Homozygous pArg610del Mutation Unusually Associated With Severe Delay of Growth in 2 Acid Sphingomyelinase Deficiency-affected Sibs.
Journal
Journal of pediatric hematology/oncology
ISSN: 1536-3678
Titre abrégé: J Pediatr Hematol Oncol
Pays: United States
ID NLM: 9505928
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
pubmed:
15
3
2019
medline:
1
1
2021
entrez:
15
3
2019
Statut:
ppublish
Résumé
Typically, patients with Acid Sphingomyelinase Deficiency (ASMD) because of p.Arg610del mutation, have mild phenotype with normal linear growth. We reported the case of 2 Tunisian brothers who have been referred for splenomegaly, polyadenopathies, pubertal, and growth delay. Molecular testing of SMPD1 gene revealed the presence of a homozygous p.Arg610del mutation. Lysosphingomyelin and its isoform-509 were both increased confirming ASMD for both cases. Growth hormone deficiency was highly suspected but growth hormone response after stimulating tests was acceptable for both patients. There is no correlation between phenotype-genotype in case of p.Arg610del mutation that could be associated to a severe delay of growth.
Sections du résumé
BACKGROUND
Typically, patients with Acid Sphingomyelinase Deficiency (ASMD) because of p.Arg610del mutation, have mild phenotype with normal linear growth.
OBSERVATION
We reported the case of 2 Tunisian brothers who have been referred for splenomegaly, polyadenopathies, pubertal, and growth delay. Molecular testing of SMPD1 gene revealed the presence of a homozygous p.Arg610del mutation. Lysosphingomyelin and its isoform-509 were both increased confirming ASMD for both cases. Growth hormone deficiency was highly suspected but growth hormone response after stimulating tests was acceptable for both patients.
CONCLUSIONS
There is no correlation between phenotype-genotype in case of p.Arg610del mutation that could be associated to a severe delay of growth.
Identifiants
pubmed: 30870388
doi: 10.1097/MPH.0000000000001447
pii: 00043426-202008000-00034
doi:
Substances chimiques
Sphingomyelin Phosphodiesterase
EC 3.1.4.12
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e499-e502Références
Leavitt JA, Kotagal S. The “cherry red” spot. Pediatr Neurol. 2007;37:74–75.
Schuchman EH, Desnick RJ. Types A and B Niemann-Pick disease. Mol Genet Metab. 2017;120:27–33.
Vanier MT, Ferlinz K, Rousson R, et al. Deletion of arginine (608) in acid sphingomyelinase is the prevalent mutation among Niemann-Pick disease type B patients from northern Africa. Hum Genet. 1993;92:325–330.
McGovern MM, Avetisyan R, Sanson BJ, et al. Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD). Orphanet J Rare Dis. 2017;12:41.
Schuchman EH. Acid sphingomyelinase, cell membranes and human disease: lessons from Niemann-Pick disease. FEBS Lett. 2010;584:1895–1900.
Quinn PJ. Sphingolipid symmetry governs membrane lipid raft structure. Biochim Biophys Acta. 2014;1838:1922–1930.
McGovern MM, Dionisi-Vici C, Giugliani R, et al. Consensus recommendation for a diagnostic guideline for acid sphingomyelinase deficiency. Genet Med. 2017;19:967–974.
Cox GF, Clarke LA, Giugliani R, et al. Burden of illness in acid sphingomyelinase deficiency: a retrospective chart review of 100 patients. JIMD Rep. 2018;41:119–129.
McGovern MM, Wasserstein MP, Giugliani R, et al. A prospective, cross-sectional survey study of the natural history of Niemann-Pick disease type B. Pediatrics. 2008;122:e341–e349.
Freitas HMP, Mancano AD, Rodrigues RS, et al. Niemann-Pick disease type B: HRCT assessment of pulmonary involvement. J Bras Pneumol. 2017;43:451–455.
Gelb MH, Scott CR, Turecek F. Newborn screening for lysosomal storage diseases. Clin Chem. 2015;61:335–346.
Polo G, Burlina AP, Kolamunnage TB, et al. Diagnosis of sphingolipidoses: a new simultaneous measurement of lysosphingolipids by LC-MS/MS. Clin Chem Lab Med. 2017;55:403–414.
Pettazzoni M, Froissart R, Pagan C, et al. LC-MS/MS multiplex analysis of lysosphingolipids in plasma and amniotic fluid: A novel tool for the screening of sphingolipidoses and Niemann-Pick type C disease. PLoS One. 2017;12:e0181700.
Zampieri S, Filocamo M, Pianta A, et al. SMPD1 mutation update: database and comprehensive analysis of published and novel variants. Hum Mutat. 2016;37:139–147.
Wasserstein M, Godbold J, McGovern MM. Skeletal manifestations in pediatric and adult patients with Niemann Pick disease type B. J Inherit Metab Dis. 2013;36:123–127.
Wasserstein MP, Larkin AE, Glass RB, et al. Growth restriction in children with type B Niemann-Pick disease. J Pediatr. 2003;142:424–428.
Desnick JP, Kim J, He X, et al. Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease. Mol Med. 2010;16:316–321.
Wraith JE, Jones S. Mucopolysaccharidosis type I. Pediatr Endocrinol Rev. 2014;12(suppl 1):102–106.