Neonatal and Pediatric Medicine
Open Access

We report neonate with Surfactant metabolism dysfunction type 3, with critical acute respiratory distress syndrome, accompanied by respiratory failure in Riyadh, KSA. A 25-year-old gravid a two, Para one woman at 40 weeks gestation, with regular antenatal care, and normal prenatal screening, without chronic illness. The female infant is vigorous, and Apgar scores were 8 and 9 at 1 and 5 minutes of life respectively, baby transfer to nursery section in good condition with a birth weight of 3000 g. First degree relative consanguineous parents, they had first sibling born at 27 weeks gestation, who was Neonatal Intensive Care Unit(NICU) graduate, no family history of similar condition. At the age of two hours, the infant shifted to (NICU) secondary to respiratory distress. Respiratory rate was 70 per minute, oxygen saturation 86% on Bubble CPAP, temperature 36.5, tachypneic, chest recession and bilateral diminished air entry. No dimorphic features, heart sounds are audible in all auscultator areas, loud second heart sound is detected in pulmonary component, plus soft murmur, unremarkable neurological and abdominal examination. On admission, the infant connected to non-invasive ventilator support for 58 hours, then intubated and connected to mechanical ventilator due to desaturation beside increase oxygen requirement. During intubation, a fresh blood noticed in ET tube. Radiograph shows granular, hazy, ground-glass interstitial pacifications, Initial therapeutic dose of surfactant was given and followed by multi doses, which gave a little pit of improvement that allowed to keep patient out of invasive mechanical ventilator for 5 days. The infant has been kept between conventional and high frequency ventilators and death was announced by day 43 of life.

Investigations

➢ Initial laboratory evaluation included a white blood cell count of 17.98 (× 10 3/μL), with 21% neutrophils, 40% lymphocytes, 8% monocytes, hemoglobin 21(g/dl), platelets 241, and CRP 21.98 (Tables 1 and 2) showed patient criterion, laboratory values and work up during hospital course (Figures 1-3).

Table 1: Work up during hospital course.

Table 2: patient criteria, laboratory values and work up.

Figure 1: X-rays on admission, showed bilateral hazy, glandular pictures.

Figure 2: X-ray at day 3, showed increased, haziness, granularity and ground glass interstitial opacification.

Figure 3: X-ray, at day 7, more ground glass interstitial opacification.

➢ Genetic study: blood sample sent to Germany, cent gene labs showed: A homozygous pathogenic variant was identified in the ABCA3 gene (Figures 4 and 5). The diagnosis of autosomal recessive surfactant metabolism dysfunction type 3 is confirmed.

Figure 4: X-ray, at day 15, dose not shows improvement, increased glandular pattern.

Figure 5: X-ray, at day 30, revealed severe ground glass interstitial opacification, almost white out lungs.

The genetic disorders of surfactant metabolism dysfunction are caused by mutations in genes encoding proteins which essential for both function and creation of pulmonary surfactant. It’s rare disorders that may cause sporadic or familial lung disease, with clinical presentations ranging from neonatal respiratory failure to childhood or adult-onset interstitial lung disease. Beside the major surfactant proteins, additional proteins including ABCA3 (member A3 of the ATP binding cassette family of proteins), the TTF-1 (Thyroid Transcription Factor 1) are also important to produce functioning surfactant [1,2].

Surfactant Metabolism Dysfunction-3(SMDP3) is caused by homozygous or compound heterozygous mutation in the ABCA3 gene and appears to be the most common cause of genetic surfactant dysfunction in humans [3-5]. Mutations which related to loss or functional defect of ABCA3 protein are inherited in an autosomal recessive pattern [MIM #610921]. Two types of mutation are known, (Type1 mutation), which related to absent, decreased protein expression, or abnormal trafficking, while (Type 2 mutation) associated with diminished functional activity of ABCA3 protein [6,7]. As supported by animal and human studies, severe neonatal form of the disease is thought to be result from functional surfactant defect [8,9]. In humans with ABCA3 mutations, lack amounts of mature SP-C and altered processing of pro SP-B to SP-B have been observed [10].

ABCA3 mutations vary in its presentation and severity, according to the part on the genotype, as shown in a series of 185 individuals with various ABCA3 mutations. It is found that the most severe phenotype with (respiratory failure at birth, leading to death or lung transplantation by one year of age) was found in 100 percent of those with mutations predicted to preclude ABCA3 expression on both alleles, as compared with 75 percent of those with genotypes of either null/other or mutations [11].

The carrier frequency in the population with ABCA3 mutation has been estimated to be between 1 in 33 to 1 in 70 individuals, which predicting a disease incidence of between 1 in ~4400 to 1 in~20,000 [12].

Surfactant dysfunction due to mutations in ABCA3 has a more variable phenotype, depending in part on the genotype. The initial presentation with a severe RDS-picture in a full-term neonate. The resultant disease is progressive may leads to early death in some infants, while other infants may stabilize or improve. Patients with ABCA3 mutations may also present later in infancy or childhood. Cough, tachypnea, hypoxemia, gastro esophageal reflux, and failure to thrive are frequent features [13].

Full term babies with progressive respiratory distress, not responding to exogenous surfactant and ventilation support and highly consanguinity, increase vigilance and a high index of suspicion of congenital surfactant deficiency.

We recommended parenteral carrier testing to confirm homozygosis of the variant in place of compound heterogeneity for large deletion.

We are indebted to NICU team, colleagues, involved subspecialty departments (Pulmonology, Cardiology, Radiology) and nursing staff, for their unlimited helpful.