Abstract
In a retrospective study 134 galactosaemic patients, born between 1955 and 1989 in the Federal Republic of Germany were traced and their long-term outcome evaluated. We investigated 83 galactosaemic patients (78 homozygotes, 5 compound heterozygotes) by clinical, psychometric and laboratory testing; 31 patients were evaluated by medical history, the remaining 20 patients had died due to sequelae of the underlying disease. In 48 out of 78 classical galactosaemia patients galactose-free therapy had been started before the 15th day, in 19 between days 15 and 56 and in 11 patients after the 56th day. Physical findings revealed that puberty was delayed in 1 out of 18 males and 6 out of 11 females. Neurological abnormalities included ataxia (n=6), intention tremor (n=11) and microcephaly (n=10). Speech abnormalities were found in 43 out of 66 patients over 3 years of age and disturbance of visual perception and/or arithmetic deficits in 29. Intelligence declined with age, i.e., a DQ or IQ less than 85 was found in 4 out of 34 patients less than 6 years of age (12%), in 10 out of 18 between 7 and 12 years (56%) and in 20 out of 24 older than 12 years (83%). Metabolite patterns (RBC galactose-1-phosphate and UDP-galactose, plasma and urinary galactitol) did not correlate with DQ or IQ. Dietary compliance was good in almost all patients. Compound heterozygotes (n=5) had normal mental and growth development and all laboratory parameters were in the normal range. The cause of the unsatisfactory outcome of well-treated galactosaemic patients with disturbances in long-term development remains unclear. This could be due to a chronic intoxication of galactose metabolites or a deficiency of UDP-galactose or galactose-containing glycoproteins or glycolipids.
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Abbreviations
- G-G:
-
classical galactosaemia
- D2-G:
-
compound heterozygosity
References
Anonymous (1982) Clouds over galactosemia. Lancet II: 1379–1380
Böhles H, Wenzel D, Shin YS (1986) Progressive cerebellar and extrapyramidal motor disturbances in galactosaemic twins. Eur J Pediatr 145: 413–417
Crome L (1962) A case of galactosaemia with the pathological and neuropathological findings. Arch Dis Child 415–421
Donnell GN, Collado M, Koch R (1961) Growth and development of children with galactosemia. J Pediatr 58 (6): 836–844
Fishler K, Koch R, Donnell GN, Wenz E (1980) Developmental aspects of galactosemia from infancy to childhood. Clin Pediatr 19 (1): 38–44
Fraser IS, Russell P, Greco S, Robertson DM (1986) Resistant ovary syndrome and premature ovarian failure in young women with galactosaemia. Clin Reprod Fertil 4: 133–138
Gitzelmann R, Steinmann B (1984) Galactosemia: How does long-term treatment change the outcome? Enzyme 32: 37–46
Haberland C, Perou M, Brunngraber EG (1971) The neuropathology of galactosemia. A histopathological and biochemical study. J Neuropath Exp Neurol 30: 431–447
Holton JB (1990) Galactose disorders: an overview. J Inherited Metab Dis 13: 476–486
Jakobs C, Warner TG, Sweetman L, Nyhan WL (1984) Stable isotope dilution analysis of galactiol, in amniotic fluid: an accurate approach to the prenatal diagnosis of galactosemia. Pediatr Res 18: 714–718
Jan JE, Wilson RA (1973) Unusual late neurological sequelae in galactosaemia. Dev Med Child Neurol 15: 72–74
Jansen G, Muskiet FAJ, Schierbeek H, Berger R, Slik W van den (1986) Capillary gas chromatography profiling of urinary plasma and erythrocyte sugars and polyols as their trimethylsilyl derivatives, preceded by a simple and rapid prepurification method. Clin Chim Acta 157: 277–294
Kaufman FR, Kogut MD, Donnell GN, Goebelsmann U, March C, Koch R (1981) Hypergonadotropic hypogonadism in female patients with galactosemia. N Engl J Med 304: 994–998
Kaufman FR, Xu YK, Ng WG, Donnell GN (1988) Correlation of ovarian function with galactose-1-phosphate uridyl transferase levels in galactosemia. J Pediatr 112 (5): 754–756
Kaufman F, Ng W, Xu YK, et al (1990) Treatment with oral uridine in classical galactosemia (G). Vth International Congress Inborn Errors of Metabolism (abstract). Asilamar, USA W5.7
Kirkman HN (1991) Uridine diphosphate glucose and uridine diphosphate galactose in galactosemia (letter). J Pediatr 119: 329
Komrower GM (1982) Galactosaemia — thirty years on. The experience of a generation F.P. Hudson Memorial Lecture J Inherited Metab Dis 5 [Suppl 2]: 96–104
Komrower GM, Lee DH (1970) Long-term follow-up of galactosemia. Arch Dis Child 45: 367–373
Lo WL, Packman S, Nash SN, et al (1984) Curious neurologic sequelae in galactosemia. Pediatrics 73(3): 309–312
Ng WG, Xu YK, Kaufman F, Donnell GN (1991) Uridine diphosphate glucose and uridine diphosphate galactose in galactosemia (reply). J Pediatr 119: 329–331
Ng WG, Xu YK, Kaufman FR, Donnell GN (1989) Deficit of uridine diphosphate galactose in galactosemia. J Inherited Metab Dis 12: 257–266
Palmieri MJ, Berry GT, Player DA, Rogers S, Segal S (1991) The concentration of red blood cell UDPglucose and UDPgalactose determined by high-performance liquid chromatography. Anal Biochem 194: 388–393
Petry K, Greinix HT, Nudelman E, et al (1991) Characterization of a novel biochemical abnormality in galactosemia: deficiency of glycolipids containing galactose or N-acetylgalactosamine and accumulation of precursors in brain and lymphocytes. Biochem Med Metab Biol 46: 93–104
Prader A, Largo RH, Molinari L, Issler C (1988) Physical growth of Swiss children from birth to 20 years of age. Helv Paediatr Acta 43 [Suppl 52]: 1
Shin YS (1991) Galactose metabolism and disorders of galactose metabolism. In: Hommes FA (ed) Techniques in diagnostic human biochemical genetics: a laboratory manual). Wiley-Liss Inc., New York, pp 267–283.
Shin-Buehring YS, Beier T, Tan A, Osang M, Schaub J (1977) The activity of galactose-1-phosphate uridyltransferase and galactokinase in human fetal organs. Pediatr Res 11: 1003–1009
Shin-Bühring YS, Osang M, Ziegler R, Schaub J (1977) A simple method for galactose-1-phosphate uridyltransferase assay and the separation of its isoenzymes by DEAE-cellulose column chromatography. Clin Chim Acta 74: 1–5
Tanner JM, Whitehouse RH (1976) Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 51: 170–179
Waggoner DD, Buist NR, Donnell GN (1990) Long-term prognosis in galactosaemia: results of a survey of 350 cases. J Inherited Metab Dis 13: 802–818
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This study was supported by a grant from the “Stifterverband für die Deutsche Wissenschaft” (Huebner-stiftung), grant TS 114/18/89 and by the “Arbeitsgemeinschaft für Pädiatrische Stoffwechselstörungen”
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Schweitzer, S., Shin, Y., Jakobs, C. et al. Long-term outcome in 134 patients with galactosaemia. Eur J Pediatr 152, 36–43 (1993). https://doi.org/10.1007/BF02072514
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DOI: https://doi.org/10.1007/BF02072514