Surfactant protein B deficiency : A rare cause of respiratory failure in a Lebanese newborn

To the Editor: Respiratory diseases secondary to congenital surfactant proteins deficiency are increasingly recognized. To bring to the attention of pediatricians an unusual cause of neonatal respiratory disease, we report on a newborn with progressive respiratory disease due to surfactant protein B (SP-B) deficiency. To our knowledge, this is the first case of SP-B deficiency reported in the Middle East. The patient was a term female newborn delivered vaginally after an uneventful pregnancy to second-degree consanguineous parents. The mother had a stillbirth and a newborn that died on the second day of life of respiratory causes. Four other siblings are normal. Apgar scores were 5 and 8 at 1 and 5 minutes, respectively. The baby was hypotonic and required vigorous stimulation. Birth weight was 3250 grams. Physical examination was remarkable for tachypnea, cyanosis and bilateral decreased air entry. Chest X-ray showed bilateral fine granular infiltrates. The baby was started on antibiotics after a sepsis work up. She required conventional and then high frequency oscillatory ventilation because of hypoxemia and CO2 retention. Echocardiography showed mild right ventricular hypertrophy. On the fourth day of life, she received bovine surfactant (Survanta, Abbott Laboratories, Columbus, Ohio, USA) intratracheally with clinical and radiological improvement that was not sustained on four additional doses. She then received furosemide, hydrocortisone and inhaled nitric oxide with no response. On the seventeenth day of life, she died of persistent hypoxemia with severe respiratory acidosis. Tracheal effluent collected before surfactant administration revealed complete absence of SP-B (Courtesy of Dr. Jeffrey Whitsett, Cincinnati Children’s Hospital). DNA analysis revealed the homozygous 122delT mutation, while both parents were heterozygous for the same mutation (Courtesy of Dr. Lawrence Nogee, Johns Hopkins University). SP-B is a hydrophobic protein involved in the adsorption of surfactant phospholipids to the air-liquid interface. It is coded by a gene of 11 exons on chromosome 2. In 1993, Nogee et al reported SP-B deficiency causing severe respiratory disease, as described in our patient.1 The patient and a sibling who had died earlier had a frame-shift mutation caused by a 2 base-pair insertion (121ins2) in exon 4 of the SP-B gene.2 Radiologically, SP-B deficiency presents like hyaline membrane disease. Histopathologically, the distal airspaces appear filled with lipid-rich, periodic acid Schiff-positive, eosinophilic proteinaceous material.1 The diagnosis is established by failing to identify SP-B in the tracheal effluent and is confirmed by genetic studies, which show a mutation on the SP-B gene. More than 13 mutations have been described,3 of which (121ins2) accounts for about 70%. Its frequency in the United States is estimated to be 1 per 1000–3000 individuals.4 The 1043ins3 mutation was detected in 2 unrelated Pakistani families.3 The mutation described in the present report (122delT) was described in a consanguineous kindred of Kurdish descent,5 and in three unrelated Lebanese families (L. Nogee, personal communication). The recognition of specific mutations in various ethnic groups may allow diagnosis in individual patients and population-wide studies for the determination of gene frequency. This would gain particular importance in our population, where consanguinity is prevalent. SP-B deficiency is usually fatal, unless treated with lung transplantation.6 Gene transfer therapy may be the treatment modality of the future.