Lipoprotein(a) and cardiovascular risk factors in a cohort of 6-year-old children. The Rivas-Vaciamadrid Study

We have studied the distribution of lipoprotein(a) (Lp(a)) and its relation to lipid profiles and a family history of cardiovascular disease in grandparents in a cohort of 673 6-year-old Spanish children. Lp(a) levels were highly skewed, showed no differences between sexes and had no relevant relations with anthropometric variables. When compared with children without a family history of stroke, children with a family history of this disorder showed significantly higher levels of Lp(a) (median 13 mg/dl, range 2–110 mg/dl versus 9 mg/dl, range 2–120 mg/dl, P =0.02). Also the percentage of children with a family history of stroke was higher in the group of children with Lp(a) levels above 30 mg/dl than in the group who exhibited lower levels (20.9% versus 10.4%, P =0.002). Children with a family history of coronary heart disease had higher levels of Lp(a) than children without such history (median 14 mg/dl, range 2–120 mg/dl versus 8 mg/dl, range 2–62 mg/dl, P =0.03). Finally, when compared with children with Lp(a) levels <30 mg/dl, those with Lp(a) levels above 30 mg/dl showed significantly higher mean levels of total cholesterol (174.9 versus 169.4 mg/dl, P <0.05), low-density lipoprotein-cholesterol (109.1 versus 102.4 mg/dl, P <0.05), and apolipoprotein B (81.9 versus 74.6 mg/dl, P <0.05). Conclusion: our study shows the existence of an association between high levels of lipoprotein (a) in 6 year-old children and a family history of both cerebrovascular and coronary disease in grandparents. High levels of lipoprotein (a) were also associated with high levels of low-density lipoprotein-cholesterol and apolipoprotein B.Abbreviations Apo apolipoprotein - LDL low-density lipoprotein - Lp(a) lipoprotein(a)     

Glucose Tolerance in Overweight and Obese North Indian Adolescents

The present analytic study was planned to study the impact of overweight and obesity on glucose tolerance in adolescents. Thirty overweight (BMI analogue ≥ 25–29.9 kg/m²) and 30 obese (BMI analogue ≥ 30 kg/m²) adolescents were included as cases and 30 healthy age and sex matched adolescents comprised the control group. All the study participants were subjected to oral glucose tolerance test (OGTT) as a measure of glucose tolerance.Means of fasting blood glucose levels in normal, overweight and obese groups were 84.5 mg/dl, 86.7 mg/dl and 94.8 mg/dl respectively. Means of two hourly blood glucose levels in normal, overweight and obese groups were 105.8 mg/dl, 117 mg/dl and 127.1 mg/dl respectively. Oral Glucose tolerance test (OGTT) was normal in all the participants from control group but was impaired in four overweight adolescents. In obese group, OGTT was impaired in eight subjects and one obese child had fasting and 2 hourly blood glucose levels in diabetic range.     

Lipid and lipoprotein profiles in children with familial hypercholesterolaemia: effects of therapy

In 71 children with familial hypercholesterolaemia the effect of dietary and/or medical treatment was evaluated. Initial total cholesterol and low density lipoprotein (LDL)-cholesterol levels were significantly lower in children who were consecutively treated by diet (Step-One-Diet) than in those who received additional medication. By dietary treatment, the median total cholesterol level (236.5 mg/dl; range 210–510 mg/dl) was reduced by 7.4% and the median LDL-cholesterol level (162 mg/dl; range 126–423 mg/dl) by 9.9%. By dietary and medical therapy, the median total cholesterol level (330 mg/dl; range 270–424 mg/dl) was reduced by 29.7% and the median LDL-cholesterol level (263 mg/dl; 192–333 mg/dl) by 25.9%. High density lipoprotein (HDL)-cholesterol and HDL 3 remained unchanged. HDL 2 showed a significant decrease of 15.6% up to 27 mg/dl (13–42 mg/dl) on medical treatment. Apolipoprotein A I levels did not change during therapy. Initial apolipoprotein B levels were significantly higher in children who were treated by diet and medication and were reduced by 28.9% by combined therapy. In 28 patients (39.4%) an excess of lipoprotein (a) was detected. Regarding the apolipoprotein E phenotype, 32.2% of the patients carried the risk gene ɛ4 in a hetero- or homozygous form. Conclusion Early dietary and/or medical treatment in hypercholesterolaemic children significantly ameliorates the lipoprotein status. The pretherapy lipoprotein status seems to prognosticate the effectiveness of therapy. Received: 16 April 1997 / Accepted in revised form: 27 May 1998     

Chronic renal failure in a boy with classic Bartter’s syndrome due to a novel mutation in <Emphasis Type="Italic">CLCNKB</Emphasis> coding for the chloride channel

Background  Progressive renal failure in patients with classic Bartter’s syndrome (cBS) due to inactivating mutations in CLCNKB gene is extraordinarily rare. Discussion  We describe a 17-year-old Chinese boy who presented with progressive muscle weakness and renal failure. He was diagnosed as BS of unknown type at the age of 9 months and treated with indomethacin (2 mg/kg/day) and potassium chloride (KCl) supplementation (1.5 mEq/kg/day) for hypokalemia (2.5 mmol/l). At the age of 12 years, serum K⁺ was 3.0 mmol/l and creatinine reached 2.0 mg/dl. On admission, his blood pressure was normal but volume status was depleted. Urinalysis was essentially normal. Biochemical studies showed hypokalemia (K⁺ 2.4 mmol/l) with a high transtubular K⁺ gradient (TTKG) 9.6, metabolic alkalosis (HCO₃ ⁻ 28.4 mmol/l), normomagnesemia (2.0 mg/dl), severe renal failure (BUN 94 mg/dl, Cr 6.3 mg/dl), and hypocalciuria (urine calcium/creatinine ratio 0.02 mg/mg). Abdominal sonography revealed bilateral small size kidneys without nephrocalcinosis or renal stones. After the withdrawal of indomethacin with regular KCl and adequate fluid supplementation for 1 year, serum creatinine and K⁺ levels have been maintained at 4.0 mg/dl and 3.3 mmol/l, respectively. Direct sequencing of NKCC2, ROMK, ClC-Kb, and NCCT in this patient disclosed a novel homozygous missense mutation (GGG to GAG, G470E) in CLCNKB. This G470E mutation was not identified in 100 healthy Chinese subjects. Long-term therapy of non-steroidal anti-inflammatory drugs (NSAIDs), prolonged hypokalemia, chronic volume depletion, and underlying genetic variety may contribute to the deterioration of his renal function. The cautious use of NSAIDs, aggressive correction of hypokalemia, and avoidance of severe volume depletion may prevent the irreversible renal damage in patients with BS due to a Cl⁻ channel defect.     

Extreme hyperbilirubinaemia in Zimbabwean neonates: neurodevelopmental outcome at 4 months

As part of a prospective study of severely jaundiced Zimbabwean infants, the relationship between maximum total serum bilirubin (TSB) concentration in the neonatal period and neurodevelopmental outcome at the corrected age of 4 months was studied. Fifty infants with a TSB of >400 μmol/l (23.4 mg/dl) were enrolled and screened with a neonatal neurological examination (NNE). The cause of jaundice was low birth weight in 22 (44%), ABO incomptability in 8 (16%), sepsis in 8 (16%) and congenital syphilis (6%) in 3 infants. In 9 infants a cause could not be determined. At 4 months, 2 infants had died and 3 were lost to follow up, leaving 45 infants for the infant motor screen (IMS) at 4 months of age. Mean TSB in the neonatal period was 485 μmol/l (28.2 mg/dl), and 7 infants received an exchange transfusion. Mean TSB of the infants with an exchange transfusion was 637 μmol/l (37.2 mg/dl) (range 429–865 μmol/l (25–50.3 mg/dl)) and of the infants without transfusion 459 μmol/l (26.8 mg/dl) (range 400–740 μmol/l (23.4–43 mg/dl)) (P < 0.0001). The TSB was not associated with birth weight, gestational age, gender or head circumference of the baby. On the IMS, 6 of 45 (13.3%) infants scored abnormal, 6 (13.3%) suspect and 33 (73%) scored normal. Three of the six (50%) remaining infants who received an exchange transfusion scored abnormal on the IMS while only 3 of the 39 (8%) infants without exchange transfusion were abnormal. Conclusion More than 25% of infants with a TSB of >400 μmol/l (23.4 mg/dl) scored abnormal or suspect at 4 months of age and half of these infants already showed irreversible neurological symptoms. All infants who scored abnormal or suspect on the IMS with bilirubin levels between 400 and 500 μmol/l (23.4 and 29.2 mg/dl) had haemolytic disease or were premature. Received: 4 October 1996 / Accepted: 5 February 1997     

Clinical data and factors associated with poor outcome in pneumococcal meningitis

We carried out a 4-year study of 159 children (ages 1 month–14 years) with pneumococcal meningitis. The study was divided into two periods: the retrospective period (1998–2000: 107 patients), and the prospective period (2001–2002: 52 patients). About 2/3 of the children were under 2 years of age: 72 (45%) were under 1 year of age and 38 (24%) had meningitis during the second year of life. One-third of the patients had signs of otitis media; convulsions were more frequent in patients under 1 year compared with older patients (34.7 vs. 14.9%; P=0.004); 13/159 children (8.2%) died; 93/159 (58.5%) recovered completely, 12.6% had motor sequelae, 6.9% hydrocephalus, 29.8% sensorineural hearing loss; 140/159 (88%) were treated with third generation cephalosporins, yet only 8.7% of the pneumococci identified were completely penicillin-resistant (≥1 μg/ml); 119/159 were treated with dexamethasone. Four patients had received an injection of heptavalent vaccine. Antibiotics for 1 week prior to admission, shock, abnormal pupils, leukocytes count <6,000 mm³, and CSF glucose ≤8.5 mg/dl were significantly associated with poor outcome and/or death in the univariate analysis. No patient with leukocytosis >16,000/mm³ died. Conclusion. Sequelae are very common in pneumococcal meningitis. Poor outcome was associated with pupillary abnormality and a leukocyte count <6,000/mm³ on admission. Leukocytosis was protective against poor outcome.     

Hypercalciuria is the main renal abnormality finding in Human Immunodeficiency Virus-infected children in Venezuela

Kidney involvement in children with Human Immunodeficiency Virus (HIV) infection is increasing in prevalence in parallel with the longer survival of HIV-infected patients and the side-effects of new antiretroviral drugs. However, there are only a few reports describing renal tubular disorders in HIV+ children. This is a cross-sectional, case series study evaluating kidney disease in 26 Venezuelan HIV-infected children. The study cohort consisted of 15 girls and 11 boys, with a median age of 5.9 years (25–75th percentile: 3.6–7.8), who had been treated with antiretrovirals for 2.8 ± 0.4 years, Overall, the patients were short for their age and gender (Z-height: −3.1; 25–75th percentile: −4.94 to −1.98), and 15 showed signs of mild to moderate malnutrition. All of the children had a normal estimated glomerular filtration rate (136 ± 22.6 ml/min/1.73 m²), and glomerular involvement was only observed in one patient with isolated proteinuria. None had nephromegaly. In contrast, tubular disorders were commonly found. Hypercalciuria was detected in 16 of the patients (UCa/Cr = 0.28; 25–75th percentile: 0.17–0.54 mg/mg), with five of these showing crystalluria. Eight children showed hyperchloremia, and three had frank metabolic acidosis. Kidney stones were absent in all, but one boy had bilateral medullary nephrocalcinosis. Conclusion, in Venezuelan children, HIV infection per se, or its specific treatment, was commonly associated with renal tubular dysfunction, especially hypercalciuria and acidosis, potentially leading to nephrocalcinosis and growth impairment. We recommend renal tubular evaluation during the follow-up of children with HIV infection.     

Neurodevelopmental outcome at 1 year in Zimbabwean neonates with extreme hyperbilirubinaemia

The study concentrates on estimating the magnitude of the effect of a single risk factor, maximum total serum bilirubin (TSB) in excess of 400 μmol/l (23.4 mg/dl), on the neurodevelopmental outcome of 50, singleton, Zimbabwean neonates at 1 year of age. At 1 year corrected age the Bayley Scales of Infant Development (BSID) was administered. Two infants died and five were lost to follow up. TSB was neither associated with birth weight nor with gestational age. Of 43 infants with a TSB >400 μmol/l (23.4 mg/dl),11(26%) scored abnormal on the BSID at 1 year of age and 5 (12%) infants developed the choreo-athetoid type of cerebral palsy. Conclusion Infants with bilirubin levels between 400 and 500 μmol/l (23.4 and 29.2 mg/dl) who scored abnormal or suspect on the Bayley Scales of Infant Development were preterm or had haemolytic disease. All term infants without haemolysis and with bilirubin levels between 400 and 500 μmol/l (23.4 mg/dl–29.2 mg/dl) were normal at 1 year of age. Received: 19 February 1998 / Accepted: 22 June 1998     

Helicobacter pylori infection in postoperative patients with biliary atresia A benign colonization?

The prevalence of Helicobacter pylori infection in postoperative patients with biliary atresia (BA) was investigated in relation to esophageal varices, portal-hypertensive gastropathy (PHG), and peptic ulcer disease (PUD) in 25 Japanese patients (10 boys and 15 girls) aged from 16 months to 20 years. Gastric biopsy specimens obtained during endoscopy were used for both the rapid urease test and modified Giemsa staining. The patients were classified into three groups according to liver function: 15 in group A (total bilirubin [TB] < 1.0 mg/dl), 7 in group B (1.0 ≤ TB < 2.0 mg/dl), and 3 in group C (TB ≥ 2.0 mg/dl). Esophageal varices were found in 19 patients (60% of group A and all patients in groups B and C) and PHG in 3 group B patients. However, no gastric or duodenal ulcers were found in any case. Only 2 patients (8%) had H. pylori colonization of the gastric mucosa. Both, however, belonged to group A, and the degree of chronic neutrophilic infiltration of the mucosal layer was as mild as that of the other patients. The prevalence of H. pylori infection and PUD in postoperative patients with BA was quite low, and a pathological relationship with the severity of liver disease could not be determined in these patients. Accepted: 2 December 1998     

The prevalence and etiology of anemia among HIV-infected children in India

In this report, the prevalence and multifactorial etiology of anemia among Indian human immunodeficiency virus (HIV)-infected children are described. HIV-infected children aged 2–12 years were prospectively enrolled in 2007–2008. Measured parameters included serum ferritin, vitamin B₁₂, red-cell folate, soluble transferrin receptor, and C-reactive protein. Children received antiretroviral therapy (ART), iron and, folate supplements as per standard of care. Among 80 enrolled HIV-infected children (mean age 6.8 years), the prevalence of anemia was 52.5%. Etiology of anemia was found to be iron deficiency alone in 38.1%, anemia of inflammation alone in 38.1%, combined iron deficiency and anemia of inflammation alone in 7.1%, vitamin B₁₂ deficiency in 7.1%, and others in 9.5%. Median iron intake was 5.7 mg/day (recommended dietary allowance 18–26 mg/day). Compared to nonanemic children, anemic children were more likely to be underweight (weight Z-score −2.5 vs. -1.9), stunted (height Z-score −2.6 vs. -1.9), with lower CD4 counts (18% vs. 24%, p < 0.01), and higher log viral load (11.1 vs. 7.1, p < 0.01). Hemoglobin (Hb) improved significantly among those who started ART (baseline Hb 11.6 g/dl, 6-month Hb 12.2 g/dl, p = 0.03). Children taking ART combined with iron supplements experienced a larger increase in Hb compared to those receiving neither ART nor iron supplements (mean Hb change 1.5 g/dl, p < 0.01). Conclusion Anemia, particularly iron deficiency anemia and anemia of inflammation, is highly prevalent among children with HIV infection. Micronutrient supplements combined with ART improved anemia in HIV-infected children.     

Free fatty acids and triglycerides in normoglycemic low birth weight newborns in early neonatal period

Free fatty acids, triglycerides and blood sugar were estimated in 45 lowbirth weight which included 24 preterm and 21 small for gestational age term babies, in the cord blood, in the fasting state at 6±1 h of age, and after initiation of sugar water feeds at 24±2 h of age. Thirty six appropriate for gestational age, term newborns were taken as controls. None of the newborns were born to diabetic mothers or had hypoglycemia. Mean cord blood sugar levels in all the groups were similar ranging between 69.55 to 73.7 mg/dl. followed by a fall in all at 6±1 h and subsequent rise at 24±2h. levels were significantly lower in LBW newborns compared to controls. Means FFA levels were lowest in babies with agestation of 28–32 weeks (0.27 m Mol/L), being almost similar to controls (0.35 mMol/L) in preterm 33–36 weeks (0.32 mMol/L) and higher than controls in SGA (0.48 mMol/L). An inverse relationship with blood sugar level was seen in serial estimations. SGA neonates continued to show higher and preterm (28–32 weeks) lowest levels throughout the study period. Triglycerides in cord blood were 36.72 mg/dl, 38.33 mg/dl, 56.23 mg/dl and 40.11 mg per cent in preterm 28–32 weeks, 33–36 weeks, SGA term and controls respectively. Levels showed a steady rise during the study period.     

Treatment with a gonadotropin-releasing-hormone analog and attainment of full height potential in a male monozygotic twin with gonadotropin-releasing hormone-dependent precocious puberty

We report on a pair of male monozygotic twins, one unaffected and the other affected with gonadotropin-releasing hormone (GnRH)-dependent precocious puberty, and discuss the role of treatment with a GnRH analog in the attainment of full height potential in GnRH-dependent precocious puberty. At 1.6 years of age, the affected twin was studied for tall stature (+3.8 SD), and was diagnosed as having GnRH-dependent precocious puberty due to a hypothalamic hamartoma of the tuber cinereum. He was treated with oral cyproterone acetate (110–170 mg/m² daily) from 1.8 through 5.0 years of age, with oral cyproterone acetate and intranasal buserelin acetate (700–900 μg/m² daily) from 5.0 through 7.5 years, and with intranasal buserelin acetate alone (1100– 1400 μg/m² daily) from 7.5 through 12.6 years. He attained a final height of 171.0 cm at 14.9 years of age (+0.10 SD) and his twin 170.0 cm at 15.3 years of age (−0.10 SD), with their target height being 174.5 ± 9.0 cm. Conclusion This study indicates that GnRH analog treatment may preserve near full height potential in some patients with GnRH-dependent precocious puberty. Received: 30 March 1999 / Accepted: 31 May 1999     

Enalapril in paediatric patients with Alport syndrome: 2 years' experience

Enalapril, a long-acting inhibitor of angiotensin-converting enzyme, was given for 2 years to seven children with Alport syndrome. Five patients had a classical X-linked form of the disease; two siblings had the autosomal recessive variant. Their age was between 5.15 and 13.75 years when enalapril was started. All patients had haematuria and proteinuria, creatinine clearance was >80 ml/min per 1.73 m² in all, and only one patient was hypertensive. The starting dose of enalapril (0.1 mg/kg body weight per day) was increased progressively according to individual clinical tolerance. The median doses were 0.13, 0.12, 0.21 and 0.29 mg/kg at 6, 12, 18 and 24 months, respectively. Median values of mean blood pressure were 95 mmHg at the start and 84 mmHg after 24 months. Median daily proteinuria decreased from 52 mg/kg to 18 mg/kg at 6 months, 21 mg/kg at 12 months, 12 mg/kg at 18 months and 30 mg/kg at 24 months. Serum creatinine increased over time from a median of 0.64 mg/dl at baseline to 0.77 mg/dl at 24 months. Concomitantly, there was a decrease in GFR from 104 to 83 ml/min per 1.73 m² at 18 months and an increase again to 95 ml/min per 1.73 m² at 24 months. Analysis of the individual data showed three patterns: no response (n=2), temporary response (n=2) and sustained response (n=3). Conclusion When given enalapril at the dosages mentioned, Alport patients as a group display a marked reduction in urinary protein excretion with a nadir of 23% of the baseline figure at 18 months, a decrease that cannot be accounted for by the slight decrease in glomerular filtration rate. Although these are preliminary data, it is recommended to try an angiotensin-converting enzyme inhibitor in every paediatric Alport patient with proteinuria. Received: 27 September 1999 and in revised form 6 December 1999 / Accepted: 6 December 1999     

Transepidermal water loss and cerebral hemodynamics in preterm infants: conventional versus LED phototherapy

The aim of our study was to evaluate whether high-intensity gallium nitride light-emitting diode (LED) phototherapy (LPT) influences transepidermal water loss (TEWL) and cerebral hemodynamics in preterm neonates in comparison with conventional phototherapy (CPT). Thirty-one preterm infants were randomized for conventional (n = 14) and for LED (n = 17) phototherapy. All infants were studied using a Tewameter TM 210 and cerebral Doppler ultrasound immediately before phototherapy (time 0), 30 min (time 1), 1–6 h (time 2), and 12–24 h (time 3) after the start of phototherapy, and 6–12 h after discontinuing phototherapy (time 4). The study shows that LPT does not induce significant changes in TEWL (time 0: 2.75 ± 4.71 ml/m²/h; time 3: 14.45 ± 3.68 ml/m²/h), in peak systolic, end diastolic and mean cerebral blood flow velocity (CBFV), and in the resistence index (RI). On the contrary, CPT is associated with a significant increase of TEWL (time 0: 13.22 ± 5.61 ml/m²/h; time 3: 20.94 ± 3.21 ml/m²/h), which disappeared at time 4, when phototherapy had stopped. The peak systolic and mean CBFV increased, respectively, from 0.11 ± 0.03 m/s at time 0 to 0.16 ± 0.07 m/s at time 3. We conclude that LPT, emitting light within the 450–470-nm spectrum for optimal bilirubin degradation, can be preferable to CPT for the therapy of hyperbilirubinemia in preterm infants.     

Plasma levels of interleukin-6 and interleukin-10 in preterm neonates evaluated for sepsis

In a prospective study, plasma interleukin-6 (IL-6) and interleukin-10 (IL-10) levels were measured by enzyme-linked immunosorbent assay in 45 premature neonates (25–34 weeks gestational age) with signs and symptoms of suspected sepsis at 0, 12 and 24 h; C-reactive protein (CRP) was measured at 0–24 h after enrolment. Six subjects were excluded due to insufficient blood sampling. The remaining 39 neonates were assigned to one of three groups: 25 newborns with sepsis (blood culture positive), seven with pneumonia (positive results on broncho-alveolar lavage fluid culture and characteristic chest radiography) and seven with necrotising enterocolitis (NEC) (characteristic intestinal and radiological signs according to the criteria of Bell et al.). A group of 20 healthy preterm neonates represented control subjects. On admission, higher levels of IL-6, IL-10 and CRP were observed in neonates with sepsis: IL-6 (median 1500 pg/ml, range 487–10000 pg/ml), IL-10 (median 113 pg/ml, range 70–196 pg/ml), CRP (median 22 mg/l, range 4–80 mg/l); pneumonia: IL-6 (median 1500 pg/ml, range 747–8000 pg/ml, IL-10 (median 84 pg/ml, range 76–92 pg/ml), CRP (median 10 mg/l, range 8–33 mg/l) and NEC: IL-6 (median 6650 pg/ml, range 1595–7950 pg/ml), IL-10 (median 80 pg/ml, range 61–147 pg/ml), CRP (median 3 mg/l, range 2.8–8 mg/l) as compared to controls (IL-6 median 208 pg/ml, range 198–349 pg/ml; IL-10 median 36 pg/ml, range 19–50 pg/ml; CRP median <2 mg/l) (P < 0.05). In neonates with sepsis, IL-6 levels were significantly correlated with IL-10 levels (r=0.65; P=0.04) at the time of the second sample. The highest IL-6 levels were observed at onset, while IL-10 was predominant 12 h later. On admission, IL-10 and CRP levels were significantly higher in non-survivors (IL-10 median 507 pg/ml, range 422–753 pg/ml; CRP median 123 mg/l, range 20–219 mg/l) than in survivors (IL-10 median 76 pg/ml, range 61–143 pg/ml; CRP median 8 mg/l range 3–46 mg/l), while IL-10 levels were significantly higher (P < 0.05) also 12 h after admission (non-survivors: IL-10 median 600 pg/ml, range 538–800 pg/ml; survivors: IL-10 median 74 pg/ml, range 53–161 pg/ml). IL-6 and IL-10 levels were significantly correlated with CRP levels on admission (r=0.45; P=0.05). Conclusion Preterm neonates with sepsis, pneumonia or necrotising enterocolitis showed increased interleukin-6, interleukin-10 and C-reactive protein levels. High interleukin-10 concentration was associated with mortality and could be an early indicator of prognosis. Received: 21 November 2000 / Accepted: 23 January 2001     

Hyperinsulinaemic hypoglycaemia associated with persistent hyperammonaemia

Two cases of hyperinsulinaemic hypoglycaemia associated with persistent hyperammonaemia in unrelated infants of 7 days and 4 months of age are reported. Blood ammonia levels were 100–300 μmol/l (normal values<40 μmol/l). The hyperammonaemia was asymptomatic and not associated with any of the abnormalities of amino acids or organic acids observed in urea cycle enzyme defects. Orotic aciduria was normal. The hyperammonaemia was not influenced by the levels of blood glucose nor by subtotal pancreatectomy. On admission blood glucose was ca. 1.2 mmol/l (21.6 mg/dl) corresponding to blood insulin levels of 35 and 22 mU/l respectively in both infants. Continuous intravenous glucose perfusion was necessary to prevent hypoglycaemia. Furthermore 2-oxoglutaric acid in urine was increased in the second infant to 3.15 mg/mg creatinine (normal 0.41 +/−0.12). This may point to mutations in the glutamate dehydrogenase gene. Conclusion 2-Oxoglutaric aciduria may be an important clue to the diagnose in this syndrome. Received: 6 January 1998 / Accepted: 25 November 1998     

Insulin resistance is associated with at least threefold increased risk for prothrombotic state in severely obese youngsters

Obesity in childhood increases the risk for early adult cardiovascular disease. However, the underlying mechanism is not fully known. The aims of this study were to measure levels of prothrombotic factors and examine their possible association with obesity and insulin resistance in obese children and adolescents. A total of 313 obese children and adolescents were recruited. In a cross-sectional design, we measured anthropometric parameters, plasminogen activator inhibitor-1-antigen (PAI-1-Ag), von Willebrand factor-antigen (vWF-Ag), fibrinogen (FB), lipids, fasting glucose, and insulin (FI) levels. Insulin resistance was estimated using the homeostasis model assessment for insulin resistance (HOMA-IR) index. Boys presented significantly higher PAI-1-Ag levels than girls (82.6 vs. 71.3 ng/ml, p = 0.01). Higher levels of PAI-1-Ag (96.8 vs. 69 ng/ml, p < 0.001), vWF-Ag (123.5 vs. 107.6%, p = 0.004) but not FB (353.1 vs. 337.6 mg/dl, p = 0.137) were found in insulin-resistant (IR) participants after adjusted for age, gender, and pubertal stage. IR patients were at 2.98 (CI: 1.084–8.193) and 4.86 (CI: 1.119–15.606) times greater risk for high PAI-1-Ag and vWF-Ag levels, respectively. All three prothrombotic factors were positively correlated with body mass index (BMI) and FI levels (p < 0.05), but only PAI-1-Ag and vWF-Ag were significantly correlated with HOMA-IR index (p ≤ 0.001). After adjustment for confounding factors, both BMI and HOMA-IR indices remained significantly associated with PAI-1-Ag (r ² = 0.225, p < 0.001) and vWF-Ag levels (r ² = 0.077, p = 0.003). Conclusion: This study shows that obesity in youngsters, when accompanied with insulin resistance, is associated with at least threefold increased risk for elevated levels of prothrombotic factors, contributing to the early development of atherothrombosis. This impaired prothrombotic state may partially explain the increased risk for developing cardiovascular disease later in adulthood.     

Lipid profile in the progeny of parents with ischemic heart disease

Lipid profile of 50 offsprings of parents with ischemic heart disease and 15 control children aged 5–16 years was studied. The children in both the groups were categorized into 3 sub groups, 5–10, 11–15 & >15 years. The Serum total cholesterol levels (mean ±S.D.) (in mg/dl) in the test group were 169.8±15.13, 173.34±33.56, 177.4±27.89 respectively for the 3 age subgroups. The Serum LDL cholesterol levels (mean ±S.D) (in mg/dl) in the test group were 102.2±15.25, 95.13±30.38, 101.09±26.96 respectively. The serum total cholesterol levels (mean ±S.D) (in mg/dl) in the control group were 123±1.33, 118±7.51 and 127.4±5.77 respectively for the 3 age subgroups. The serum LDL cholesterol levels (mean +S.D) (in mg/dl) in the control group were 56.64±8.75, 43.36±6.10 and 45.16±6.78 respectively. The serum total cholesterol and LDL cholesterol levels in the test group were significantly higher as compared to controls (p>0.05). Among test subjects, 54% had elevated total cholesterol (>170 mg/dl) and 38% had elevated LDL cholesterol (>110 mg/dl). These cases had a significant correlation with elevated parental total cholesterol and LDL cholesterol levels (p>0.05). Thus, a selective screening of the offsprings of parents with premature ischemic heart disease and hypercholesterolemia is advocated.     

Galactose metabolites in blood from neonates with and without hypergalactosaemia detected by mass screening

Concentrations of galactose (Gal) in plasma and galactose metabolites in red blood cells (RBC) were determined in 18 normal neonates and 249 others with hypergalactosaemia according to the Paigen method. Normal neonatal values for plasma Gal, RBC galactose-1-phosphate (Gal-1-P), RBC uridine diphosphate glucose (UDP-Glc), and RBC uridine diphosphate galactose (UDP-Gal) were 0.96 ± 0.71 mg/dl, 1.69 ± 1.45 mg/dl of packed RBC, 1.00 ± 0.45 mg/dl of packed RBC, and 1.44 ± 0.45 mg/dl of packed RBC, respectively. The UDP-Gal concentration was higher and the UDP-Glc concentration lower than previously reported in normal children. Of the 249 cases with excessive Gal in whole blood, 23 showed high Gal concentrations in plasma; among these, four portacaval shunts and one case of congenital biliary atresia were diagnosed. In subjects homozygous or heterozygous for UDP-Gal-4 epimerase deficiency, concentrations of UDP-Gal and Gal-1-P were elevated only in RBC, corresponding to restriction of the metabolic abnormality to these cells. Most cases of hypergalactosaemia detected by the Paigen method have large excesses of Gal-1-P in RBC. Although a specific diagnosis based solely on blood Gal metabolites is difficult, individual concentrations reflect underlying conditions to some extent. Conclusion In neonates, uridine diphosphate galactose concentrations were higher and uridine diphosphate glucose concentrations were lower than previously reported paediatric values. Patients with high plasma galactose concentrations should be investigated by hepatic imaging. Received: 21 March 2000 / Accepted: 18 May 2000     

Effect of central precocious puberty and gonadotropin-releasing hormone analogue treatment on peak bone mass and final height in females

To evaluate the effect of central precocious puberty (CPP) and its treatment with gonadotropin-releasing hormone (GnRH) analogues on final height and peak bone mass (PBM), we measured lumbar bone mineral density (BMD) in 23 girls at final height. Patients were distributed in two groups. Group 1: 14 patients with progressive CPP were treated with GnRH analogues; seven patients received buserelin (1600 μg/daily), subsequently switched to depot triptorelin (60 μg/kg/26–28 days); seven patients were treated with depot triptorelin (60 μg/kg/26–28 days); mean age of treatment was 6.2 years (range 2.7–7.8 years); the treatment was discontinued at the mean age of 10.1 years (range 8.7–11.3 years); final height was reached at the mean age 13.4 years (range 12.0–14.9 years). Group 2: 9 patients (mean age 6.5 years, range 4.8–7.7 years) with a slowly progressing variant of CPP were followed without treatment; final height was reached at the mean␣age␣13.6 years (range 12.5–14.8 years). Lumbar BMD (L₂-L₄ by dual energy X-ray␣absorptiometry) was measured in all patients at final height. In group 1, final height␣(158.9 ± 5.4 cm) was significantly greater than the pre-treatment predicted height (153.5 ± 7.2 cm, P < 0.001), but significantly lower than mid-parental height (163.2 ± 6.2 cm, P < 0.005). Subdividing the girls of group 1 according to the bone age at discontinuation of therapy (i.e. ≤11.5 years, n = 5, or ≥12.0 years, n = 9), the former patients had a final height significantly higher than the latter (163.7 ± 3.9 cm vs 156.5 ± 4.6 cm, P < 0.02). In group 2, final height (161.8 ± 4.6 cm) was similar to the pre-treatment predicted height (163.1 ± 6.2 cm, P = NS) and was not significantly different from mid-parental height (161.0 ± 5.9 cm). BMD values (group 1: 1.11 ± 0.14 g/cm², group 2: 1.22 ± 0.08 g/cm²) were not significantly different from those of a control group (1.18 ± 0.10 g/cm²; n = 20, age 16.3–20.5 years) and the patients' mothers (group 1: 1.16 ± 0.07 g/cm², n = 11, age 32.9–45.1 years; group 2: 1.20 ± 0.08 g/cm², n = 7, age 33.5–46.5 years). In group 1, the girls who stopped therapy at a bone age ≤11.5 years had significantly higher BMD (1.22 ± 0.10 g/cm²) compared to those who discontinued therapy at a bone age ≥12.0 years (1.04 ± 0.12 g/cm², P < 0.05). Conclusion In girls with progressive CPP, long-term treatment with GnRH analogues improves final height. A subset of patients with CPP does not require treatment because good statural outcome (slowly progressing variant). In CPP, the abnormal onset of puberty and the long-term GnRH analogue treatment do not impair the achievement of PBM. In GnRH treated patients, the discontinuation of therapy at an appropriate bone age for pubertal onset may improve both final height and PBM. Received: 5 June 1997 / Accepted in revised form 21 November 1997