PATIENTS AND METHODS: We report two siblings of a healthy but consanguineous Malaysian family presenting with severe short stature caused by CPHD with a variable phenotype. Importantly, at the beginning the girl presented with isolated GHD, whereas the boy was hypothyroid. As the most common gene alterations responsible for CPHD are within either the PROP-1- or the POU1F1- (PIT-1)-gene these two genes were further studied.
RESULTS: Subsequent sequencing of the six exons of the POU1F1-gene allowed the identification of a new N-terminal mutation (Q4ter) in these two children. A substitution of C to T induced a change from a glutamine (CAA) to a stop codon (TAA) in exon 1 of the PIT-1 protein. Both affected children were homozygous for the mutation, whereas the mother and father were heterozygous.
CONCLUSION: We describe two children with autosomal recessive inherited CPHD caused by a new N-terminal located mutation within the PUO1F1-gene. The clinical history of these two children underline the phenotypic variability and support the fact that children with any isolated and/or combined PHD need to be closely followed as at an any time other hormonal deficiencies may occur. In addition, molecular analysis of the possible genes involved might be most helpful for the future follow-up.
METHODS: Age-standardized mortality rates were calculated for 16 amenable causes of death in Singapore for six 5-year periods (1965-1969,..., 1990-1994), and for each of the three main ethnic groups for three periods (1989-1991, 1992-1994, 1995- 1997). Amenable mortality rates were divided into those which can be reduced by timely therapeutic care for 'treatable' conditions (e.g. asthma and appendicitis), or by primary preventive measures for 'preventable' conditions (e.g. lung cancer and motor vehicle injury).
RESULTS: Amenable mortality was higher in males (age-standardized rate 109.7 per 100 000 population) than in females (age-standardized rate 60.7 per 100 000 population). Amenable mortality declined by 1.77% a year in males and 1.72% a year in females. By comparison, the average yearly decline in non-amenable mortality was 0.91% in males and 1.17% in females. The decline in amenable mortality was largely due to 'treatable' causes rather than a decline in mortality due to 'preventable' causes of death. Amenable mortality was lowest for Chinese and highest for Malays. Over the recent 9-year period from 1989 to 1997, amenable mortality declined more in Chinese than in Malays and Indians. However, Indian females showed by far the sharpest decline, whereas Indian males, by contrast, showed an increase in amenable mortality, due to both treatable and preventable causes.
CONCLUSIONS: In line with findings from European countries, amenable mortality in Singapore declined more than non-amenable mortality. There were more significant gains in mortality outcomes from medical care interventions than from primary preventive policy measures. Gender and ethnic differences in amenable mortality were also observed, highlighting issues of socioeconomic equities to be addressed in the financing and delivery of health care.
METHODS: A study of all patients with significant GOER seen at the Paediatric Gastroenterology Unit, Queen Elizabeth Hospital for Children, Hackney Road, London, between December 1994 and August 1995.
RESULTS: The median age at referral was 16 months. Presenting symptoms were recurrent vomiting (72%), epigastric and abdominal pain (36%), feeding difficulties (29%), failure to thrive (28%) and irritability (19%). Continuous 24-h lower oesophageal pH studies performed in 57 children showed 20 (35%) had a reflux index of between 10% to 20%, 14 (25%) had a index > 20%, and six (11%) had a postprandial reflux index > 10%. Reflux was shown in 38 (62%) of 62 children who underwent barium studies. None had significant anatomical abnormalities, but in the 22 children who had a negative barium studies, six had severe reflux (reflux index > 20%). Upper gastrointestinal endoscopy performed in 47 children showed reflux oesophagitis in 29 (62%), oesophageal ulceration in three, and Barrett's oesophagus in one. All of the children were treated with standard medical therapy. Sixty-six per cent were able to discontinue medication within 12 months and remained well. Four children (6%) required Nissen's fundoplication for failure to respond to medical therapy.
CONCLUSIONS: Most infants with GOER have an uncomplicated course. False negative results were noted in both pH monitoring and barium meal. Up to 80% of children, with therapy, will improve within 12 months.