With a very large population and high birth rate, and consanguineous marriage favoured in many communities, there is a high prevalence of genetic disorders in India. An estimated 495,000 infants with congenital malformations, 390,000 with G6PD deficiency, 21,400 with Down syndrome, 9,000 with β-thalassaemia, 5,200 with sickle cell disease, and 9,760 with amino acid disorders are born each year. The prevalence of late-onset multi-factorial disorders (including coronary artery disease, hypertension and psychiatric disorders) is also large. Due to inadequate diagnostic, management and rehabilitation facilities, the burden of these disorders is greater than in Western countries. Although genetic diseases receive little attention from the health services, research funding by the government has been liberal. Community control of common disorders like thalassaemia, Down syndrome, neural tube defects, and muscular dystrophies deserves high priority, and genetic services should be integrated into the existing primary health care and medical services. Most genetic counselling would have to be provided through training physicians who staff the district and medical school hospitals. To ensure future progress, there is a need to establish additional departments of medical genetics in medical schools.

Significant hypothyroidism, transient or permanent, but persisting beyond 2 months of age is common in VLBW babies. There is a delayed rise in TSH in some, and secondary screening at 1 month of age detects babies deemed by local paediatric endocrinologists as needing treatment.

Glutaric aciduria type I (GA I), a cerebral organic acidaemia with the potential for severe neurological consequences, can now be detected by tandem mass spectrometry newborn screening. Early detection with implementation of careful management strategies appears to lessen the likelihood of neurological damage. We assessed the outcome in all 10 GA I patients detected in New South Wales during the last decade. Three patients were detected clinically and 7 by newborn screening. Diagnosis was confirmed by detection of significantly elevated urinary 3-hydroxybutyrate and glutarate in urine, isolated elevation of glutarylcarnitine in plasma, typical clinical and MRI findings in several, and mutation analysis or enzyme analysis on cultured skin fibroblasts in 4 cases. The birth frequency was 1:90,000. Following diagnosis, treatment was initiated in all children with oral carnitine (100 mg/kg per day) and a low-protein diet supplemented with a lysine-free, low-tryptophan amino acid formula. Disability was assessed in fields of motor, cognitive and speech development and scored according to Kyllerman. Clinically diagnosed patients were all symptomatic, with severity scores (out of 9) of 3, 5 and 9. Six of seven patients detected by newborn screening are asymptomatic, 4 being aged 2-6 years. One patient had a severe decompensation at 7 months, despite full management advice and treatment, and later died. Our data support previous findings that early diagnosis reduces neurological complications, but show that even with early diagnosis and careful management severe complications may ensue in some.

Objective To offer accurate prenatal diagnosis of lysosomal storage disorders in early pregnancy.Method Prenatal enzymatic diagnoses of Gaucher, Fabry, Pompe, Niemann Pick A/B, Tay Sach, Sandoff, GM1, mucoplysaccharidoses, Wolman, Krabbe, Metachromatic leukodystrophy and Batten diseases were made in uncultured chorionic villi samples by fluorometric/spectrophotometric methods.Results Of 331 prenatal enzymatic diagnosis, 207 fetuses (67%) were normal and 124 (37%) were affected. The interpretation of affected, normal and carrier fetuses was done using their respective reference ranges as well as % enzyme activity of normal mean. The prenatal molecular confirmation was feasible in 43 biochemically diagnosed fetuses. Of the 207 normal reported fetuses, post natal enzymatic confirmation was done in 23 babies, clinical status of another 165 babies was assessed as unaffected via questionnaire on telephone and 19 were lost to follow-up. In affected pregnancies, 123 opted for termination of which 44 were confirmed enzymatically after abortion. A single false positive was determined to be a carrier by prenatal mutation analysis and carried to term. ConclusionWe recommend uncultured chorionic villi for reliable prenatal enzymatic diagnosis of various lysosomal storage disorders on account of the low rate of false positive (0.5%) and false negative (2.2%) results.

Advanced molecular, cytogenetic and biochemical techniques have been a useful addition for genetic counseling and prenatal diagnosis in India.

Fanconi-Bickel Syndrome (FBS) is a rare autosomal recessive disorder of carbohydrate metabolism. The defect in the GLUT 2 receptors in the hepatocytes, pancreas and renal tubules leads to symptoms secondary to glycogen storage, glucose metabolism and renal tubular dysfunction. Derangement in glucose metabolism is classical with fasting hypoglycemia and post-prandial hyperglycemia. The authors report a 4-year-old boy who presented with failure to thrive, motor delay, protuberant abdomen and was noted to have huge hepatomegaly with glycogen deposition in liver, and renal tubular acidosis. Gene sequencing revealed homozygous mutation, c.1330T > C in SLC2A2 gene, thus confirming the diagnosis of FBS. Only three mutations have been reported from India so far. The primary reason for referral to authors’ hospital was for liver transplantation, but an accurate diagnosis led to avoidance of the major surgery and streamlining of treatment with clinical benefit to the child and family.

The protocol for identification of mutations in cases of CF in developing countries would have to include a different set of mutations than those reported from western countries.

The objective of the present study was to analyze the utility of noninvasive prenatal testing (NIPT) for aneuploidies in a developing country like India. NIPT was offered to 500 pregnant women, after review of data of the ongoing pregnancy. Pre-test counseling included the different methodologies of testing, their benefits, limitations, turnaround time and interpretation of the result and was offered to all. Different vendors were used for the test. The results were explained in a post-test counseling session. The indications of NIPT were positive second (36.6 %) or first (22 %) trimester screen, advanced maternal age with or without positive biochemical screen (24.6 %), ultrasound soft markers (10.8 %), previous history of Down syndrome (4.6 %) and anxious couple (0.1 %). No aneuploidy was detected in 484 samples. In 1 case, no result was available. Fifteen (3 %) cases showed positive results. These included 8 cases of trisomy 21, 3 cases of trisomy 18, 3 cases of monosomy X, and 1 case of triploidy. Confirmatory testing revealed 6 cases (40 %) to be false positive-1 case of trisomy 21, 1 case of trisomy 18, 3 cases of monosomy X, and 1 case of triploidy. Of 484 cases, 230 have delivered healthy neonates, while the rest have yet to deliver. Four cases had to discontinue pregnancy due to complications in later pregnancy but unrelated to the NIPT results. Noninvasive prenatal test qualifies as an 'advanced' screening test, and requires invasive diagnostic tests for confirmation of the positive results. The pre-and post-test counseling is essential to appropriately explain the limitations, benefits, and the results to the couple. Recommendations are made for the appropriate deployment of this new technology in developing countries.