Fumarase Deficiency: A Case With a New Pathogenic Mutation and a Review of the Literature.

Fumarase deficiency (FD) is a rare and severe autosomal disorder, caused by inactivity of the enzyme fumarase, due to biallelic mutations of the fumarase hydratase (FH) gene. Several pathogenic mutations have been published. The article describes an infant with failure to thrive, microcephaly, axial hypotonia, and developmental retardation with increased excretion of fumarate, no activity of fumarase and a homozygous mutation of the FH gene, which was until recently only known as a variant of unknown significance. Carriers of pathogenic mutations in the FH gene are at risk for developing renal cell carcinoma and should therefore be screened. Both parents were healthy carriers of the mutation and had decreased levels of enzyme activity. In addition, the article presents an overview and analysis of all cases of FD reported thus far in the literature.

[A neonate with soft tissue protruding through the umbilicus]. / Een neonaat met weefsel uit de navel.

A 6-week-old neonate presented with soft tissue protruding through the umbilicus due to a persisting ductus omphalo-entericus. This remnant was surgically removed the next day.

Congenital diaphragmatic hernia: long-term risk of gastroesophageal reflux disease.

OBJECTIVES: Gastroesophageal reflux disease (GERD) is a well-recognized consequence of congenital diaphragmatic hernia (CDH). Results of studies examining predictive factors for early and late GERD are inconclusive. The aim of this study was to assess the incidence of early (<2 years) and late GERD (≥6 years) following CDH repair and to identify predictive variables. PATIENTS AND METHODS: Of 183 patients born with high-risk CDH, 107 survived and 38 were excluded. Perinatal and postnatal data of 69 eligible patients were analysed to identify variables predictive for early GERD. For the follow-up study, 58 patients (84%) (ages 12.1 ± 3.4 years; range 6-17) completed a standardised questionnaire. Results were compared with those from a healthy control group (n = 83). Patients who had a score indicating increased risk of GERD underwent further diagnostic assessment. Predictive factors for early and late GERD were identified using multivariate regression analysis. RESULTS: Early GERD was demonstrated in 27 patients (39%). Patch closure and intrathoracic position of the stomach were independent predictive variables for early GERD. At the time of follow-up, 9 of 58 patients (16%) had symptoms suggestive of GERD. In 7 patients (12%), late GERD was confirmed. For late GERD, however, no perinatal or postnatal risk factors were identified. CONCLUSIONS: Early GERD is more common in CDH patients with patch closure or intrathoracic position of the stomach. Predictive factors for late GERD could not be identified and screening for early GERD does not protect for future GERD; therefore, long-term follow-up for GERD in CDH survivors is mandatory.

Pulmonary function and exercise testing in adult survivors of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is accompanied by pulmonary hypoplasia and structural abnormalities of the pulmonary vascular bed. It is unknown whether pulmonary function, exercise capacity, and gas exchange during exercise are impaired in adult CDH survivors. The objective of this study was to assess the long-term pulmonary function, exercise capacity, and gas exchange during exercise and relate these findings with quality of life. Of the 23 patients eligible for this study, 12 adult CDH survivors (mean age, 24.3 +/- 4.1 years) with high-risk CDH agreed to participate. Pulmonary function tests, diffusion capacity, and a cardiopulmonary exercise test (CPET) were performed. The FEV1 (mean z-score +/- SD; -1.30 +/- 1.37), FEF25-75% (-1.49 +/- 1.14), and the KCO (-1.03 +/- 1.24) were found to be lower in CDH survivors. The RV/TLC ratio (28.2% +/- 5.0%) was found to be higher. Despite these abnormalities, percent predicted work load (102% +/- 17.2%) and percent predicted maximal oxygen uptake (90.8% +/- 18.9%) were normal in most of the patients. The quality of life of CDH survivors, assessed with the SF-36 questionnaire, is comparable to the general population. Comparison of participants to non-participants did not reveal significant differences in clinical characteristics. In this first study assessing pulmonary function in adult survivors of CDH, mild airway obstruction was observed in most of the patients together with a slightly reduced diffusion capacity for CO. Exercise capacity and gas exchange parameters were normal in this group, indicating that patients do not have a physical impairment, as reflected by a normal quality of life of CDH patients.