Permanent neonatal diabetes mellitus: epidemiology, mode of presentation, pathogenesis and growth.

Permanent neonatal diabetes mellitus (PNIDDM) is a rare form of IDDM with unclear etiology and pathogenesis. We determined the incidence and prevalence rates and studied the clinical and biochemical features of PNIDDM in the Sultanate of Oman. The mean incidence rate during the study period from January 1989 to December 1994 was 1.788 +/- 0.82 per 100,000 live births per year. At the end of December 1994 the prevalence rate was 2.4 per 100,000 children below the age of 5 years. They constituted 41.6% of all cases of IDDM in this age group. Diarrhoea, fever, lethargy, poor feeding and failure to thrive were the most common presenting symptoms. Dehydration and tachypnoea were the most common signs. All patients who developed IDDM during the neonatal period had intrauterine growth retardation and 4.5 presented with diabetic ketoacidosis (plasma glucose 37 +/- 9 mmol/L, pH 7.12 +/- 0.1). Hypertriglyceridemia was a constant feature (19.4 +/- 4.8 mmol/L). They were products of consanguineous marriage with significantly high prevalence of IDDM and NIDDM in their family members. None of the infants had clinical or immunological evidence of congenital viral infection. Three of the five children had HLA-DR2, the diabetes resistance alleles. C-peptide secretion was absent during and after metabolic control of hyperglycemia in all the studied infants and none had circulating islet cell antibody at presentation or during the first year after diagnosis. Despite marked growth retardation at birth, there was a significant improvement of growth after initiating insulin therapy. Four of the 5 patients had normal developmental milestones, one had mild developmental delay following a severe and prolonged attack of hypoglycemia. None of the patients had exocrine pancreatic deficiency. In summary, the very high rate of parental consanguinity, occurrence in both sexes and in two siblings in the same family, absence of islet cell antibodies and the presence of HLA-DR2 loci in 3/5 of patients suggest that PNIDDM is a different disease process to standard IDDM in childhood and an autosomal recessive mode of transmission.

HLA antigen profile in pulmonary tuberculosis patients & their spouses.

HLA-A, -B, -DR and -DQ antigen profile was studied in pulmonary tuberculosis patients (n = 209) and their spouses (family contacts; n = 50) and healthy volunteers (n = 72). An increased frequency of HLA-A-10, B7, B15, DR2 and DQ1 was seen in the pulmonary-TB (PTB) patients when compared to the total control subjects (n = 122). However, a significant increase was seen only with HLA-DR2 (P < 0.001; Pc < 0.01; Relative Risk 2.3) and -DQ1 (P < 0.005; Pc < 0.015; Relative Risk 2.8). Among the spouses and the corresponding patients, a similar increase of HLA-DR2 was seen. A decreased frequency of HLA-A19, B8, B17, B35, DR5 and DR6 were seen in PTB as compared to control groups. The present study suggested that HLA-DR2 and DQ1 genes/gene products may be associated with the susceptibility to tuberculosis either alone or in combination with other HLA or non-HLA genes.

HLA-DR types in rheumatic, congenital and degenerative cardiac valve diseasesin Saudi Patients

Subjects of Saudi origin were DNA typed for HLD-DR2, DR4 and DR[w]53 by fragment-length polymorphism and amplification by sequence-specific primer techniques based on polymerase chain reaction. Of these subjects, 125 sporadic heart valve disease [96 with rheumatic heart disease, 18 with degenerate and 11 with congenital degenerate valve disease] and 77 were healthy Saudi blood donors. While the frequency of individuals typed DR[4] was about the same in the rheumatic heart disease as in the control category [30% versus 23%, respectively], it was found to be higher [55%; P< 0.02], but below the level of marginal significance after correcting for the number of DR types, in the congenital degenerate valve category. No preferential association of any DR4 subtype could be detected. The incidence of DR2 was lower in the congenital cases compared to that in the controls [9% versus 21%] and remained about the same in the rheumatic heart disease patents as in the controls. The frequency of DR[w]53 in the degenerate valve categories was slightly lower than that in the controls, but the difference was not significant. The study failed to corroborate the association between HLA-DR4 and rheumatic heart disease shown in previous studies using the sterotyping approach