaccharidosis disease (MPS I and MPS II).MethodsSeventeen cases (6 MPS I and 11 MPS II) and sixty healthy controls were enrolled in study, conducted from September 2008 to December 2012. The mean ± SD age of MPS1 (n=6, 5 males) and MPS II was 7.02 ± 3.25 and 5.2 ± 2.15 years, respectively. Disease status was confirmed by clinical features and enzyme assay. Urinary glycosaminoglycans were measured in spot urine samples and expressed in relation to creatinine content. HCIIT measurement was done using sandwich ELISA at enrolment and after 12 and 24 months of recruitment.ResultsUrinary glycosaminoglycans and HCIIT were elevated in all patients compared to their healthy controls. Both markers could not discriminate between the type of mucopolysaccharidosis.ConclusionHeparin Cofactor II Thrombin Complex is a good biomarker for mucopolysaccharidosis I and II.

Pendred Syndrome in a Newborn with Neck Swelling: A Case Report

BACKGROUND Pendred syndrome is a rare autosomal recessive condition, characterized by functional impairment of thyroid gland and sensorineural hearing loss. The syndrome presents in patients with homozygous or compound heterozygous mutation. The presentation in the form of neck mass in a newborn is rare. CASE CHARACTERISTICS A 1 month old baby presented to us with neck mass, which was found to be an enlarged thyroid gland. Thyroid function tests were consistent with hypothyroidism. Further evaluation revealed moderate sensorineural hearing loss; genetic analysis showed that baby was homozygous for the known mutations causing the disease. INTERVENTION Thyroid hormone replacement and hearing habilitation were done. Follow up showed regression of the neck mass and normalization of thyroid function tests. Genetic counseling of the family was done. MESSAGE Identification of the exact cause of congenital hypothyroidism can prevent grave consequences later on for the patient as well as for the family.

A novel CANT1 mutation in three Indian patients with Desbuquois dysplasia Kim type.

Desbuquois dysplasia (DBQD) is a rare skeletal dysplasia characterized by severe short stature, laxity, dislocation of multiple joints and developmental delay. DBQD is clinically heterogeneous. Distinct radiographic hand abnormalities such as the presence of extra-ossification distal to the second metacarpal or normal hand has led to its classification into types 1 and 2. Furthermore, the third type of DBQD, Kim type has been reported which is characterized by short metacarpals and elongated phalanges. However, DBQD Kim type has been exclusively reported in Japanese and Korean and its clinical characteristics remain to be delineated. Mutations in the calcium-activated nucleotidase 1 (CANT1) gene have been reported in all three types of DBQD. Previously reported patients with DBQD Kim type had a common mutation c.676G>A (p.Val226Met), which had a common founder between Japanese and Korean. Here, we report 3 Indian patients with DBQD, Kim type from 2 families which were unrelated to each other. We identified a novel mutation of CANT1, c.467C>T (p.Ser156Phe), in all the patients in the homozygous form. Our results show that DBQD Kim type is not exclusive to East Asians and also report a novel mutation from the Indian subcontinent.

Prenatal screening: Perspective for the pediatrician

Pediatricians are the first contact of a child with genetic disorders such as Down Syndrome. After diagnosis, parents often express and wish that if it was possible to detect it during pregnancy and could it be avoided in the future pregnancy. This makes it essential that pediatricians should have some idea about the basic screening methods and strategy used during pregnancy.

Rectal Involvement in Neutropenic Enterocolitis

Neutropenic enterocolitis is a common gastrointestinal complication in children undergoing chemotherapy for a variety of malignancies. It usually involves ileum and caecum, and involvement of rectum has rarely been reported. The authors report neutropenic enterocolitis in a child undergoing chemotherapy for acute lymphoblastic lymphoma which presented with ileus along with a mass like lesion in the rectum.