We prosepctively studied 200,000 newborns to determine the frequency and clinical characteristics of alpha1-antitrypsin deficiency. One hundred and twenty Pi Z, 48 Pi SZ, two PI Z-and one Pi S-infants were identified and followed to the age of six months. Fourteen of 120 Pi Z infants had prolonged obstructive jaundice, nine with severe clinical and laboratory evidence of liver disease. Five had only laboratory evidence of liver disease. Eight other Pi Z infants had minimal abnormalities in serum bilirubin and hepatic enzyme activity and variable hepatosplenomegaly. All 22 Pi Z infants with hepatic abnormalities, two thirds of whom were made, appeared healthy at six months of age. Ninety-eight Pi Z infants did not have clinical liver disease, but liver-function tests gave abnormal results in 44 of 84 at three months, and in 36 of 60 at six months of age. The number of small-for-gestational-age infants was greater (P less than 0.001) among those with clinical liver disease. None of the 48 Pi SZ infants had clinical liver disease, but 10 of 42 at three months and one of 22 at six months of age had abnormal liver function. The Pi Z and Pi SZ phenotypes are associated with covert or readily apparent hepatic dysfunction in the first three months of life.

During 1972-1974, 200,000 Swedish infants were screened for alpha 1-antitrypsin deficiency. Of 127 PiZ (Protease inhibitor) children followed from infancy to 12 years of age, four PiZ children with neonatal liver disease have died; two of liver cirrhosis, one was found to have liver cirrhosis at autopsy, having died of aplastic anemia and the fourth died in an accident. Liver microscopy showed a mild increase of periportal fibrous tissue. Another PiZ child died of anaphylactic shock. At 12 years of age, none of the PiZ children have clinical symptoms of liver disease. No PiZ-, PiSZ, PiS- or PiFZ child has had any clinical symptom of liver disease. One PiSZ child died of sudden infant death syndrome. Laboratory analyses from birth through 12 years of age have shown increased S-Bilirubin levels in 11% of the PiZ infants, which normalized within the first half year of life. S-GT was abnormal in about half of the infants, but had normalized when checked at 8 and 12 years of age in all but 6-3% of the PiZ children. The percentage of abnormal S-ALAT test results have decreased from 73% during the first year of life, to about 15% at the age of 12. The range of the abnormal levels also decreased considerably. Abnormal S-GT or S-ALAT levels were found in about 20% of the PiSZ infants, the proportion decreasing to 2% at the age of 12.

Of 200,000 Swedish infants screened for alpha 1-antitrypsin deficiency (alpha 1 ATD), 184 (127 PiZ, 2 PiZ-, 54 PiSZ, and 1 PiS-) children have been followed prospectively, of whom 1 PiSZ and 5 PiZ children died in early childhood. We now report clinical and biochemical signs of liver disease in adolescence and the prognosis of neonatal liver disease up to the age of 18 years. The alpha 1 ATD subjects were offered a clinical checkup and liver tests at 16 and 18 years of age, 150 of 178 alpha 1ATD subjects undergoing checkups at age 16 and 166 at age 18. Liver tests were performed in 121 adolescents at both the 16- and 18-year checkups. None of the PiZ and PiSZ subjects checked at the age of 16 and 18 years had any clinical signs of liver disease. Abnormalities of serum alanine aminotransferase (S-ALAT) or gamma-glutamyl transferase (S-GT) were found at the 16-year checkup (all PiZ and PiSZ subjects tested included) in 17% of PiZ and 8% of PiSZ adolescents, and at the age of 18 years in 12% of PiZ and 15% of PiSZ subjects. In only two cases were both S-ALAT and S-GT concentrations abnormal at both the 16-year and 18-year follow-ups. Serum procollagen III peptide concentrations were normal in all those with abnormal liver test results. Of 127 PiZ subjects, 22 had manifested clinical signs of liver disease in infancy. Of these 22, two died early in life of cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiological studies have indicated a relationship between overweight and cardiovascular disease. The present investigation was undertaken to identify anthropometric variables in childhood which may reflect the risk of cardiovascular disease in terms of unfavourable changes in apolipoprotein and lipid concentrations. Twenty-nine obese 14-year-olds and 32 obese 12-year-olds were recruited from a school screening programme and anthropometric data reflecting overweight and fat distribution were subjected to analysis of covariance, with blood pressure, apolipoprotein and lipid concentrations as dependent variables. Results from the two groups were adjusted for puberty, gender and screening group, allowing pooling of data. After such an adjustment, waist circumference was significantly correlated (r = partial correlation coefficient) to high density lipoprotein (HDL) cholesterol (r = -0.08, p < 0.05) and triglycerides (r = +0.24, p < 0.01). The waist:hip ratio was significantly correlated to HDL-cholesterol (r = -0.10, p < 0.01) and triglycerides (r = +0.22, p < 0.01). BMI was significantly correlated to triglycerides (r = +0.25, p < 0.001), and diastolic blood pressure (r = +0.08, p < 0.05). The partial regression coefficients for waist circumference versus apolipoprotein B (r = +0.07) and the apolipoprotein B:A-I ratio (r = +0.06) were as strong as those for waist:hip ratio (r = +0.03 and r = +0.05, respectively). Our results demonstrate that abdominal obesity is associated with an unfavourable lipid profile in obese 12-14-year-old children. This may be related to an increased cardiovascular risk later in life. The waist measurement appears to be a convenient and informative anthropometric indicator of such metabolic alterations.

At the age of 30, the AAT-deficient individuals in this cohort report more symptoms than the control subjects. Smoking is less common in the cohort compared to controls. Their lung function is normal.