Galactosemia

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Classification according to ICD-10
E74.2 Galactose metabolism disorders
- galactosemia
ICD-10 online (WHO version 2019)

Galactosemia ( gr. Γαλάκτωσις ( galaktosis ) =, turning to milk 'and gr. Αἷμα ( Haema ) = Blood') is a rare congenital metabolic disorder , is in too much galactose is (simple sugar) in the blood and it also comes to galactosuria .

It is a mutation of the so-called GALT gene the autosomal - recessive inherited is. The GALT gene is located on chromosome 9 in humans . Galactosemia occurs in around one in 40,000 newborns worldwide and was first described in 1917 by Friedrich Göppert (1870–1927).

Classic galactosemia is characterized by the partial or complete absence of the enzyme galactose-1-phosphate uridyl transferase (= galactose transferase, abbr .: GALT), which plays an important role in galactose metabolism. The enzyme deficiency leads to an accumulation of galactose and galactose-1-phosphate in the cells.

examination

The examination for galactosemia is carried out in Germany as part of the newborn screening from the 36th hour of life. To do this, several drops of blood are taken from the heel and the galactose concentration in the blood is determined in a special laboratory ( Beutler test ).

Symptoms

From the second to third day of life, the newborns become weak in drinking, begin to vomit and have severe jaundice (jaundice). They have a septic effect and also frequently suffer from E. coli sepsis. If the milk diet is continued, the severe liver dysfunction will intensify with the laboratory signs of pronounced neonatal jaundice ( bilirubin > 20 mg / dl with predominance of conjugated , direct bilirubin), a coagulation disorder (Quick value <10%, antithrombin III < 10%) and an increase in transaminases (GOT, GPT approx. 100-300 U / l). Clinically, the children bleed longer from the puncture canals, the lens of the eyes becomes cloudy ( cataracts ). Their apathy increases, they deteriorate and eventually die in hepatic coma .

If this critical phase in newborns is survived without a diagnosis, in about 40% of cases there can be disorders in mental (intellectual disability) or physical (motor skills, puberty ) development, concentration disorders , blindness (rare today) and malfunctioning in girls Ovaries come about due to hormone deficiency during puberty (80% of cases).

therapy

The therapy consists of a lifelong lactose-free and low-galactose diet. Foods high in galactose are e.g. B. Milk and dairy products. ( Caution: The commercially available "lactose-free milk" is lactose-free because the lactose has been split into galactose and glucose ; however, because it still contains galactose, it is just as harmful for galactosemia patients as normal milk. Lactose- free milk is for patients with lactose intolerance For newborns this also means giving up breast milk and conventional baby food, which also contains galactose in the form of lactose. Soy-based baby food does not contain lactose.

In legumes ( peanuts , peas ) are contained substances that can be decomposed in the intestine in galactose. In fruits and vegetables galactose is present in free form. But body care products such as creams, soaps and toothpastes also often contain lactose, and attention should be paid to the details of the ingredients.

However, even if the diet is strictly adhered to, developmental disorders due to the endogenous (self-produced) galactose production cannot always be avoided.

variants

The GALT is only one of three enzymes that are involved in the breakdown of galactose. But only the GALT deficiency leads to galactosemia. GAL kinase (GALK) and GAL epimerase (GALE) are also important for galactose metabolism.

Like GALT, GALK or GALE can also be present in too small a quantity in humans. However, they do not lead to a clinical picture as in galactosemia. Nevertheless, they are often also counted as galactosemia - presumably because they affect the breakdown of galactose. This assignment is not entirely correct and years ago led to the introduction of the term “classical galactosemia” for the GALT deficiency. In order to enable the differentiation, the GALK and GALE deficiencies are briefly discussed below.

D2G galactosemia variant

The so-called D2G variant occurs ten times more frequently than the classic galactosemia, so around 200 newborns with this variant can be expected annually in Germany - compared to 20 children with classic galactosemia. These children inherited the so-called Duarte 2 variant (D2 variant) with approx. 25% GALT activity from one parent, and the classic galactosemia gene with 0% activity from the other parent. The galactose-1-phosphate value in the newborn screening is up to 0.3 mg / dl in healthy children, children with classic galactosemia have blood concentrations between 30 and 40 mg / dl, the carriers of the D2G variant between 1 and 6 mg / dl. These children develop normally even under a diet containing galactose and show no abnormalities in liver function or intelligence development . As a rule, you can breastfeed normally, only if the galactose level is above 5 mg / dl you should temporarily switch to dual milk feeding with a galactose-free soy milk for four to six months. When switching to solid food at the latest, there is no need to restrict food, the children and later adults can eat normally.

Galactokinase deficiency

A galactokinase deficiency is much less common than classic galactosemia (1: 150,000 to 1: 1,000,000). The symptoms are nowhere near as varied as in GALT deficiency. The only typical characteristic of the GALK deficiency is - in the absence of treatment or treatment too late - usually bilateral opacity of the lens of the eye. The GALK deficiency is also usually discovered in the newborn screening so that this eye damage can usually be avoided. If the lens has already become cloudy, it can often be reversed if the treatment is carried out consistently. However, people with GALK deficiency have to follow a low-galactose diet just like patients with GALT deficiency.

UDP-galactose-4-epimerase deficiency

In the case of GALE deficiency, the enzyme UDP-glucose-4-epimerase , or GALE for short, is missing , and here too the galactose cannot be completely converted into glucose. The disorder is not so serious, among other things because the body's own galactose does not form or be released. Two forms of GALE deficiency have to be separated from each other:

1. On the one hand, the enzyme deficiency can only occur in the red blood cells. This form of GALE deficiency is also known as the peripheral form. In people with peripheral GALE deficiency, no tissues for which galactose or galactose phosphate would be harmful are affected, which is why they are usually symptom-free, and they do not have to follow a low-galactose diet.

2. If the enzyme deficiency affects not only the red blood cells, but also other cells and tissues of the body, one speaks of a central GALE deficiency. People with central GALE deficiency must follow a low-galactose diet, as do patients with GALT deficiency. This form of GALE deficiency is extremely rare and until recently was only found in fewer than ten patients in the world.

See also

literature

  • F. Goppert: Galactosuria after administration of lactose in congenital, familial chronic liver disease. In: Clinical weekly. 1917; 54, pp. 473-477.

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