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Uva-DARE (Digital Academic Repository) UvA-DARE (Digital Academic Repository) Classical galactosemia revisited Bosch, A.M. Publication date 2004 Link to publication Citation for published version (APA): Bosch, A. M. (2004). Classical galactosemia revisited. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:26 Sep 2021 6 6 Classicall galactosemia versus galactokinase deficiency,, a comparative study with implications forr a potential therapy Partt of this chapter has been published as: Clinical features of galactokinasee deficiency: a review of the literature JJ Inherit Metab Dis 2002; 25:629-34 A.M.. Bosch1-3 H.D.. Bakker1 A.H.. v Gennip2 J.V.. v Kempen4 R.J.A.. Wanders1-2 F.A.. Wijburg1 Fromm the department of Pediatrics and the laboratory Genetic Metabolicc Diseases, Academic Medical Centre, University of Amsterdam;; department of Pediatrics, Gooi-Noord Hospital, Blaricum;; 4Dutch Society for Galactosemia, The Netherlands. Abstract t Galactokinasee deficiency (McKusick 230200) is a rare autosomal recessive inborn error of galactosee metabolism. Cataract and, rarely, pseudotumour cerebri caused by galactitol accumulationn seem to be the only consistently reported abnormalities in this disorder (Holton ett al 2001). We performed a literature search to obtain information on the clinical spectrum off galactokinase deficiency. A total number of 25 publications were traced describing 55 galactokinasee deficient patients. Cataract was reported in most patients. Clinical abnormalities otherr than cataract were reported in 1 5 (35%) out of 43 cases on which information was available.. However, all symptoms were reported infrequently and a causal relationship with thee galactokinase deficiency is unlikely. As indeed cataract and pseudotumor cerebri appearr to be the sole complications of galactokinase deficiency, outcome for patients with galactokinasee deficiency is much better than for patients with classical galactosemia (McKusickk 230400), a more common autosomal recessive disorder of galactose metabolism causedd by galactose-1-phosphate uridyltransferase (GALT;EC 2.7.712) deficiency. Long term follow-upp of patients with this disorder has shown that, in spite of a severe galactose restrictedd diet, most patients develop abnormalities such as a disturbed mental and/or motorr development, dyspraxia and hypergonadotrophic hypogonadism. Endogenous productionn of galactose has been considered an important etiological factor. Althoughh part of the damage in classical galactosemia may already occur in utero, available evidencee suggests that damage will continue after birth. Inhibition of galactokinase may thuss be a promising approach to control damage in GALT deficient patients. 92 2 Classicall galactosemia versus galactokinase deficiency Introduction n Galactokinasee deficiency (McKusick 230200) is a rare autosomal recessive inborn error of galactosee metabolism. In the Leloir pathway, galactokinase (EC 2.7.1.6) catalyses the phosphorylationn of galactose with ATP to galactose-1-phosphate. The disorder was first describedd by Gitzelmann (1965, 1967). The estimated incidence varies. Thalhammer et al (1968)) reported the first case discovered in a newborn screening program after screening 35.7700 neonates for hypergalactosemia. Mayes and Guthrie (1968) determined galactokinase activityy in a mostly Caucasian population and reported an estimated incidence of heterozygotess of 1:107. They concluded that galactokinase deficiency should occur in about 1:: 40,000 to 1: 50,000 births. Levy (1980) however found only six neonates with galactokinasee deficiency after screening 6,000,000 infants for hypergalactosemia. As a numberr of the reported patients were of gypsy ancestry, the incidence may vary among differentt populations (Gitzelmann 1965; Kalaydjieva et al 1999; Linneweh et al 1970; Thalhammerr et al 1968). Stambolian and colleagues (1995) localized the human galactokinasee gene, GK1, to the 17q24 region and many private mutations have been reportedd in galactokinase deficient patients (Hunter et al 2001; Kolosha et al 2000; Stamboliann et al 1995). In Roma patients a founder mutation (P28T) was reported (Kalaydjievaa et al 1999). Cataractt caused by galactitol accumulation seems to be the only consistent abnormality in galactokinasee deficiency (Holton et al 2001) and this can be prevented with a galactose restrictedd diet. However, other abnormalities have been reported in association with galactokinasee deficiency, but it is unclear whether these are a result of galactokinase enzyme deficiencyy (Segal et al 1979). Thiss relatively benign course of the disease is in strong contrast with the high percentage of latee complications such as problems of mental development, verbal dyspraxia and delayed vocabulary,, deficits of cognitive function, disorders of motor function, and hypergonadotrophicc hypogonadism that have been reported in classical galactosemia (Schweitzerr 1993; Waggoner 1990). Nevertheless, since most patients with galactokinase deficiencyy have been reported as isolated patients it is difficult to obtain a good overview of thee pathology. In view of potential therapies for classical galactosemia, aimed at inhibition off galactokinase, we performed a literature search to obtain information on the clinical spectrumm of galactokinase deficiency in comparison with classical galactosemia. Chapterr 6 93 3 Method d AA search was done in EBSCO Medline and PubMed with the terms galactokinase deficiency // human. We searched for publications in English, German, French and Dutch. Only 71 publicationss were retrieved. The abstracts were screened for patient reports. References in Holtonn and colleagues {2001) were checked and publications not previously found in EBSCO Medlinee or PubMed were added. Of all retrieved publications containing clinical information, referencess were carefully checked for additional clinical reports. 94 4 Classicall galactosemia versus galactokinase deficiency Results s AA total number of 25 publications were traced, describing 55 galactokinase deficient patients. Inn all cases the diagnosis was established by demonstrating the deficient activity of the galactokinasee enzyme, usually in erythrocytes. Publications reporting galactokinase variants weree excluded. Some patients have been described in more than one publication. Only the publicationn containing the most clinical information on each patient is included. (Beutierr et al 1973; Borzy et al 1984; Colin et al 1976; Cook et al 1971; Dahlqvist et al 1970;; Gitzelmann 1965, 1967; Kaloud et al 1972; Kalaydjieva et al 1999; Kerr et al 1971; Koloshaa et al 2000; Kurt et al 2002; Levy et al 1972; Linneweh et al 1970; Litmann et al 1975;; Monteleone et al 1971; Olambiwonnu et al 1974; Pickering and Howel 1972; Segal etall 1979; Sitzmann et al 1977; Stambolian etal 1995; Thalhammer et al 1968; Vecchio et all 1976; Vigneron etal 1970; Xu etal 1989). Thee combined results are shown in Table 1. Cataract is a frequent feature in the galactokinase- deficientt patients. Only patients detected by neonatal screening did not suffer from cataract. Clinicall abnormalities other than cataract were reported in 15 (35%) out of 43 cases on whichh information was available. Central nervous system abnormalities (mental retardation, neurofibromatosis,, neurological deterioration, epilepsy and pseudotumor cerebri) were reportedd in 8 (19 %) out of 43 cases. Mental retardation was described in 3 (7%) out of 43 Tablee 1. Family history and Symptoms in galactokinase deficiency Featuree number of cases with feature/ % numberr of informative cases consanguinityy 9/35 26 gypsyy ancestry 11/27 40 cataractt 24/32 75 mentall retardation 3/43 7 epilepsyy 1/43 2 neurologicall deterioration 1/43 2 neurofibromatosiss 1/43 2 pseudotumorr cerebri 2/43 5 asphyxiaa 1/43 2 prematuree birth 1/43 2 smalll for gestational age 3/43 7 failuree to thrive 1/43 2 sloww feeding 1/43 2 hypoglycemiaa 1/43 2 hepatosplenomegalyy 2/43 5 C22 complement deficiency 1/43 2 Chapterr 6 95 5 patients.. Two of them are brothers with cataract, mental retardation and severe speech delay,, reported by Segal (1979). One patient with mild mental retardation was reported by Koloshaa and colleagues (2000). Gitzelmann (1965, 1967; Gitzelmann et al 1974) reported thee first galactokinase deficient patient, a male with galactokinase deficiency and neurofibromatosis.. His mother also suffered from neurofibromatosis. His intelligence was normall and his neurological complications were consistent with the neurofibromatosis. Pickeringg and Howel (1972) described a girl with neurological deterioration after developing severee epilepsy from age 17. She was diagnosed with cataract at age 4 and was treated
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