Fenugreek odour in maple syrup urine disease. K. Monastiri1*, K. Limame2, N. Kaabachi 3, H. Kharrat 4, S. Bousnina5, H. Pousse6,. M. Radhouane6, M. N. ...
J. Inher. Metab. Dis. 20 (1997) 614– 615 © SSIEM and Kluwer Academic Publishers. Printed in the Netherlands
SHORT REPORT Fenugreek odour in maple syrup urine disease K. Monastiri1*, K. Limame 2, N. Kaabachi 3, H. Kharrat 4, S. Bousnina 5, H. Pousse 6, M. Radhouane6, M. N. Gueddiche 6 and N. Snoussi 1 1
Division of Neonatology of the Department of Obstetrics and Gynecology Sousse; 2Department of Biochemistry, Farhat Hached Hospital, Sousse; 3Department of Biochemistry, La Rabta Hospital, Tunis; 4Department of Pediatrics, Kairouan Hospital; 5Department of Pediatrics, Children’s Hospital of Tunis and 6Department of Pediatrics, Monastir Hospital, Tunisia *Correspondence: Centre de Maternité et de Néonatalogie, 4000 Sousse, Tunisia
Maple syrup urine disease (MSUD; McKusick 24860) is an inborn error of amino acid metabolism characterized by a maple syrup, curry or burnt sugar odour to the urine (Chuang and Shih 1995). It should be noted, however, that since maple syrup is largely unknown by Mediterranean populations, the urine odour is more reminiscent of fenugreek (Trigonella foenum graecum L.) than of maple syrup. Indeed, fenugreek beans are traditionally used by these populations as an infusion for sick persons (Boukef et al 1982) and its fragrant smell is disagreeable and well known in this area. Fenugreek odour in MSUD patients could be explained by the following arguments. (a) 4-Hydroxyisoleucine content in fenugreek beans is high and decreases dramatically when their odour increases (Sauvaire et al 1994). (b) The 3-hydroxy-4,5-dimethyl-2(5H)furanone (HDMF) has been identified as an essential volatile substance that constitutes the fenugreek odour (Tokitomo et al 1980; Girardon 1984). (c) This HDMF and some heterocycles of furanone were identified in food aromas and had the flavour of burnt sugar, curry or maple syrup (Underwood 1971; Rijkens and Boelens 1975). We postulate, then, that the fragrant smell of MSUD patients is related to HDMF or similar heterocycles. Further studies could clarify this hypothesis. Given the poor prognosis of the disease, a rapid identification of the clinical features is necessary. Physicians in Mediterranean countries should keep in mind that a fenugreek odour of urine with neurological distress in newborn infants and without any history of fenugreek ingestion by the mother or the baby indicates a suspicion of MSUD. REFERENCES Boukef MK, Soussi HR, Balansard G (1982) Contribution à l’étude des plantes utilisées en médecine traditionnelle tunisienne. Plantes médicinales et phytothérapie 16(4): 260 – 279. Chuang DT, Shih VE (1995) Disorders of branched chain amino acid and keto acid metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease, 7th edn. New York: McGraw-Hill, 1239 – 1277. Girardon P (1984) Les constituants volatils des graines de Fenugrec et leur contribution à l’arôme. Thèse de 3 ème cycle, Sciences Agronomiques, Montpellier. Rijkens F, Boelens H (1975) The future of aroma research. In: Maarse H, Groenen PJ, eds. Proceedings of International Symposium on Aroma Research. Zeist, Wageningen, 203 – 220. The results of this study were presented at the 9th International Symposium of Neonatal Screening and the second International Society of Neonatal Screening, Lille (France), September 13 – 17, 1993.
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Sauvaire Y, Girardon P, Baccon JC, Risterucci AM (1984) Changes in growth, proteins and free amino acids of developing seed and pod of fenugreek. Phytochemistry 23: 479 – 486. Tokitomo Y, Kobayashi A, Yamanishi T, Muraki S (1980) Studies on the sugary ‘flavor’ of raw cane sugar. III. Key compound of the sugary compound. Proc Jpn Acad Ser. B 56: 457 – 462. Underwood JC (1971) Effect of heat on the flavoring components of maple syrup — a preliminary study by gas chromatography. J Food Sci, 36: 228 – 230.
J. Inher. Metab. Dis. 20 (1997) 615– 616 © SSIEM and Kluwer Academic Publishers. Printed in the Netherlands
SHORT REPORT Two novel mutations in patients with atypical phenotypes of acid sphingomyelinase deficiency H. Pavl˚u and M. Elleder* Institute for Inborn Errors of Metabolism, First Faculty of Medicine, Charles University and the General Faculty Hospital, Prague, Czech Republic *Correspondence: Inst. I.E.M. Division B, U nemocnice 5, 128 53 Prague 2, Czech Republic
To date 13 mutations have been reported in the acid sphingomyelinase (ASM) gene causing type A Niemann–Pick disease (NPD), a severe rapidly progressive neurovisceral storage disease, fatal within early infancy. Five mutations have been identified in type B NPD, a chronic visceral non-neuropathic variant. So far, only one family with the so-called intermediate form of NPD has been analysed for mutations in the ASM gene (reviewed by Vanier and Suzuki 1996). We have studied four Czech NPD patients from three families, exhibiting an atypical intermediate course of the disease (Elleder et al 1986, 1988). Mutations were determined by direct sequencing of genomic PCR products using Sanger’s dideoxy method with T7 polymerase or cycle sequencing protocol with ThermoSequenase (Amersham) on an automated fluorescent sequencer (EMBL, Heidelberg). In two middle-aged brothers (presently aged 32 and 36 years) with similar mild visceral storage but different neurological involvement, stabilized course, severe sphingomyelinase deficiency in vitro but relatively mild deficiency in vivo as sphingomyelin degradation in fibroblasts (Elleder et al 1988), compound heterozygosity was identified. It consisted of a novel T 1022 →C transition in codon 341 (L341P) and of a frameshift mutation fsP330 on the second allele, both within exon 2. The latter has been considered a typical mutation for NPD type A by Levran and colleagues (see Vanier and Suzuki 1996). The remainder of the DNA coding sequence was normal. The L341P and fsP330 alleles were of paternal and maternal origin, respectively. The L341P mutation introduces a novel Sau961 restriction site which was not identified in more than 100 control ASM alleles. In two unrelated patients (T.K., Z. ) with clinical features of B type, minimal neurological lesions but biochemical parameters of type A (Elleder et al 1986), a novel mutation, homoallelic transversion C874 →A, was found in exon 2. This mutation predicted a glutamineto-lysine substitution (Q292K). AvaII restriction analysis confirmed the homoallelic state J. Inher. Metab. Dis. 20 (1997)
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in both patients and the heterozygosity in each parent from one patient and in the mother of the second (the father was not available). The rest of the DNA coding sequence was normal. Since the Q292K mutation did not occur in any of 100 normal ASM alleles, we do not consider it to be a polymorphism. The subsequent clinical courses of the two patients differ. In both patients (aged 13 and 20 years) the visceral manifestation is progressive. In the younger, however, neurological symptoms have become manifest. This work was supported by the Grant Agency of the Czech Republic (grant no. 301/93/0854). REFERENCES Elleder M, Nevoral J, pi áková V, et al (1986) A new variant of sphingomyelinase deficiency (Niemann – Pick): visceromegaly, minimal neurological lesion and low in vivo degradation rate of sphingomyelin. J Inher Metab Dis 9: 357 – 366. Elleder M, ihula J, Sv rák J, Vanier MT (1988) Family with profound sphingomyelinase deficiency resisting closer subclassification. In Salvayre R, Douste-Blazy L, Gatt S, eds. Lipid Storage Disorders. Biological and Medical Aspects. New York: Plenum Press, 153–161. Vanier MT, Suzuki K (1996) Niemann – Pick diseases. In Vinken PJ, Bruyn GW, Moser HW, eds. Neurodystrophies and Neurolipidoses, Handbook of Clinical Neurology, Vol. 66/Revised Series Vol. 22. Amsterdam: Elsevier Science, 133–162.
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