Galactosemia is a hereditary disorder of galactose metabolism caused by a deficiency of galactose-1-phosphate uridyltransferase, leading to the accumulation of galactose-1-phosphate and galactitol. Based on erythrocyte and liver enzyme studies, this enzyme has several variants. The liver, kidneys, eye lenses, and brain tissue are the primary affected organs.

bubble_chart Pathogenesis

The metabolism of galactose primarily occurs in the liver, and the process is illustrated in the figure.

Figure: The metabolic process of galactose

Deficiencies in galactokinase, UDP-galactose isomerase, and galactose-1-phosphate uridylyltransferase (especially the latter) can lead to galactosemia. The organotoxic effects are not caused by galactose itself but by its metabolites, such as galactose-1-phosphate and galactitol. Moreover, each component selectively targets specific organs for injury. For instance, galactitol is the primary substance causing internal visual obstruction, while it exhibits minimal toxic effects on the liver and kidneys.

bubble_chart Pathological Changes

Within a few weeks after birth, liver diseases include gall fel stasis, extensive fatty degeneration, and absence of inflammatory cell infiltration. Later, pseudobiliary duct formation and pseudoglandular hyperplasia occur, along with hepatocyte destruction. Pseudoglandular hyperplasia is characteristic of galactosemia but is not specific. As the disease progresses, fine fibrous tissue proliferation appears. Fibrous tissue proliferation begins around the portal area and later extends into the portal region, forming bridging connections. Subsequently, regenerative nodules develop, and the changes resemble those of alcoholic cirrhosis during the process of liver cirrhosis. Throughout the entire pathological process, there is no significant inflammatory cell infiltration.

bubble_chart Clinical Manifestations

The severity of the disease varies greatly. Some infants may develop an acute, fulminant condition immediately after the first feeding, while many others exhibit a subacute progression. Gastrointestinal symptoms include jaundice, loss of appetite, abdominal distension and fullness, diarrhea, vomiting, and hypoglycemia. Ascites may appear around 2 to 5 weeks, and internal visual obstruction can occur within days after birth. If the mother consumes excessive dairy during pregnancy, the infant may present with jaundice immediately after birth.

bubble_chart Auxiliary Examination

Elevated blood and urine galactose levels, hyperchloremic acidosis, proteinuria, aminoaciduria, and hypoglycemia, along with abnormal liver function. Galactosuria can be alleviated by avoiding galactose-containing foods and may disappear within 3-4 days during intravenous nutrition.

bubble_chart Diagnosis

Newborns exhibiting the above clinical manifestations should be monitored for the possibility of this disease. Elevated galactose levels in blood and urine, particularly a positive urine galactose test with a negative glucose oxidase urine glucose test, confirm the diagnosis. If conditions permit, measuring the content of galactose-1-phosphate uridyltransferase in the patient's red blood cells can be performed, as this enzyme is either completely or nearly completely deficient.

bubble_chart Treatment Measures

Early diagnosis should be followed by the elimination of galactose from the diet. Some advocate discontinuing dietary restrictions after the age of 8, but it is generally believed that lifelong adherence is preferable. With timely treatment, conditions such as internal visual obstruction, hepatomegaly, and cirrhosis can be reversed. Importantly, asymptomatic homozygous females may experience elevated blood galactose levels after consuming high-lactose foods, and infants born to these women may develop galactosemia. Particularly for mothers who have previously given birth to infants with galactosemia, galactose intake should be restricted during pregnancy.