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Journal of Inherited Metabolic Disease
Published in: Journal of Inherited Metabolic Disease 1/2015

01-01-2015 | Complex Lipids

Human genetic disorders of sphingolipid biosynthesis

Authors: Leonardo Astudillo, Frédérique Sabourdy, Nicole Therville, Heiko Bode, Bruno Ségui, Nathalie Andrieu-Abadie, Thorsten Hornemann, Thierry Levade

Published in: Journal of Inherited Metabolic Disease | Issue 1/2015

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Abstract

Monogenic defects of sphingolipid biosynthesis have been recently identified in human patients. These enzyme deficiencies affect the synthesis of sphingolipid precursors, ceramides or complex glycosphingolipids. They are transmitted as autosomal recessive or dominant traits, and their resulting phenotypes often replicate the abnormalities seen in murine models deficient for the corresponding enzymes. In quite good agreement with the known critical roles of sphingolipids in cells from the nervous system and the epidermis, these genetic defects clinically manifest as neurological disorders, including paraplegia, epilepsy or peripheral neuropathies, or present with ichthyosis. The present review summarizes the genetic alterations, biochemical changes and clinical symptoms of this new group of inherited metabolic disorders. Hypotheses regarding the molecular pathophysiology and potential treatments of these diseases are also discussed.
Literature
Aleman TS, Soumittra N, Cideciyan AV et al (2009) CERKL mutations cause an autosomal recessive cone-rod dystrophy with inner retinopathy. Invest Ophthalmol Vis Sci 50(12):5944–5954PubMedCrossRef
Ali M, Ramprasad VL, Soumittra N et al (2008) A missense mutation in the nuclear localization signal sequence of CERKL (p. R106S) causes autosomal recessive retinal degeneration. Mol Vis 14:1960–1964PubMedCentralPubMed
Auer-Grumbach M, Bode H, Pieber TR et al (2013) Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a distinct syndromic phenotype. Eur J Med Genet 56(5):266–269PubMedCentralPubMedCrossRef
Auslender N, Sharon D, Abbasi AH, Garzozi HJ, Banin E, Ben-Yosef T (2007) A common founder mutation of CERKL underlies autosomal recessive retinal degeneration with early macular involvement among Yemenite Jews. Invest Ophthalmol Vis Sci 48(12):5431–5438PubMedCrossRef
Avila-Fernandez A, Riveiro-Alvarez R, Vallespin E et al (2008) CERKL mutations and associated phenotypes in seven Spanish families with autosomal recessive retinitis pigmentosa. Invest Ophthalmol Vis Sci 49(6):2709–2713PubMedCrossRef
Bayes M, Goldaracena B, Martinez-Mir A et al (1998) A new autosomal recessive retinitis pigmentosa locus maps on chromosome 2q31-q33. J Med Genet 35(2):141–145PubMedCentralPubMedCrossRef
Bejaoui K, Uchida Y, Yasuda S et al (2002) Hereditary sensory neuropathy type 1 mutations confer dominant negative effects on serine palmitoyltransferase, critical for sphingolipid synthesis. J Clin Invest 110(9):1301–1308PubMedCentralPubMedCrossRef
Bejaoui K, Wu C, Scheffler MD et al (2001) SPTLC1 is mutated in hereditary sensory neuropathy, type 1. Nat Genet 27(3):261–262PubMedCrossRef
Ben-David O, Pewzner-Jung Y, Brenner O et al (2011) Encephalopathy caused by ablation of very long acyl chain ceramide synthesis may be largely due to reduced galactosylceramide levels. J Biol Chem 286(34):30022–30033PubMedCentralPubMedCrossRef
Boccuto L, Aoki K, Flanagan-Steet H et al (2013) A mutation in a ganglioside biosynthetic enzyme, ST3GAL5, results in salt & pepper syndrome, a neurocutaneous disorder with altered glycolipid and glycoprotein glycosylation. Hum Mol Genet 23(2):418–433PubMedCrossRef
Boukhris A, Schule R, Loureiro JL et al (2013) Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia. Am J Hum Genet 93(1):118–123PubMedCentralPubMedCrossRef
Brown KE, Anderson SM, Young NS (1993) Erythrocyte P antigen: cellular receptor for B19 parvovirus. Science 262(5130):114–117PubMedCrossRef
Cao L, Huang XJ, Chen CJ, Chen SD (2013) A rare family with Hereditary Spastic Paraplegia Type 35 due to novel FA2H mutations: a case report with literature review. J Neurol Sci 329(1–2):1–5PubMedCrossRef
Chiavegatto S, Sun J, Nelson RJ, Schnaar RL (2000) A functional role for complex gangliosides: motor deficits in GM2/GD2 synthase knockout mice. Exp Neurol 166(2):227–234PubMedCrossRef
Citterio A, Arnoldi A, Panzeri E et al (2014) Mutations in CYP2U1, DDHD2 and GBA2 genes are rare causes of complicated forms of hereditary spastic paraparesis. J Neurol 261(2):373–381PubMedCrossRef
Cox TM, Cachon-Gonzalez MB (2012) The cellular pathology of lysosomal diseases. J Pathol 226(2):241–254PubMedCrossRef
Cuadros R, Montejo de Garcini E, Wandosell F, Faircloth G, Fernandez-Sousa JM, Avila J (2000) The marine compound spisulosine, an inhibitor of cell proliferation, promotes the disassembly of actin stress fibers. Cancer Lett 152(1):23–29PubMedCrossRef
Davidson G, Murphy S, Polke J et al (2012) Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort. J Neurol 259(8):1673–1685PubMedCentralPubMedCrossRef
Dawkins JL, Hulme DJ, Brahmbhatt SB, Auer-Grumbach M, Nicholson GA (2001) Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nat Genet 27(3):309–312PubMedCrossRef
Dick KJ, Eckhardt M, Paisan-Ruiz C et al (2010) Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35). Hum Mutat 31(4):E1251–1260PubMedCrossRef
Donkervoort S, Dastgir J, Hu Y et al (2014) Phenotypic variability of a likely FA2H founder mutation in a family with complicated hereditary spastic paraplegia. Clin Genet 85(4):393–395PubMedCrossRef
Dyck PJ (1993) Neuronal atrophy and degeneration predominantly affecting peripheral sensory and autonomic neurons. In P J Dyck, K P Thomas, J W Griffin, P A Low, & J F Poduslo (Eds), Peripheral Neuropathy (3rd Editio, pp 1065–1093) Saunders Philladelphia
Eckl KM, Tidhar R, Thiele H et al (2013) Impaired epidermal ceramide synthesis causes autosomal recessive congenital ichthyosis and reveals the importance of ceramide acyl chain length. J Invest Dermatol 133(9):2202–2211PubMedCrossRef
Edvardson S, Hama H, Shaag A et al (2008) Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia. Am J Hum Genet 83(5):643–648PubMedCentralPubMedCrossRef
Farukhi F, Dakkouri C, Wang H, Wiztnitzer M, Traboulsi EI (2006) Etiology of vision loss in ganglioside GM3 synthase deficiency. Ophthalmic Genet 27(3):89–91PubMedCrossRef
Fishman PH, Max SR, Tallman JF, Brady RO, Maclaren NK, Cornblath M (1975) Deficient Ganglioside Biosynthesis: a novel human sphingolipidosis. Science 187(4171):68–70PubMedCrossRef
Fragaki K, Ait-El-Mkadem S, Chaussenot A et al (2013) Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency. Eur J Hum Genet 21(5):528–534PubMedCentralPubMedCrossRef
Furukawa K, Iwamura K, Uchikawa M et al (2000) Molecular basis for the p phenotype. Identification of distinct and multiple mutations in the alpha 1,4-galactosyltransferase gene in Swedish and Japanese individuals. J Biol Chem 275(48):37752–37756PubMedCrossRef
Futerman AH, van Meer G (2004) The cell biology of lysosomal storage disorders. Nat Rev Mol Cell Biol 5(7):554–565PubMedCrossRef
Garanto A, Vicente-Tejedor J, Riera M et al (2012) Targeted knockdown of Cerkl, a retinal dystrophy gene, causes mild affectation of the retinal ganglion cell layer. Biochim Biophys Acta 1822(8):1258–1269PubMedCrossRef
Garofalo K, Penno A, Schmidt BP et al (2011) Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. J Clin Invest 121(12):4735–4745PubMedCentralPubMedCrossRef
Garone C, Pippucci T, Cordelli DM et al (2011) FA2H-related disorders: a novel c.270 + 3A > T splice-site mutation leads to a complex neurodegenerative phenotype. Dev Med Child Neurol 53(10):958–961PubMedCrossRef
Graf C, Niwa S, Muller M, Kinzel B, Bornancin F (2008) Wild-type levels of ceramide and ceramide-1-phosphate in the retina of ceramide kinase-like-deficient mice. Biochem Biophys Res Commun 373(1):159–163PubMedCrossRef
Hammer MB, Eleuch-Fayache G, Schottlaender LV et al (2013) Mutations in GBA2 cause autosomal-recessive cerebellar ataxia with spasticity. Am J Hum Genet 92(2):245–251PubMedCentralPubMedCrossRef
Hanada K (2003) Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism. Biochim Biophys Acta 1632(1–3):16–30PubMedCrossRef
Harlalka GV, Lehman A, Chioza B et al (2013) Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside biosynthesis. Brain 136(Pt 12):3618–3624PubMedCentralPubMedCrossRef
Harris PA, Roman GK, Moulds JJ, Bird GW, Shah NG (1982) An inherited RBC characteristic, NOR, resulting in erythrocyte polyagglutination. Vox Sang 42(3):134–140PubMedCrossRef
Hellberg A, Poole J, Olsson ML (2002) Molecular basis of the globoside-deficient P (k) blood group phenotype. Identification of four inactivating mutations in the UDP-N-acetylgalactosamine: globotriaosylceramide 3-beta-N-acetylgalactosaminyltransferase gene. J Biol Chem 277(33):29455–29459PubMedCrossRef
Hellberg A, Ringressi A, Yahalom V, Safwenberg J, Reid ME, Olsson ML (2004) Genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood group system and collection. Br J Haematol 125(4):528–536PubMedCrossRef
Hellberg A, Schmidt-Melbye AC, Reid ME, Olsson ML (2008) Expression of a novel missense mutation found in the A4GALT gene of Amish individuals with the p phenotype. Transfusion 48(3):479–487PubMedCrossRef
Hellberg A, Steffensen R, Yahalom V et al (2003) Additional molecular bases of the clinically important p blood group phenotype. Transfusion 43(7):899–907PubMedCrossRef
Huehne K, Zweier C, Raab K et al (2008) Novel missense, insertion and deletion mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) associated with congenital insensitivity to pain with anhidrosis. Neuromuscul Disord 18(2):159–166PubMedCrossRef
Imgrund S, Hartmann D, Farwanah H et al (2009) Adult ceramide synthase 2 (CERS2)-deficient mice exhibit myelin sheath defects, cerebellar degeneration, and hepatocarcinomas. J Biol Chem 284(48):33549–33560PubMedCentralPubMedCrossRef
Jennemann R, Rabionet M, Gorgas K et al (2012) Loss of ceramide synthase 3 causes lethal skin barrier disruption. Hum Mol Genet 21(3):586–608PubMedCrossRef
Keusch JJ, Manzella SM, Nyame KA, Cummings RD, Baenziger JU (2000) Cloning of Gb3 synthase, the key enzyme in globo-series glycosphingolipid synthesis, predicts a family of alpha 1, 4-glycosyltransferases conserved in plants, insects, and mammals. J Biol Chem 275(33):25315–25321PubMedCrossRef
Koda Y, Soejima M, Sato H, Maeda Y, Kimura H (2002) Three-base deletion and one-base insertion of the alpha (1,4) galactosyltransferase gene responsible for the P phenotype. Transfusion 42(1):48–51PubMedCrossRef
Kojima Y, Fukumoto S, Furukawa K et al (2000) Molecular cloning of globotriaosylceramide/CD77 synthase, a glycosyltransferase that initiates the synthesis of globo series glycosphingolipids. J Biol Chem 275(20):15152–15156PubMedCrossRef
Kruer MC, Paisan-Ruiz C, Boddaert N et al (2010) Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA). Ann Neurol 68(5):611–618PubMedCrossRef
Kusnierz-Alejska G, Duk M, Storry JR et al (1999) NOR polyagglutination and Sta glycophorin in one family: relation of NOR polyagglutination to terminal alpha-galactose residues and abnormal glycolipids. Transfusion 39(1):32–38PubMedCrossRef
Laurá M, Eichler F, Hornemann T, et al (2012) Hereditary sensory and autonomic neuropathy type 1: correlation of severity and plasma atypical deoxy-sphyngoid bases. J Neurol Neurosurg Psychiatry 2012 83 (e1)
Liao X, Luo Y, Zhan Z, et al (2013) SPG35 contributes to the second common subtype of AR-HSP in China: frequency analysis and functional characterization of FA2H gene mutations. Clin Genet
Lingwood CA, Law H, Richardson S et al (1987) Glycolipid binding of purified and recombinant Escherichia coli produced verotoxin in vitro. J Biol Chem 262(18):8834–8839PubMed
Littink KW, Koenekoop RK, van den Born LI et al (2010) Homozygosity mapping in patients with cone-rod dystrophy: novel mutations and clinical characterizations. Invest Ophthalmol Vis Sci 51(11):5943–5951PubMedCentralPubMedCrossRef
Liu Y, Su Y, Wiznitzer M, Epifano O, Ladisch S (2008) Ganglioside depletion and EGF responses of human GM3 synthase-deficient fibroblasts. Glycobiology 18(8):593–601PubMedCrossRef
Liu YC, Zheng L, Liu Y et al (2013) Pedigree investigation and genetic analysis of a case with p blood group. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 30(6):736–738PubMed
Lund N, Olsson ML, Ramkumar S et al (2009) The human P (k) histo-blood group antigen provides protection against HIV-1 infection. Blood 113(20):4980–4991PubMedCrossRef
Martin E, Schule R, Smets K et al (2013) Loss of function of glucocerebrosidase GBA2 is responsible for motor neuron defects in hereditary spastic paraplegia. Am J Hum Genet 92(2):238–244PubMedCentralPubMedCrossRef
Mizutani Y, Kihara A, Igarashi Y (2006) LASS3 (longevity assurance homologue 3) is a mainly testis-specific (dihydro) ceramide synthase with relatively broad substrate specificity. Biochem J 398(3):531–538PubMedCentralPubMedCrossRef
Mosbech M, Olsen A, Neess D, et al (2014) Reduced ceramide synthase 2 activity causes progressive myoclonic epilepsy. Ann Clin Transl Neurol in press
Murphy SM, Ernst D, Wei Y et al (2013) Hereditary sensory and autonomic neuropathy type 1 (HSANI) caused by a novel mutation in SPTLC2. Neurology 80(23):2106–2111PubMedCentralPubMedCrossRef
Niimi K, Nishioka C, Miyamoto T et al (2011) Impairment of neuropsychological behaviors in ganglioside GM3-knockout mice. Biochem Biophys Res Commun 406(4):524–528PubMedCrossRef
Nishiguchi KM, Tearle RG, Liu YP et al (2013) Whole genome sequencing in patients with retinitis pigmentosa reveals pathogenic DNA structural changes and NEK2 as a new disease gene. Proc Natl Acad Sci U S A 110(40):16139–16144PubMedCentralPubMedCrossRef
Okuda T, Tokuda N, Numata S et al (2006) Targeted disruption of Gb3/CD77 synthase gene resulted in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins. J Biol Chem 281(15):10230–10235PubMedCrossRef
Penno A, Reilly MM, Houlden H et al (2010) Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids. J Biol Chem 285(15):11178–11187PubMedCentralPubMedCrossRef
Pewzner-Jung Y, Ben-Dor S, Futerman AH (2006) When do Lasses (longevity assurance genes) become CerS (ceramide synthases)? Insights into the regulation of ceramide synthesis. J Biol Chem 281(35):25001–25005PubMedCrossRef
Pewzner-Jung Y, Brenner O, Braun S et al (2010a) A critical role for ceramide synthase 2 in liver homeostasis: II. insights into molecular changes leading to hepatopathy. J Biol Chem 285(14):10911–10923PubMedCentralPubMedCrossRef
Pewzner-Jung Y, Park H, Laviad EL et al (2010b) A critical role for ceramide synthase 2 in liver homeostasis: I. alterations in lipid metabolic pathways. J Biol Chem 285(14):10902–10910PubMedCentralPubMedCrossRef
Pierson TM, Simeonov DR, Sincan M et al (2012) Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration. Eur J Hum Genet 20(4):476–479PubMedCentralPubMedCrossRef
Radner FP, Marrakchi S, Kirchmeier P et al (2013) Mutations in CERS3 cause autosomal recessive congenital ichthyosis in humans. PLoS Genet 9(6):e1003536PubMedCentralPubMedCrossRef
Rautenstrauss B, Neitzel B, Muench C, Haas J, Holinski-Feder E (2009) Late onset hereditary sensory neuropathy type 1 (HSN1) caused by a novel p. C133R missense mutation in SPTLC1. Würzburg, Germany. In: 2009 Meeting of the Peripheral Nerve Society July 4–8, 2009 (p 290 of 381)
Rotthier A, Auer-Grumbach M, Janssens K et al (2010) Mutations in the SPTLC2 subunit of serine palmitoyltransferase cause hereditary sensory and autonomic neuropathy type I. Am J Hum Genet 87(4):513–522PubMedCentralPubMedCrossRef
Rotthier A, Baets J, De Vriendt E et al (2009) Genes for hereditary sensory and autonomic neuropathies: a genotype-phenotype correlation. Brain 132(Pt 10):2699–2711PubMedCentralPubMedCrossRef
Rotthier A, Baets J, Timmerman V, Janssens K (2012) Mechanisms of disease in hereditary sensory and autonomic neuropathies. Nat Rev Neurol 8(2):73–85PubMedCrossRef
Rotthier A, Penno A, Rautenstrauss B et al (2011) Characterization of two mutations in the SPTLC1 subunit of serine palmitoyltransferase associated with hereditary sensory and autonomic neuropathy type I. Hum Mutat 32(6):E2211–2225PubMedCrossRef
Rupps R, Hukin J, Balicki M, Mercimek-Mahmutoglu S, Rolfs A, Dias C (2013) Novel Mutations in FA2H-Associated Neurodegeneration: An Underrecognized Condition? J Child Neurol 28(11):1500–1504PubMedCrossRef
Sabourdy F, Kedjouar B, Sorli SC et al (2008) Functions of sphingolipid metabolism in mammals–lessons from genetic defects. Biochim Biophys Acta 1781(4):145–183PubMedCrossRef
Sheikh KA, Sun J, Liu Y et al (1999) Mice lacking complex gangliosides develop Wallerian degeneration and myelination defects. Proc Natl Acad Sci U S A 96(13):7532–7537PubMedCentralPubMedCrossRef
Simpson MA, Cross H, Proukakis C et al (2004) Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase. Nat Genet 36(11):1225–1229PubMedCrossRef
Steffensen R, Carlier K, Wiels J et al (2000) Cloning and expression of the histo-blood group Pk UDP-galactose: Ga1beta-4G1cbeta1-cer alpha1, 4-galactosyltransferase. Molecular genetic basis of the p phenotype. J Biol Chem 275(22):16723–16729PubMedCrossRef
Suchanowska A, Kaczmarek R, Duk M et al (2012) A single point mutation in the gene encoding Gb3/CD77 synthase causes a rare inherited polyagglutination syndrome. J Biol Chem 287(45):38220–38230PubMedCentralPubMedCrossRef
Suh BC, Hong YB, Nakhro K, Nam SH, Chung KW, Choi BO (2013) Early-onset severe hereditary sensory and autonomic neuropathy type 1 with S331F SPTLC1 mutation. Mol Med Rep 9(2):481–486PubMed
Suh BC, Hong YB, Nakhro K, Nam SH, Chung KW, Choi BO (2014) Early-onset severe hereditary sensory and autonomic neuropathy type 1 with S331F SPTLC1 mutation. Mol Med Rep 9(2):481–486PubMed
Takamiya K, Yamamoto A, Furukawa K et al (1996) Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides but exhibit only subtle defects in their nervous system. Proc Natl Acad Sci U S A 93(20):10662–10667PubMedCentralPubMedCrossRef
Tang Z, Wang Z, Wang Z, Ke T, Wang QK, Liu M (2009) Novel compound heterozygous mutations in CERKL cause autosomal recessive retinitis pigmentosa in a nonconsanguineous Chinese family. Arch Ophthalmol 127(8):1077–1078PubMedCrossRef
Teufel A, Maass T, Galle PR, Malik N (2009) The longevity assurance homologue of yeast lag1 (Lass) gene family (review). Int J Mol Med 23(2):135–140PubMed
Thuresson B, Westman JS, Olsson ML (2011) Identification of a novel A4GALT exon reveals the genetic basis of the P1/P2 histo-blood groups. Blood 117(2):678–687PubMedCrossRef
Tonelli A, D’Angelo MG, Arrigoni F et al (2012) Atypical adult onset complicated spastic paraparesis with thin corpus callosum in two patients carrying a novel FA2H mutation. Eur J Neurol 19(11):e127–129PubMedCrossRef
Tuson M, Marfany G, Gonzalez-Duarte R (2004) Mutation of CERKL, a novel human ceramide kinase gene, causes autosomal recessive retinitis pigmentosa (RP26). Am J Hum Genet 74(1):128–138PubMedCentralPubMedCrossRef
Verhoeven K, Coen K, De Vriendt E et al (2004) SPTLC1 mutation in twin sisters with hereditary sensory neuropathy type I. Neurology 62(6):1001–1002PubMedCrossRef
Vanni N, Fruscione F, Ferlazzo E et al. (2014) Impairment of ceramide synthesis causes a novel progressive myoclonus epilepsy. Ann Neurol (in press)
Votsi C, Zamba-Papanicolaou E, Middleton LT, Pantzaris M, Christodoulou K (2014) A novel GBA2 gene missense mutation in spastic ataxia. Ann Hum Genet 78(1):13–22PubMedCrossRef
Wakil SM, Monies DM, Ramzan K, et al (2013) Novel B4GALNT1 mutations in a complicated form of hereditary spastic paraplegia. Clin Genet
Wang H, Bright A, Xin B, Bockoven JR, Paller AS (2013) Cutaneous dyspigmentation in patients with ganglioside GM3 synthase deficiency. Am J Med Genet A 161A(4):875–879PubMedCrossRef
Wang YC, Chang CF, Lin HC et al (2011) Functional characterisation of a complex mutation in the alpha (1,4) galactosyltransferase gene in Taiwanese individuals with p phenotype. Transfus Med 21(2):84–89PubMedCrossRef
Wei L, Ji YL, Luo H et al (2012) Serological and genetic study of a pedigree featuring a rare p phenotype. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 29(6):701–704PubMed
Westman JS, Hellberg A, Peyrard T, Hustinx H, Thuresson B, Olsson ML (2013) P1/P2 genotyping of known and novel null alleles in the P1PK and GLOB histo-blood group systems. Transfusion 53(11 Suppl 2):2928–2939PubMed
Wilkinson PA, Simpson MA, Bastaki L et al (2005) A new locus for autosomal recessive complicated hereditary spastic paraplegia (SPG26) maps to chromosome 12p11.1-12q14. J Med Genet 42(1):80–82PubMedCentralPubMedCrossRef
Yamashita T, Hashiramoto A, Haluzik M et al (2003) Enhanced insulin sensitivity in mice lacking ganglioside GM3. Proc Natl Acad Sci U S A 100(6):3445–3449PubMedCentralPubMedCrossRef
Yan LX, Zhu FM, Xu XG, Hong XZ (2003) One base deletion of the alpha (1,4) galactosyltransferase gene responsible for p phenotype. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 20(6):495–498PubMed
Yildiz Y, Matern H, Thompson B et al (2006) Mutation of beta-glucosidase 2 causes glycolipid storage disease and impaired male fertility. J Clin Invest 116(11):2985–2994PubMedCentralPubMedCrossRef
Yoshikawa M, Go S, Takasaki K et al (2009) Mice lacking ganglioside GM3 synthase exhibit complete hearing loss due to selective degeneration of the organ of Corti. Proc Natl Acad Sci U S A 106(23):9483–9488PubMedCentralPubMedCrossRef
Zitomer NC, Mitchell T, Voss KA et al (2009) Ceramide synthase inhibition by fumonisin B1 causes accumulation of 1-deoxysphinganine: a novel category of bioactive 1-deoxysphingoid bases and 1-deoxydihydroceramides biosynthesized by mammalian cell lines and animals. J Biol Chem 284(8):4786–4795PubMedCentralPubMedCrossRef
Zoller I, Meixner M, Hartmann D et al (2008) Absence of 2-hydroxylated sphingolipids is compatible with normal neural development but causes late-onset axon and myelin sheath degeneration. J Neurosci 28(39):9741–9754PubMedCrossRef
Zuellig RA, Hornemann T, Othman A et al (2014) Deoxysphingolipids, novel biomarkers for type 2 diabetes, are cytotoxic for insulin-producing cells. Diabetes 63(4):1326–1339PubMedCrossRef
Metadata
Title
Human genetic disorders of sphingolipid biosynthesis
Authors
Leonardo Astudillo
Frédérique Sabourdy
Nicole Therville
Heiko Bode
Bruno Ségui
Nathalie Andrieu-Abadie
Thorsten Hornemann
Thierry Levade
Publication date
01-01-2015
Publisher
Springer Netherlands
Published in
Journal of Inherited Metabolic Disease / Issue 1/2015
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI
https://doi.org/10.1007/s10545-014-9736-1

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