David J. Lloyd

A high frequency of the MTHFR 677C>T polymorphism in Scottish women with epilepsy: possible role in pathogenesis.

The inheritance of most forms of epilepsy is usually considered to be multifactorial, although a number of single gene causes are known. Most previous studies of epilepsy genetics have implicated ion channel genes or ligand receptors. In a previous study of children with adverse effects of prenatal exposure to antiepileptic drugs, we noted an increased frequency of the methylene tetrahydrofolate reductase (MTHFR) 677C>T polymorphism in the mothers. To investigate this further, a new cohort of women with epilepsy has been identified from maternity hospital records and genotyped for polymorphisms in MTHFR, serine hydroxymethyl transferase (SHMT1), methionine synthase (MTR) and methionine synthase reductase (MTRR). Healthy blood donors were genotyped as controls. The frequency of the MTHFR 677TT genotype was significantly higher in women with idiopathic generalised epilepsy than in healthy controls (p=0.012, OR 2.26, 95%CI 1.13-4.51). No association was detected for the other polymorphisms tested. The MTHFR 677C>T polymorphism may be a susceptibility factor for epilepsy, and its higher frequency in women with epilepsy may contribute to the increased risk of malformation in children of women with epilepsy.

Problems of detecting mosaicism in skin. A case of trisomy 8 mosaicism illustrating the advantages of in situ tissue culture

A case of mosaic trisomy 8 is described and the accuracy of flask culture and in situ culture techniques in detecting chromosomal mosaicism in tissues discussed. The advantages of the in situ method are illustrated and the importance of mixed colonies in defining mosaicism highlighted. The implications for prenatal diagnosis of mosaicism are pointed out.

Fetal anticonvulsant syndromes and polymorphisms in MTHFR, MTR, and MTRR†

The malformations found in fetal anticonvulsant syndromes (FACS) are associated with folic acid deficiency and methylene‐tetrahydrofolate reductase (MTHFR) polymorphisms in the general population. To investigate a possible association between FACS and MTHFR genotype, we recruited 200 mothers who had taken anti‐epileptic drugs in pregnancy, and delivered at Aberdeen Maternity Hospital over a 26‐year period. Clinical findings in the mothers and their 337 children were documented. A clinical algorithm was devised to diagnose FACS objectively. Case‐parent triads were genotyped for polymorphisms in MTHFR, serine hydroxymethyl transferase (SHMT1), methionine synthase (MTR), and methionine synthase reductase (MTRR), and analyzed by log‐linear regression. No effect of the childs genotype on congenital malformation, neurodevelopmental disorder or FACS was detected using this method. The risk of having a child with congenital malformation or FACS was three to four times higher for mothers who were MTHFR 677TT homozygotes compared with MTHFR 677CC homozygotes. MTR 2756A > G and MTRR 66A > G genotype frequencies in children with FACS and neurodevelopmental disorder were different from those in healthy blood donor controls.

Surgical Treatment of Necrotizing Enterocolitis: A Population-Based Study in the Grampian Region, Scotland

Ninety-two cases of necrotizing enterocolitis (NEC) were diagnosed in the Grampian Region of Scotland between 1978 and 1984, for a regional incidence of 2.2/1,000 live births. Twenty-seven cases (29.3%) required surgery, 19 acutely and eight for delayed stricture. Acute operative mortality was 10.5%. Disease-related mortality was 3.3%, and overall mortality was 8.7%. Follow-up ranged from 15 to 77 months for surgical patients, with only three of 23 survivors having increased bowel frequency.

GROUP B STREPTOCOCCAL INFECTION IN THE NEWBORN Criteria for Early Detection and Treatment

Abstract. Recent reports indicate that the group B haemolytic streptococcus has now assumed a major role in neonatal septicaemia in the United Kingdom. Of particular concern are the absence of premonitory signs, the fulminating nature of the infection and the high mortality. 31 cases from which this organism was isolated during the first week of life included 5 cases of neonatal septicaemia, 4 of which proved fatal. An attempt was made (a) to identify the group of neonates at greatest risk and (b) to formulate guidelines for early detection and treatment. Study indicates the importance of apnoea as a sign of infection particularly in those infants who are preterm, of low birth weight and asphyxiated. There is need for aggressive bacteriological screening and early administration of antibiotics to prevent the high mortality from group B streptococcal infection.

Vitamin B12 Deficiency in Cystic Fibrosis

Sir, In 1983 we reported in your journal (1) a three-year-old girl with very high levels (880 U . Bethesda) of a spontaneously acquired factor VIII inhibitor. We should like to submit two further pieces of information relevant to this case which might be of interest. The antibody was shown to be of IgG type (separation of the proteins and measurement of activated partial thromboplastin time levels with buffer solution containing either IgG or IgM fraction). We also observed a spontaneous decrease in the level of circulating inhibitor and its complete disappearance after four years. The last examination was made 30 November 1984. The patient was in good health and her physical growth progressed normally. There had been no major incident despite persistance of the inhibitor at high levels for such a long period. The disappearance without treatment of the anticoagulant and the clinical wellbeing in absence of serious traumata are two factors which should question the use of immunosuppressors or plasmapheresis except in emergency cases.

Anthony Michael Kent Rickwood

Anthony Michael Kent Rickwood (“Tony”) had a seminal role in establishing paediatric urology as a recognised specialty in the UK and was a founder member of the British Association of Paediatric Urologists in 1990. He was an internationally recognised authority on the paediatric neuropathic bladder. Tony was born on 23 February 1940 in London, where his father was a chemical engineer with ICI. After the war, during which Tony was briefly evacuated to Durham, his family moved to Sheffield, where he spent his childhood and attended King Edward VII School. An outstanding pupil, he won an open scholarship to University College, Oxford, qualifying in medicine in 1965. After junior posts at the Radcliffe Infirmary and a demonstratorship in human anatomy, he returned to Sheffield for his general surgical training at the Royal Hospital. The rotation introduced him to urology, renal transplantation, and paediatric surgery, and in 1974 he started his specialist training in paediatric surgery at Sheffield’s Children’s Hospital. In 1979 Tony was appointed to a newly created consultant post in spinal injuries and spina bifida at Sheffield Children’s Hospital and Lodge Moor spinal injuries unit, where he established an innovative …