Galactosemia, congenital
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[MIM 230 200, 230 350, 230 400]
About 1/35,000 newborns in Europe. Autosomal recessive transmission. Enzymatic deficiency in the galactose metabolism (Leloir's pathway).
Neonatal screening is performed in many countries..
Three deficits are possible:
- type I, the most frequent; deficiency in galacto-1-phosphate uridyl transferase (GALT) (9p13) [MIM 230 400],
In the first days of life: lethargy, vomiting, refusal to drink, jaundice with hepatomegaly, edema and ascites. In the absence of treatment, rapid death with hepatocellular failure and gram - (E Coli) sepsis. Nuclear cataract develops in a few days and becomes rapidly irreversible.
- type II, deficiency in galactokinase (GALK) (17q24) [MIM 230 200]; usually, isolated early cataracts, with no other sign of the disease
- type III, deficiency in uridine diphosphate galactose-4-epimerase (UDP) (1p36-p35 or GALE, acronym of GALactose Epimerase deficiency) [MIM 230 350] ; very rare,
Three forms of GALE have been identified:
- generalized form (rare): reduced enzyme activity in all tissues, clinical presentation similar to type I
- peripheral form: enzyme deficiency is limited to red blood cells and leukocytes: patients are generally asymptomatic
- intermediate form: the enzyme deficiency concerns red blood cells and leukocytes, and the enzymatic activity in other tissues is less than 50 % of normal: the clinical presentation is very variable, from asymptomatic to a temporary neonatal form that responds well to the diet. Some cases have thrombocytopenia with dysmegakaryopoiesis and hemolytic anemia
Treatment: galactose-free diet, which means:
- NO breastfeeding. Use of special milk
- a strict diet based on the galactose content of foods (either actual or added-in lactose): vegetables, fruits, etc (see a dietician and list on liste.produits.free.fr)
Lactose and galactose are very often present in the components of many drugs which must therefore be avoided. The amount of galactose contained in the medical drugs is usually low and if a treatment is really necessary (and if there is no alternative without galactose or lactose), the drug can be administered. Saccharin and sucrose are safe. It is always useful to verify the list of excipients of a drug.
Despite a well observed diet, complications can be observed due to deficient or aberrant galactosylation of some proteins or lipids :
- neurological: decrease in IQ, verbal dyspraxia, disorders of myelination
- endocrine: ovarian dysfunction (primary deficiency) with increased FSH and LH
There is a form know as Duarte galactosemia or Swiss galactosemia: those patients present with high blood levels of galactose-1-phosphate but with a sufficient residual enzymatic activity (25 %)of GALT (alactose-1-phosphate uridyl transferase). They are asymptomatic and do not have to follow a specific diet.
Anesthetic implications:
avoid hidden intake lactose and galactose.
References :
- Carlock G, Fisher T, Lynch ME, Potter NL et al.
Developmental outcomes in Duarte galactosemia.
Pediatrics 2019 ; 143 : e 20182516
- Derks B, Demirbas D, Arantes RR, Banford S, Burlina AB, Cabrera A, Chiesa A et al.
Galactose epimerase deficiency : lessons from the GalNet registry.
Orphanet J Rare Diseases 2022 ; 17 : 331 doi 10.1186/s13023-022-02494-4
Updated: September 2022