Efficacy of multidisciplinary approach in the treatment of two cases of nonclassical infantile glycogenosis type II.

Glycogenosis type II (GSD II) is a lysosomal storage disorder due to acid alpha-glucosidase deficiency. We report the results of a clinical multidisciplinary approach in two cases of nonclassical infantile GSD II. The patients received a high-protein diet by percutaneous enteral gastrostomy (PEG), mechanical ventilatory support by tracheostomy and a physiotherapy programme. After 12 months of treatment, the patients showed significant improvement in muscular strength, nutritional state and respiratory function. Electrocardiography (ECG) and echocardiography improved in both patients. They maintained good clinical conditions for a period of 18 and 20 months, respectively; thereafter they presented with an elevated and persistent fever that was not correlated to a septic status and was not responsive to any antipyretic treatment. They deteriorated progressively and died. This study shows how a multidisciplinary approach may be useful to improve, even if temporarily, the clinical course of nonclassical infantile GSD II.

Prenatal echocardiographic appearance of arrhythmogenic right ventricle dysplasia: a case report.

We report a case of arrhythmogenic right ventricular dysplasia (ARVD) diagnosed prenatally by echocardiography at 24 weeks gestation. The 4-chamber view showed a large outpouched area extending from below the tricuspid valve to the insertion of the moderator band; the affected wall appeared thin and akinetic, with absence of flow at color Doppler investigation and no evidence of cardiovascular failure. The size of the outpouched area was unchanged at subsequent controls (25 and 26 weeks gestation) when frequent extrasystoles occurred, probably of a ventricular origin. The pregnancy was terminated at 27 weeks. The histopathologic examination of the fetal heart showed the presence of clusters of adipocytes interspersed with myocardial fibers, consistent with the diagnosis of ARVD.

Intractable fever and cortical neuronal glycogen storage in glycogenosis type 2.

Glycogenosis type 2 is an autosomal recessive glycogen storage disorder caused by deficiency of lysosomal acid alpha-glucosidase. Different phenotypes are recognized. The authors describe two children affected by the late infantile form; both presented terminal hyperthermia not caused by infections. Autopsy performed in one case showed diffuse glycogen storage in the CNS neurons. In light of current interest in enzyme replacement therapy, this finding casts some doubt on how effective enzyme replacement therapy will be unless it can be targeted directly into the CNS.

Early screening for fetal cardiac anomalies by transvaginal echocardiography in an unselected population: the role of operator experience.

OBJECTIVES: To examine the accuracy of early transvaginal fetal echocardiography performed in an unselected population by operators with different levels of experience and to compare the results with those obtained from a referral population. DESIGN: Prospective study. METHODS: A series of 4785 unselected fetuses and 221 referred fetuses were screened at 13-15 weeks' gestational age by transvaginal echocardiography. For each fetus, visualization of the four-chamber view plus the origin of the great arteries was attempted. Color Doppler imaging was only performed in cases of cardiac malformations already identified by two-dimensional echocardiography. The scans were performed by seven operators with different levels of experience. Reliability was assessed by conventional transabdominal echocardiography at 20-22 weeks, by postnatal follow-up in the first 3 months of life, and/or by autopsy in all cases of termination or fetal death. RESULTS: The rate of complete visualization (four-chamber view plus great arteries) was 47.5% in the unselected population, and 76.9% in the referral population. There were four (0.08%) true positives among the unselected fetuses, and five (2.3%) among referrals, mostly with enlarged nuchal translucency or other malformations. Among the unselected fetuses, nine false negatives were detected by transabdominal echocardiography. Improvement in the operators' ability to recognize cardiac anomalies in unselected population was disappointing and was influenced more by individual approach than by the number of examinations performed. CONCLUSIONS: Early screening for cardiac anomalies among unselected fetuses is ill-advisable. The usefulness of an early approach is confirmed in high risk fetuses or in the presence of enlarged nuchal translucency when performed by expert operators.

Idiopathic arterial calcification of infancy: effectiveness of prostaglandin infusion for treatment of secondary hypertension refractory to conventional therapy: case report.

A premature baby had severe hypertension associated with idiopathic arterial calcification of infancy. Despite the fact that there was laboratory evidence of renin-mediated hypertension, the disease was refractory to specific renin antagonist and failed to respond to conventional medical treatment. Prostaglandin E1 (PGE1) infusion (dosage range 0.017-0.068 microgram/kg/min) promptly controlled hypertension on two occasions. The drug was given for a total of 65 days and then stopped after the appearance of severe thrombocytopenia; other side effects included sporadic hyperthermia and irritability. Blood pressure was then stabilized satisfactory by a multiple-antihypertensive regimen. In the light of these findings, we believe that PGE1 infusion is a possible therapeutic alternative for babies with idiopathic arterial calcification complicated by severe hypertension refractory to conventional treatment.

Conotruncal anomalies in prenatal life.

This retrospective multicenter study represents an analysis of the intrauterine determinants of the prognosis for conotruncal anomalies. Data regarding reason for referral, presence of chromosomal or extracardiac anomalies, pregnancy and surgical outcome were recorded in 67 cases of conotruncal anomalies from three Italian referral units. Chromosomal aberrations effected 11 of the 60 (18.3%) fetuses in which a karyotype was available. Extra-cardiac malformations were present in 25/67 cases (37.3%). No chromosomal anomalies were present in fetuses with complete or corrected transposition of the great arteries. However, tetralogy of Fallot and double-outlet right ventricle were associated with chromosomal anomalies in 22% and 38% of cases, respectively, and with extracardiac anomalies in 45% and 46% of cases, respectively. Only 20 of the 67 (31%) cardiac malformations were associated with an abnormal four-chamber view. There were 28 (41.7%) terminations of pregnancy, six (8.9%) intrauterine deaths and 16 (23.8%) neonatal deaths. Seventeen neonates (25.3%) are currently alive, and 15 of these have undergone reparative surgery. The prognosis of conotruncal anomalies is poorer when the conditions is diagnosed in utero. This is mainly due to the frequent association with chromosomal and/or extracardiac anomalies, often leading to intrauterine or early neonatal death.

Fetal heart screening in low-risk pregnancies.

The aim of this study was to assess whether a screening program for fetal cardiac malformations is justified in a low-risk population, and which factors influence its accuracy. The fetal heart was evaluated in 7024 pregnant women at 20-22 weeks, and evaluation was repeated at a more advanced gestational age in 9% of cases. Cardiological follow-up was continued postnatally until 2 years of age. The overall prevalence of cardiac anomaly was 0.93%. The incidences of major and minor defects were 0.44% and 0.48%, respectively. There were 23 true positives (0.33%): in 20 cases, the diagnosis was made in the second trimester, and 13 women (65%) chose termination of pregnancy. Seventeen of the 20 cases identified in the second trimester were serious malformations. There were 42 false negatives (0.60%). Of these, 12 had signs of cardiac dysfunction at birth or within the 1st month of life, and three of them died as a result of their cardiac anomaly. There were eight false positives (0.11%), all of a minor type. Six abnormal karyotypes, out of a total of 21 performed in the true-positive group (28.5%), were found. In addition, five of the 42 newborns in the false-negative group had trisomy 21. The overall sensitivity was 35.4%, and 61.3% for major defects. The accuracy in two distinct periods was estimated because the level of experience of the operators was different: sensitivity was 45.2% in period 1 (1986-88) (77.8% for major defects) and 26.5% in period 2 (1989-92) (52.9% for major defects). We conclude that a fetal heart screening program in the obstetric population is justified. It defines a high-risk group for karyotyping, allows planning of delivery in a tertiary center or the choice of terminating the pregnancy for the parents and appears to have a positive cost-benefit ratio. A crucial factor is the level of training and experience of the operators, who need specific teaching support.

Early fetal endocardial fibroelastosis and critical aortic stenosis: a case report.

Endocardial fibroelastosis is characterized by an abnormal thickening of the endocardium of one or both ventricles; the disorder may occur with or without other cardiac anomalies. A diagnosis of endocardial fibroelastosis in utero using fetal echocardiography may be made on the basis of increased echodensity of the endocardium and poor contractility of the ventricle. We describe a case of very early diagnosis of fibroelastosis and aortic valve stenosis observed in utero at 14 weeks' gestation by transvaginal echocardiography.

[Efficacy of magnesium in a case of neonatal pulmonary hypertension refractory to the usual therapies]. / Efficacia del magnesio in un caso di ipertensione polmonare neonatale resistente alle comuni terapie.

We describe a premature baby with X pentasomy, having a severe pulmonary hypertension secondary to perinatal asphyxia and hyaline membrane disease which appeared to be refractory to conventional treatments (hyperventilation, tolazoline, prostacyclin). Oxygenation and pulmonary hypertension rapidly improved after starting magnesium sulphate infusion (loading dose: 20 mg/kg e.v. of elementary Mg, followed by continuous infusion of 2-4 mg/kg/hr during 6 days). The therapy was associated with hypermagnesemia (5-7 mg/100 ml) and transitory side effects (hypocalcemia, muscular and bladder paresis, bradycardia without hemodynamic decompensation). We suggest that magnesium therapy might be considered in newborns with severe and persistent pulmonary hypertension.

Fetal echocardiography: the role of the screening procedure.

1841 pregnant women without any risk factor for heart malformation of the fetus underwent an echocardiographic screening at an average gestational age of 23 weeks. Seven cases of heart diseases were diagnosed (0.38%), of which one died in utero at 28 weeks and another one was interrupted. In four cases the karyotype was carried out prenatally, while in the remaining three it was performed only after birth. There were 11 false-negative (0.59%), mainly concerning anomalies of minor clinical significance. Within this group, two newborns with interatrial defect of the ostium secundum type appeared to be affected by trisomy 21. Therefore, the rate of congenital heart diseases in live births not at risk (0.86%) was in line with the data reported in paediatric literature. On the other hand, the association with chromosomal anomalies was surprisingly frequent (4 out of the 9 karyotypes performed were anomalous). Such finding should be verified by studying a larger non-selected population. However, a fetal karyotype should be offered, for its practical consequences, also in those cases of cardiac anomalies of lesser clinical significance.

[Natural history of patients with isolated atrial fibrillation]. / La storia naturale dei pazienti con fibrillazione atriale isolata.

Sixty three patients (pts) (aged less than or equal to 50 years) with a history of "lone" atrial fibrillation (AF) and normal heart size at radiological examination were followed-up for a mean period of 95 months (range 1-360). The arrhythmia remained paroxysmal in 43 pts, became chronic in 13, while in 7 could not be reverted to sinus rhythm at the time of first observation. Clinical examination was normal in 58 pts; in 23 echocardiography disclosed mild abnormalities. In 2 pts auscultation revealed a mid-systolic apical click, i n one a mid-systolic murmur and in 2 click and murmur together. These findings were correlated to slightly pathological echocardiographic patterns. M-mode and B-mode echocardiography yielded normal results in 35 pts and showed minor pathological findings in 28 (16 with paroxysmal AF and 12 with chronic AF). Thyroid hormones, tested in 58 pts, were within normal limits in 53, showed decreased T4 in 2 and increased T3 in 3 (2 of whom in treatment with amiodarone). During the follow-up period, no patient had a deterioration of the clinical status from the cardiovascular point of view. However, one patient suffered an episode of cerebral embolism, with rapid resolution, and one a cerebral transient ischemic attack. In conclusion "lone" AF has a favourable prognosis and systemic anticoagulation is not indicated, particularly in the absence of left atrial dilatation.

Use of oral verapamil in long-term treatment of neonatal, paroxysmal supraventricular tachycardia. A pharmacokinetic study.

Efficacy and pharmacokinetics of verapamil were studied in two neonates affected by supraventricular paroxysmal tachycardia, under maintenance treatment with the drug. Verapamil proved to be fully effective in suppressing arrhythmic episodes at the daily doses of 1.5 mg/kg four times a day in case 1 and of 2 mg/kg in case 2. The results of plasma half-life of the drug, calculated in a dose interval, were 3.14 hr and 2.10 hr, respectively. In patient 2, doses less than 0.95 mg/kg four times a day did not produce detectable drug plasma levels, while a further stepwise increase of dose up to 2 mg/kg four times a day produced a steep rise in trough concentration. So, in view of this dose-concentration relationship, caution is recommended in adjusting verapamil oral dosage.