Surfactant Protein B Deficiency Caused by Homozygous C248X Mutation—A Case Report and Review of the Literature

Abstract

Objective Surfactant protein B (SP-B) deficiency is a rare autosomal recessive disorder that is usually rapidly fatal. The c.397delCinsGAA mutation (121ins2) in exon 4 is found in more than two-thirds of patients.

Design We report on a fatal case of SP-B deficiency caused by a homozygous C248X mutation in exon 7 of the SP-B gene. In addition, we provide an update of the current literature. The EMBASE, MEDLINE, and CINAHL databases were systematically searched to identify all papers published in the English and German literature on SP-B deficiency between 1989 and 2013.

Results SP-B deficiency is characterized by progressive hypoxemic respiratory failure generally in full-term infants. They present with symptoms of respiratory distress and hypoxemia; chest X-ray resembles hyaline membrane disease. Prenatal diagnosis is possible from amniotic fluid or chorionic villi sampling.

Conclusion Thirty-four mutations have been published in the literature. Treatment options are scarce. Gene therapy is hoped to be an option in the future.

Keywords

surfactant - newborn infant - respiratory distress - surfactant protein B deficiency

• References

• 1 Cole FS, Hamvas A, Rubinstein P , et al. Population-based estimates of surfactant protein B deficiency. Pediatrics 2000; 105 (3, Pt 1): 538-541
• 2 Hamvas A, Trusgnich M, Brice H , et al. Population-based screening for rare mutations: high-throughput DNA extraction and molecular amplification from Guthrie cards. Pediatr Res 2001; 50 (5) 666-668
• 3 Tredano M, Griese M, de Blic J , et al. Analysis of 40 sporadic or familial neonatal and pediatric cases with severe unexplained respiratory distress: relationship to SFTPB. Am J Med Genet A 2003; 119A (3) 324-339
• 4 Nogee LM. Alterations in SP-B and SP-C expression in neonatal lung disease. Annu Rev Physiol 2004; 66: 601-623 [Review]
• 5 Nogee LM, Wert SE, Proffit SA, Hull WM, Whitsett JA. Allelic heterogeneity in hereditary surfactant protein B (SP-B) deficiency. Am J Respir Crit Care Med 2000; 161 (3, Pt 1) 973-981
• 6 Herman TE, Nogee LM, McAlister WH, Dehner LP. Surfactant protein B deficiency: radiographic manifestations. Pediatr Radiol 1993; 23 (5) 373-375
• 7 Nogee LM, de Mello DE, Dehner LP, Colten HR. Brief report: deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis. N Engl J Med 1993; 328 (6) 406-410
• 8 Hamvas A, Cole FS, deMello DE , et al. Surfactant protein B deficiency: antenatal diagnosis and prospective treatment with surfactant replacement. J Pediatr 1994; 125 (3) 356-361
• 9 Hamvas A, Nogee LM, Mallory Jr GB , et al. Lung transplantation for treatment of infants with surfactant protein B deficiency. J Pediatr 1997; 130 (2) 231-239
• 10 Wert SE, Whitsett JA, Nogee LM. Genetic disorders of surfactant dysfunction. Pediatr Dev Pathol 2009; 12 (4) 253-274 [Review]
• 11 Weaver TE, Whitsett JA. Function and regulation of expression of pulmonary surfactant-associated proteins. Biochem J 1991; 273 (Pt 2): 249-264
• 12 Pilot-Matias TJ, Kister SE, Fox JL, Kropp K, Glasser SW, Whitsett JA. Structure and organization of the gene encoding human pulmonary surfactant proteolipid SP-B. DNA 1989; 8 (2) 75-86
• 13 deMello DE, Nogee LM, Heyman S , et al. Molecular and phenotypic variability in the congenital alveolar proteinosis syndrome associated with inherited surfactant protein B deficiency. J Pediatr 1994; 125 (1) 43-50
• 14 Nogee LM, Garnier G, Dietz HC , et al. A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds. J Clin Invest 1994; 93 (4) 1860-1863
• 15 Voorhout WF, Veenendaal T, Haagsman HP , et al. Intracellular processing of pulmonary surfactant protein B in an endosomal/lysosomal compartment. Am J Physiol 1992; 263 (4, Pt 1): L479-L486
• 16 Andreeva AV, Kutuzov MA, Voyno-Yasenetskaya TA. Regulation of surfactant secretion in alveolar type II cells. Am J Physiol Lung Cell Mol Physiol 2007; 293 (2) L259-L271 [Review]
• 17 Ryan US, Ryan JW, Smith DS. Alveolar type II cells: studies on the mode of release of lamellar bodies. Tissue Cell 1975; 7 (3) 587-599
• 18 Pérez-Gil J. Structure of pulmonary surfactant membranes and films: the role of proteins and lipid-protein interactions. Biochim Biophys Acta 2008; 1778 (7-8) 1676-1695
• 19 Serrano AG, Pérez-Gil J. Protein-lipid interactions and surface activity in the pulmonary surfactant system. Chem Phys Lipids 2006; 141 (1-2) 105-118
• 20 Yamano G, Funahashi H, Kawanami O , et al. ABCA3 is a lamellar body membrane protein in human lung alveolar type II cells. FEBS Lett 2001; 508 (2) 221-225
• 21 Weaver TE, Conkright JJ. Function of surfactant proteins B and C. Annu Rev Physiol 2001; 63: 555-578 [Review]
• 22 Ridsdale R, Post M. Surfactant lipid synthesis and lamellar body formation in glycogen-laden type II cells. Am J Physiol Lung Cell Mol Physiol 2004; 287 (4) L743-L751
• 23 Yusen RD, Cohen AH, Hamvas A. Normal lung function in subjects heterozygous for surfactant protein-B deficiency. Am J Respir Crit Care Med 1999; 159 (2) 411-414
• 24 Stenson PD, Ball EV, Mort M , et al. Human Gene Mutation Database (HGMD): 2003 update. Hum Mutat 2003; 21 (6) 577-581
• 25 Ballard PL, Nogee LM, Beers MF , et al. Partial deficiency of surfactant protein B in an infant with chronic lung disease. Pediatrics 1995; 96 (6) 1046-1052
• 26 Dunbar III AE, Wert SE, Ikegami M , et al. Prolonged survival in hereditary surfactant protein B (SP-B) deficiency associated with a novel splicing mutation. Pediatr Res 2000; 48 (3) 275-282
• 27 Floros J, Veletza SV, Kotikalapudi P , et al. Dinucleotide repeats in the human surfactant protein-B gene and respiratory-distress syndrome. Biochem J 1995; 305 (Pt 2) 583-590
• 28 Klein JM, Thompson MW, Snyder JM , et al. Transient surfactant protein B deficiency in a term infant with severe respiratory failure. J Pediatr 1998; 132 (2) 244-248
• 29 Lin Z, deMello DE, Wallot M, Floros J. An SP-B gene mutation responsible for SP-B deficiency in fatal congenital alveolar proteinosis: evidence for a mutation hotspot in exon 4. Mol Genet Metab 1998; 64 (1) 25-35
• 30 Schuerman FA, Griese M, Gille JP, Brasch F, Noorduyn LA, van Kaam AH. Surfactant protein B deficiency caused by a novel mutation involving multiple exons of the SP-B gene. Eur J Med Res 2008; 13 (6) 281-286
• 31 Somaschini M, Wert S, Mangili G, Colombo A, Nogee L. Hereditary surfactant protein B deficiency resulting from a novel mutation. Intensive Care Med 2000; 26 (1) 97-100
• 32 Tredano M, Cooper DN, Stuhrmann M , et al. Origin of the prevalent SFTPB indel g.1549C > GAA (121ins2) mutation causing surfactant protein B (SP-B) deficiency. Am J Med Genet A 2006; 140 (1) 62-69
• 33 Tredano M, van Elburg RM, Kaspers AG , et al. Compound SFTPB 1549C—>GAA (121ins2) and 457delC heterozygosity in severe congenital lung disease and surfactant protein B (SP-B) deficiency. Hum Mutat 1999; 14 (6) 502-509
• 34 Wegner DJ, Hertzberg T, Heins HB , et al. A major deletion in the surfactant protein-B gene causing lethal respiratory distress. Acta Paediatr 2007; 96 (4) 516-520
• 35 Williams GD, Christodoulou J, Stack J , et al. Surfactant protein B deficiency: clinical, histological and molecular evaluation. J Paediatr Child Health 1999; 35 (2) 214-220
• 36 Beers MF, Hamvas A, Moxley MA , et al. Pulmonary surfactant metabolism in infants lacking surfactant protein B. Am J Respir Cell Mol Biol 2000; 22 (3) 380-391
• 37 Dirksen U, Nishinakamura R, Groneck P , et al. Human pulmonary alveolar proteinosis associated with a defect in GM-CSF/IL-3/IL-5 receptor common beta chain expression. J Clin Invest 1997; 100 (9) 2211-2217
• 38 Martinez-Moczygemba M, Doan ML, Elidemir O , et al. Pulmonary alveolar proteinosis caused by deletion of the GM-CSFRalpha gene in the X chromosome pseudoautosomal region 1. J Exp Med 2008; 205 (12) 2711-2716
• 39 Suzuki T, Sakagami T, Rubin BK , et al. Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA. J Exp Med 2008; 205 (12) 2703-2710
• 40 Clark JC, Wert SE, Bachurski CJ , et al. Targeted disruption of the surfactant protein B gene disrupts surfactant homeostasis, causing respiratory failure in newborn mice. Proc Natl Acad Sci U S A 1995; 92 (17) 7794-7798
• 41 Andersen C, Ramsay JA, Nogee LM , et al. Recurrent familial neonatal deaths: hereditary surfactant protein B deficiency. Am J Perinatol 2000; 17 (4) 219-224
• 42 Ball R, Chetcuti PA, Beverley D. Fatal familial surfactant protein B deficiency. Arch Dis Child Fetal Neonatal Ed 1995; 73 (1) F53
• 43 Ferzli G, Yunis KA, Mroueh S. Surfactant protein B deficiency: a rare cause of respiratory failure in a Lebanese newborn. Ann Saudi Med 2006; 26 (1) 69-70
• 44 Grasemann H, de Perrot M, Bendiak GN , et al. ABO-incompatible lung transplantation in an infant. Am J Transplant 2012; 12 (3) 779-781
• 45 Herting E, Schiffmann H, Roth C, Johansson J. Surfactant lavage demonstrates protein fibrils in a neonate with congenital surfactant protein b deficiency. Am J Respir Crit Care Med 2002; 166 (9) 1292-1294
• 46 Sleight E, Coombs RC, Gibson AT, Primhak RA. Neonatal respiratory distress in near-term infants—consider surfactant protein B deficiency. Acta Paediatr 1997; 86 (4) 428-430
• 47 Wallot M, Wagenvoort C, deMello D, Müller KM, Floros J, Roll C. Congenital alveolar proteinosis caused by a novel mutation of the surfactant protein B gene and misalignment of lung vessels in consanguineous kindred infants. Eur J Pediatr 1999; 158 (6) 513-518
• 48 Turcu S, Ashton E, Jenkins L, Gupta A, Mok Q. Genetic testing in children with surfactant dysfunction. Arch Dis Child 2013; 98 (7) 490-495
• 49 Newman B, Kuhn JP, Kramer SS, Carcillo JA. Congenital surfactant protein B deficiency—emphasis on imaging. Pediatr Radiol 2001; 31 (5) 327-331
• 50 King EL, Shackelford GD, Hamvas A. High-frequency oscillation and paralysis stabilize surfactant protein-B—deficient infants. J Perinatol 2001; 21 (7) 421-425
• 51 King E, Shackelford G, Hamvas A. High frequency oscillation with neuromuscular blockade promotes gas exchange in SP-B deficient infants. Am J Respir Crit Care Med 1997; 155: A236
• 52 Hamvas A. Inherited surfactant protein-B deficiency and surfactant protein-C associated disease: clinical features and evaluation. Semin Perinatol 2006; 30 (6) 316-326
• 53 Hamvas A. Evaluation and management of inherited disorders of surfactant metabolism. Chin Med J (Engl) 2010; 123 (20) 2943-2947
• 54 MacLaughlin EF, Woo MS, Horn MV. Lung function changes following infant lung transplantation. Am J Respir Crit Care Med 1996; 153: A657
• 55 Sweet SC, Spray TL, Huddleston CB , et al. Pediatric lung transplantation at St. Louis Children's Hospital, 1990-1995. Am J Respir Crit Care Med 1997; 155 (3) 1027-1035
• 56 Palomar LM, Nogee LM, Sweet SC, Huddleston CB, Cole FS, Hamvas A. Long-term outcomes after infant lung transplantation for surfactant protein B deficiency related to other causes of respiratory failure. J Pediatr 2006; 149 (4) 548-553
• 57 Hamvas A. Surfactant protein B deficiency: insights into inherited disorders of lung cell metabolism. Curr Probl Pediatr 1997; 27 (9) 325-345
• 58 Spray TL, Mallory GB, Canter CB, Huddleston CB. Pediatric lung transplantation. Indications, techniques, and early results. J Thorac Cardiovasc Surg 1994; 107 (4) 990-999 , discussion 999–1000
• 59 Aneja MK, Rudolph C. Gene therapy of surfactant protein B deficiency. Curr Opin Mol Ther 2006; 8 (5) 432-438
• 60 Korst RJ, Bewig B, Crystal RG. In vitro and in vivo transfer and expression of human surfactant SP-A- and SP-B-associated protein cDNAs mediated by replication-deficient, recombinant adenoviral vectors. Hum Gene Ther 1995; 6 (3) 277-287