VACTERL Association: A New Case with Biotinidase Deficiency and Annular Pancreas

Abstract

VACTERL (V – Vertebral anomalies, A – Anal atresia, C – Cardiovascular anomalies, T – Tracheoesophageal fistula, E – Esophageal atresia, R – Renal (Kidney) and/or radial anomalies, L – Limb defects) association includes vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal dysplasia, and limb anomalies. Less frequent defects seen with VACTERL association are prenatal and postnatal growth deficiency, laryngeal stenosis, ear anomaly, large fontanels, defect of lower limb, rib anomaly, tethered cord, and defects of external genitalia. We report a case of VACTERL association who had concomitant biotinidase deficiency and annular pancreas, which has not been previously reported.

• hydroureteronephrosis
• VACTERL association
• tracheoesophageal fistula
• anal atresia
• biotinidase deficiency
• esophageal atresia

CASE REPORT

The patient was born at 35 weeks of gestation with birth weight of 2300 g. He was the first child of nonconsanguineous parents. The pregnancy was complicated with polyhydramnios, gestational diabetes, and hypothyroidism diagnosed during pregnancy. Triangular face, low-set ears, right choanal atresia, heart murmur, bilateral palpable kidneys, anal atresia with anal dimple, and right inguinal hernia were detected in the neonatal period.

He had had surgical corrections for his imperforate anus within 24 h of life and for esophageal atresia at 3rd day of life, combined with tracheoesophageal fistula ligation. Thal fundoplication with gastrostomy opening was applied at 17th day. He had continuous vomiting and feeding intolerance because of brid ileus at 24th day of life.

He had esophageal atresia, anal atresia, tracheoesophageal fistula, atrial septal defect, hydro-ureteronephrosis, and annular pancreas accompanied with biotinidase deficiency.

He was on mechanical ventilation for 6 months with multiple unsuccessful attempts for extubation. Despite surgical treatment of the congenital malformations, oral biotin for biotinidase deficiency, and intense supportive care, the patient unfortunately passed away at 6 months with sepsis and respiratory insufficiency (Figure 1).

Figure 1. Patient at 6 months of age, with respiratory failure, in intensive care unit.

Antenatal ultrasound scan had confirmed bilateral hydroureteronephrosis and esophageal atresia. Postnatal follow-up ultrasonography at 1 week showed right kidney 49.2 mm, parenchyma 3.8 mm with grade 3 calyceal ectasia, and the left kidney was 44.5 mm, parenchyma 4.7 mm with the proximal ureter 9 mm and annular pancreas.

The radiographic evaluation revealed nasogastric coiling, double-bubble sign, and vertebral defects (Figure 2). Echocardiography demonstrated an atrial septal defect and dilatation of both the right atrium and ventricle. Biotinidase enzyme level was 7% (profound deficiency: <10% enzyme level) detected by newborn screening. Metabolic screen tests were otherwise normal.

Figure 2. Anterioposterior chest and abdomen radiograph shows the vertebral deformities and colostomy.

Chromosomal analysis was normal male: 46, XY.

Complete blood count, coagulation profile, and biochemical tests were normal except for persistent hypoglycemia, direct hyperbilirubinemia, and high liver function tests. Leukocyte count and C-reactive protein values oscillated according to clinical deteriorations.

Candida glabrata was isolated in blood culture.

DISCUSSION

Patients with VACTERL (V – Vertebral anomalies, A – Anal atresia, C – Cardiovascular anomalies, T – Tracheoesophageal fistula, E – Esophageal atresia, R – Renal (Kidney) and/or radial anomalies, L – Limb defects) association frequently (70%) show non-VACTERL-type features such as single umbilical artery, genital defects, and respiratory tract anomalies.¹ Pancreatic hypoplasia is described with VATER association.^2,3 Gross malformations of gastrointestinal tract such as esophageal atresia, tracheoesophageal fistula, annular pancreas, midgut malrotation, and duodenal and anal atresia resulted from mutations of hedgehog signaling molecules in animal studies but not yet shown in humans.⁴ Defective hedgehog signaling can play a possible causative role in concomitant occurrence of annular pancreas and the other features of VACTERL association seen in our case.⁴

To our knowledge, the occurrence of annular pancreas and biotinidase deficiency with VACTERL association is not reported before.

ACKNOWLEDGMENT

Funding. No financial assistance for support of this study was received.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.