Biomedical subjects

Annet M Bosch

Publications and source records attributed to Annet M Bosch.

4 recordsLinked to original sources

PubMed2006

Classical galactosaemia revisited.

Classical galactosaemia (McKusick 230400) is an: autosomal recessive disorder of galactose metabolism, caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT; EC 2.7.712). Most patients present in the neonatal period, after ingestion of galactose, with jaundice, hepatosplenomegaly, hepatocellular insufficiency, food intolerance, hypoglycaemia, renal tubular dysfunction, muscle hypotonia, sepsis and cataract. The gold standard for diagnosis of classical galactosaemia is measurement of GALT activity in erythrocytes. Gas-chromatographic determination of urinary sugars and sugar alcohols demonstrates elevated concentrations of galactose and galactitol. The only therapy for patients with classical galactosaemia is a galactose-restricted diet, and initially all galactose must be removed from the diet as soon as the diagnosis is suspected. After the neonatal period, a lactose-free diet is advised in most countries, without restriction of galactose-containing fruit and vegetables. In spite of the strict diet, long-term complications such as retarded mental development, verbal dyspraxia, motor abnormalities and hypergonadotrophic hypogonadism are frequently seen in patients with classical galactosaemia. It has been suggested that these complications may result from endogenous galactose synthesis or from abnormal galactosylation. Novel therapeutic strategies, aiming at the prevention of galactose 1-phosphate production, should be developed. In the meantime, the follow-up protocol for patients with GALT deficiency should focus on early detection, evaluation and, if possible, early intervention in problems of motor, speech and cognitive development.

Bone Density↗

PubMed2005

Identification of novel mutations in classical galactosemia.

Classical galactosemia is an autosomal recessive disorder of galactose metabolism due to galactose-1-phosphate uridyltransferase (GALT) deficiency. Treatment through restriction of dietary galactose intake is lifesaving, but, in spite of this diet, most patients develop abnormalities. In this paper we report the mutational spectrum of classical galactosemia in a cohort of 123 Dutch patients, all with biochemically proven classical galactosemia. In the human GALT gene, which is located on chromosome 9p13, we identified 24 different mutations, including nine mutations that have not been reported previously. The novel mutations include five missense mutations (c.152G>A/p.R51Q, c.404C>T/p.S135W, c.687G>T/p.K229N, c.756G>T/p.Q252H, and c.1140A>C/p.X380C), a frame shift mutation (c.410dupT), a splice site mutation (c.821-2A>G), a possible branch point mutation (c.508-29delT), and a large deletion encompassing at least exons 1-11. Six of these novel mutations were found in patients of Dutch descent: p.R51Q, p.S135W, p.K229N, p.Q252H, p.X380C, and c.410dupT.

Base Sequence↗

PubMed2004

Short-term exogenous galactose supplementation does not influence rate of appearance of galactose in patients with classical galactosemia.

INTRODUCTION: Recently, evidence has been presented that adult patients with classical galactosemia have higher than expected galactose tolerance. This may be caused by a decrease of endogenous galactose production with ageing. Alternatively, suppression of endogenous galactose production by exogenous galactose might be implicated. The aim of this study was to determine if the rate of appearance of galactose is suppressed by exogenous galactose. MATERIALS AND METHODS: Two adult patients with classical galactosemia and three healthy control subjects were given a primed continuous infusion of D-[1-13C]galactose to determine the rate of appearance of galactose (GAR, expressed as micromol/kg/h) before and during additional galactose supplementation. After initial assessment of GAR (GAR1), GAR was determined during doubled (GAR2) or quadrupled (GAR4) galactose infusion. RESULTS: GAR1 was 2.48 and 2.44 in patients 1 and 2, and 0.46, 0.34, and 0.39 in control subjects 1, 2, and 3, respectively. GAR(2) was 2.43 and 2.13 in patients 1 and 2, and 0.57, 0.38, and 0.47 in control subjects 1, 2, and 3, respectively. In patient 1 the experiment was repeated during quadrupled galactose infusion. Here GAR1 was 3.01 and GAR4 was 3.26. CONCLUSIONS: No significant differences between GAR before and during additional galactose infusion were found in patients and in control subjects. GAR1 was significantly higher in patients than in control subjects. We conclude that the rate of appearance of galactose is not influenced by exogenous galactose, at least under short-term conditions, in patients with classical galactosemia and in control subjects.

Adult↗

PubMed2004

Living with classical galactosemia: health-related quality of life consequences.

OBJECTIVE: Classical galactosemia (McKusick 230400) is an autosomal recessive disorder of galactose metabolism caused by a deficiency of galactose-1-phosphate uridyltransferase (EC 2.7.712). Treatment, consisting of a severe restriction of dietary galactose, is life saving, but most patients develop abnormalities despite this diet. The aim of this study was to study the influence of galactosemia on the patients' health-related quality of life (HRQoL), on educational levels, and on the specific galactosemia-related concerns of these families. METHODS: Age-specific HRQoL questionnaires, a classical galactosemia-specific questionnaire designed by the authors, and a list of questions regarding educational attainment were handed out or sent to all 75 members of the Dutch Galactosemia Society and their families. RESULTS: Sixty-three (84%) patients with classical galactosemia from 58 families returned the questionnaire. Concerning HRQoL, significant differences between patients aged 1 to 5 and healthy children were found on the domains of abdominal complaints and communication. Patients aged 8 to 15 years differed from their healthy peers on the domain of cognitive function. Mothers of patients aged 6 to 15 reported a significantly lower HRQoL on the domains of motor and cognitive function. Patients 16 years and older had significant lower scores on the domains of cognitive and social function. The percentage of patients who attend special schools is significantly higher than in the general population, and the educational attainment is significantly lower in patients with classical galactosemia. CONCLUSIONS: This is the first study to describe the HRQoL of patients with classical galactosemia using well-developed and validated instruments in different age groups. The results of the present study indicate that having galactosemia negatively influences the HRQoL. Early and regular evaluation and support of possible cognitive problems should be a major part of the protocol for the follow-up of patients with classical galactosemia.

Adolescent↗