The effect of oral calcium carbonate administration on serum lipoproteins of children with familial hypercholesterolaemia (type II-A)

The effect of oral calcium carbonate on serum lipoprotein concentrations was tested in 50 children with familial hypercholesterolemia (type II-A) consuming a low cholesterol high polyunsaturated fat diet, using a cross-over design versus a placebo. Cholesterol was measured in serum and in the individual lipoprotein density classes. Serum apolipoprotein B (the protein moiety of low density lipoprotein) and apolipoprotein A-I (the main protein of high density lipoprotein) were measured by specific immunoassays. Calcium carbonate treatment induced only a slight increase in serum apolipoprotein A-I (+4%) and a slight decrease in low density lipoprotein cholesterol (-4%), both changes being significant at the P=0.05 level.     

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     

Screening for congenital hypothyroidism in Turkey

Abstract A pilot study was performed to determine the incidence of congenital hypothyroidism (CH) in Turkey and to build a model for nationwide screening. From December 1991 to December 1992, 30097 newborns were screened for CH using a primary measurement of thyroid stimulating hormone in capillary blood on days 3–5 of life. Samples were obtained in collaboration with the ongoing nationwide phenylketonuria screening programme. Eleven cases of primary CH were detected giving the incidence of 12736. Recall rate was 2.3%. Replacement therapy withl-thyroxine was started after the confirmation of diagnosis. The median age at the initiation of replacement therapy was 23 days (range 7–35 days).Conclusion The incidence of CH is notably higher in Turkey than reported in most other countries. Iodine deficiency and/or dyshormonogenesis might contribute to this high incidence. This result emphasizes the necessity of a nationwide screening programme.     

Pinpoint skin lesions in a familial hypercholesterolaemia homozygote

The case is reported of a 2-y-old girl referred to the outpatient lipid clinic because of a tiny cutaneous xanthoma on the dorsum of the left foot and a family history of hyperlipidaemia and coronary heart disease (CHD). Fasting serum total cholesterol levels were remarkably high (27.1 mmol l(-1), 1050 mg dl(-1)) and DNA analysis confirmed homozygous familial hypercholesterolaemia (class II mutation). Serum lipids were not affected by dietary intervention and cholestyramine treatment, so low-density lipoprotein apheresis was scheduled to commence at the age of 4 y. Conclusion: An early lipid profile determination should be performed in children with a family history of premature CHD, since the physical examination may be unremarkable even in cases of severe hyperlipidaemia during the first years of life.     

Neonatal Screening for Cystic Fibrosis by Dried Blood Spot Trypsin Assay

47127 newborn infants from the Emilia-Romagna region were screened for cystic fibrosis by dried blood spot trypsin assay. In the initial 12099 subjects screened with a non-standardized method, two children with cystic fibrosis were observed. Of the remaining 35028 newborn infants, 299 showed high immunoreactive trypsin values; retesting revealed persistent elevation in 11. Sweat testing confirmed cystic fibrosis in 6 subjects and was normal in 5. Clinical monitoring of these 5 children has, as yet, shown no pathological signs. No false-negative test results have yet been identified. In our region, cystic fibrosis frequency would appear to be 1 case every 5890 newborn infants. Our study confirms that elevated immunoreactive trypsin is characteristic of newborn infants with cystic fibrosis and that screening by determination of immunoreactive trypsin is of great benefit since it allows early diagnosis and a rational approach to therapy.     

Evaluation of neonatal BH4 loading test in neonates screened for hyperphenylalaninemia

Background

The outcome in phenylketonuria is related to the early diagnosis and management due to neonatal screening.

Aims

To assess the interest of tetrahydrobiopterin (BH4) loading test and phenylalanine hydroxylase (PAH) genotyping in the management of neonates with hyperphenylalaninemia (HPA).

Study design

We evaluate the effectiveness of a BH4 loading test (20 mg/kg) in ten neonates screened for HPA. We evaluated the time required to reach a target plasma Phenylalanine (Phe) level below 300 µmol/l. We compared these ten BH4-loaded patients to the 10 previous neonates non-loaded with BH4. In all these patients, the PAH genotype was determined.

Results

One loaded patient had biopterin synthesis deficiency and has been retrieved from statistical analysis. All others patients have PAH deficiency. Between the BH4 loaded group (L) and the BH4 non-loaded group (NL), a statistically significant difference was observed in the average time required to reached the target Phe level (13.56 ± 4.30 (L) vs. 20.6 ± 7.59 days (NL) [p < 0.02]). Results of the genotyping from all but one of these 19 patients indicated that among all mutations present in this patient population, there were 4 known PAH mutations associated with BH4 responsiveness (p.R261Q, the p.V388 M, the p.E390G and the p.Y414C). These mutations were found in 4 non-loaded and 6 loaded patients. Two patients had a more than 90% reduction in their plasma Phe level within 24 h after the load. One of these patients had a PTPS deficiency. The other fully responsive patient (p.Y414C and IVS10-11G > A) has been treated with BH4 from birth with an excellent metabolic control for three years now.

Conclusion

BH4 loading test improves the management of HPA. It allows an immediate identification of the children fully responsive to BH4. Our results therefore suggest the incorporation of BH4 loading test in the management of neonates screened for HPA.     

Screening for coeliac disease in apparently healthy blood donors

As gliadin is a common food antigen for large people, we have developed an ELIS A for the detection of class-specific antigliadin antibodies (AGA), with which sera from a large population of apparently healthy blood donors was analysed. A very high prevalence (1/256) of positive AGA was found. However, the positive predictive value (+PV) was found to be very low, 20% for IgA-AGA and 0% for IgG-AGA alone. When screening large populations with no or few symptoms, it is desirable to have a high +PV to avoid unnecessary biopsies. IgA antiendomyisum antibodies (IgA-EM A) were evaluated both as a single test and in combination with IgA-AGA. When screening individuals for CD in a population with no or few symptoms the easy and cheap IgA-AGA assay should be used as a first test and the IgA-EMA to verify the diagnosis and avoid unnecessary biopsies.     

Serum inhibin B in normal term-born male and female neonates during the first week of life

Inhibin B, a gonadal peptide regulating follicle stimulating hormone (FSH) secretion in adults, has been found during gestation in amniotic fluid, but at birth only in term cord blood of male babies. Since no data are available on the evolution of serum inhibin B during the 1st week of life, we studied changes in inhibin B using a specific and sensitive immunoassay in male and female neonates during the 1st week of life in relation to FSH and to evaluate the possible effect of perinatal factors on inhibin B production. Inhibin B was measured by a specific monoclonal enzyme-linked immunosorbent assay. Inhibin B was detectable in cord blood of all eight longitudinally studied male newborns, correlated negatively with the ponderal index and increased significantly on day 5 (from 54.2 ± 18.5 to 100.4 ± 34.8 ng/l, P < 0.005). Cord blood inhibin B was detected in only 1 out of 13 screened female neonates. In 48 at term-born females in whom inhibin B was measured on the 5th day of life, only 20 cases had a detectable level (between 8 and 68.6 ng/l). Inhibin B concentrations in cord blood and on day 5 were independent of duration of pregnancy, type of delivery, Apgar score and FSH concentration. Conclusion A sexual difference in serum inhibin B is already present at the end of gestation and changes in inhibin B during the 1st week of life are independent of follicle stimulating hormone changes and perinatal factors in both sexes. Our data suggest that neonatal inhibin B could be used to study whether the newborn has functional testes, i.e. in babies with ambiguous genitalia and/or bilateral cryptorchidism. Received: 30 September 1999 and in revised form 23 December 1999 and 20 January 2000 /Accepted: 20 January 2000     

广州市18年新生儿先天性甲低苯丙酮尿症和葡萄糖-6-磷酸脱氢酶缺乏症筛查

目的 探讨广州市新生儿先天性甲低、苯丙酮尿症和葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症筛查方法及其对遗传代谢缺陷病的控制作用.方法 收集广州市新生儿出生3 d时的足跟血滤纸干血斑标本,检测促甲状腺素(TSH)筛查先天性甲状腺功能减低症(CH);检测苯丙氨酸(Phe)检出持续性高苯丙氨酸血症(PHPA),筛查苯丙酮尿症(PKU)和四氢生物蝶呤缺乏症(BH4D);检测红细胞G6PD活性筛查G6PD缺乏症.凡筛查阳性者按疾病诊疗常规进行确诊和治疗,将检出的CH和PHPA作为筛查干预组.将未经过新生儿筛查出现症状才就诊、临床诊断CH和PKU的患儿做为对照组.结果 1989年4月至2007年6月共筛查新生儿945 372名,检出CH 331例,PHPA 29例,G6PD缺乏症39 700例.结果 显示CH发病率为1∶2 856, PHPA为1∶32 599,G6PD缺乏症达1∶23.81.总发病率为4.24%.CH和PHPA共360例,治疗随访357例,治疗率99.2%.PHPA全部免费治疗.平均开始治疗日龄20 d,4～6岁时IQ或0～3岁DQ测定智能正常(IQ或DQ≥90)者320例(89.6%),低于正常(70≤IQ或DQ<90)者36例(10.1%), 智能残疾 (IQ或DQ<70)者1例(0.3%).对照组开始治疗年龄平均3岁,智能残疾26例,筛查组的智能发育明显好于对照组.结论 新生儿代谢病筛查是遗传代谢缺陷病的一种早期诊断和早期防治方法,对检出的CH、PKU进行早期有效治疗,可保持脑和智能发育正常,预防智能性残疾.     

Screening for hip abnormality in the neonate

Clinical screening policies for the detection of hip instability or dysplasia of the hip vary internationally. There is general agreement in the Western world that at birth all hip joints should be clinically assessed by the Ortolani and Barlow tests. Currently, there is no consistency regarding who should undertake the examination, the results being worse when inexperienced personnel are used. These clinical tests have poor sensitivity and should be regarded as surveillance, not screening methods. Since the 1980s ultrasonographic assessment of the hip has become a valuable diagnostic tool. However there is continuing controversy on whether this imaging method should be used universally or selectively for 'at risk' and clinically unstable hip joints. Universal ultrasonographic evaluation may result in over-treatment and selective screening may be no better than the best clinical screening programs in reducing the incidence of 'late' irreducible dislocation of the hip. It is generally accepted that all clinically unstable hips should be imaged by ultrasound by static and dynamic methods in order to confirm the diagnosis and to monitor treatment.     

Familial hypercholesterolaemia with severe cardiac involvement in a boy: successful management and mid-term follow-up

A 13-year-old boy with double heterozygosity for familial hypercholesterolaemia with a 90% left coronary artery main stem stenosis is reported. The patient's cholesterol levels were effectively controlled with weekly sessions of selective low-density lipoprotein cholesterol removal through immunoadsorption by use of an extracorporeal system. Left main coronary artery stenosis was successfully treated with percutaneous transluminal balloon dilation. At 30 months after the intervention and still under treatment with weekly sessions of low-density lipoprotein apheresis the patient is free of cardiac symptoms. He shows normal exercise capacity and normal myocardial perfusion. It is concluded that aggressive management is justified in such patients and may result in a near-normal quality of life.     

Low density lipoprotein in neonates with high cord serum cholesterol levels

Differences in cord serum low density lipoprotein (LDL) composition between male and female neonates with normal or high (≥ 100 mg/dl or ≥ 2.59 mmol/1) serum cholesterol levels were studied in 548 full-term newborn infants of the Toledo Study (Spain), where the absence of known perinatal factors that would alter lipid levels in cord blood was confirmed. The percentage of females with a high serum total cholesterol (TC) level was higher ( p < 0.02) than that of males. ANOVA two-way analysis shows significant interaction of gender and cholesterol level upon LDL-cholesterol, triglycerides and LDL cholesterol/Apoprotein (Apo) B ratio. However, Apo B was higher in those neonates, both male and female, with high cholesterol levels. The LDL fraction carried about 55% of TC in females with high TC levels (HF), whereas it transported just 40% in males with high TC levels (HM). LDL appeared more enriched in cholesterol than in Apo B in HF than in HM ( p < 0.01). An increased level of small LDL particles should be associated with the higher triglyceride level found amongst HM. Results in LDL composition suggest that metabolic gender-related differences in infants with normal or high TC are presented at birth.     

Combining Pulse Oximetry and Clinical Examination in Screening for Congenital Heart Disease

The objective of this study was to evaluate combined pulse oximetry and clinical examination as a screening method for congenital heart disease (CHD) in asymptomatic newborns. Asymptomatic newborns were screened for CHD using pulse oximetry and clinical examination before their discharge from the nursery. Oxygen saturation ≥94% was considered normal. Echocardiography was done for newborns with abnormal readings and for those with significant murmurs. Data concerning undetected cases were collected from the pediatric referral hospital. A total of 5211 cases were screened. Echocardiographic evaluations were done based on low pulse oximetry in five cases and on murmur detection in ten others. The sensitivity of the combined method of screening was 77%, whereas it was 31% for oximetry alone and 46% for clinical examination alone. Specificity was ∼100% for all methods. The positive predictive value of the combined tool was 66.7%. We conclude that combining pulse oximetry and clinical examination can enhance the clinician’s ability to detect life-threatening CHD in a timely manner. This screening method should become a part of the discharge plan for every newborn.     

Thanatophoric dwarfism in Libyan neonates — a report of 3 cases

Three cases of thanatophoric dwarfism are reported from Libya during a period of 16 months showing an incidence of 1:5600 total births. Polyhydramnios was associated with all the three cases and maternal diabetes in one. No known pattern of inheritance was found. One was stillborn and other two died within 30 minutes of birth. The detailed diagnostic features and differential diagnosis is described along with a brief review of literature.     

Analysis of Blood Spot 17α-Hydroxyprogesterone Concentration in Premature Infants—Proposal for Cut-Off Limits in Screening for Congenital Adrenal Hyperplasia—

Blood Spot 17α-hydroxyprogesterone (17-OHP) concentrations in neonates, especially in premature babies, were determined in relation to 1) the gestational age at birth, 2) the equivalent age of gestation at blood sampling and 3) the birth weight. The 17-OHP concentrations were found to be higher with prematurity. Accordingly, the cut-off limit in screening for congenital adrenal hyperplasia (CAH) in premature infants is proposed as 20 ng/ml. Ideal cut-off limits were set by the equivalent age of gestation at blood sampling. Cut-off limits on the basis of gestational age at birth and birth weight are also suggested, where the sampling age is not so advanced. The rate of false positivity in premature infants can be reduced by this method.     

Neonatal screening for biotinidase deficiency in north eastern italy

Biotinidase deficiency satisfies all the criteria for incorporation into neonatal mass screening programmes for inborn errors of metabolism. We report our preliminary experiences with screening of 24300 newborns during a 6 monthperiod when 1 infant with biotinidase deficiency was detected. On the basis of these results, this disorder appears to be as common as other well known metabolic disorders for which mass screening is available.Abbreviation MCD multiple carboxylase deficiency     

Risk factors for invasive fungal infection in neonates

Invasive fungal infection is an uncommon, but increasing cause of morbidity and mortality in neonates. There are few controlled studies defining risk factors for the development of fungal infection in a contemporary neonatal population. This retrospective case-control study was undertaken to investigate antenatal, demographic and postnatal variables that may be potentially important in the development of fungal infection. Two gestation-matched controls were identified for each index case. Information about perinatal and demographic variables, as well as important neonatal outcomes, was obtained from case notes. Microbiological data collected included the presence of fungal colonization, and organisms responsible for invasive fungal infection. Over a 5-y period, 24 infants with invasive fungal infection and 48 controls were identified. Candida albicans was the organism identified in 75% of cases of fungal septicaemia, and in all cases complicated by fungal meningitis. Preceding fungal colonization, pulmonary haemorrhage and intrauterine growth restriction were factors significantly and independently associated with invasive fungal infection. Fifty-four percent of infants with invasive fungal infection died, and 82% of survivors developed chronic lung disease.

Conclusion : Some new and potentially important risk factors for the development of invasive fungal infection in a contemporary population of infants admitted to a neonatal intensive care were identified.