Classic galactosemia: features of diagnosis and treatment

N.O. Pichkur, N.V. Olkhovych, Ya.I. Doronina


Background. Galactosemia type I, or classic galactosemia (CG), is the most severe form of hereditary disorders of carbohydrate metabolism, in particular, galactose. Galactosemia is not included in the program of massive neonatal screening in Ukraine. The CG is characterized by the non-specific onset symptoms and leads to high mortality among infants in the neonatal period. The problem of early diagnosis and treatment of infants with CG in the absence of a program for massive neonatal screening in Ukraine requires solution. The purpose was to analyse the clinical and laboratory, molecular genetic features of patients with CG; to define a set of clinical symptoms and to form selective groups of patients for administration of diet therapy and laboratory diagnosis; to develop schemes-stages of effective early diagnosis and treatment of patients with CG in the absence of mass neonatal screening in order to reduce infant mortality and prevent the disability of patients with this pathology. Materials and methods. In 2014–2017, 317 patients with a diagnosis of hepatitis of uncertain origin were examined. The age of patients ranged from 3 days to 16 years; 145 (45 %) of them were males, 172 (55 %) — females. In all patients, a polysyndromic clinical picture with predominant lesion in the liver function was observed. All patients were examined for the activity of galactose-1-phosphate uridylyltransferase (GALT) enzyme in the red blood cells and underwent DNA diagnosis for the detection of major mutations in the GALT gene. All patients were examined for viral hepatitis, underwent biochemical blood tests for hepatic transaminases, alkaline phosphatase, bilirubin levels, and coagulopathy. Tandem mass spectrometry was also performed to exclude or confirm the metabolic imbalance of amino acids, organic acids, and mitochondrial beta-oxi­dation of fatty acids. Five patients with suspected glycogenosis have been subjected to a quantitative glycogen test in the liver biopsy sample. Results. The diagnosis of CG was established in 15 (5 %) of 317 patients. Male/female ratio was 9 : 6, patient’s age ranged from 14 days to 15 years at the time of investigation in the Center. In 13 out of 15 children, the clinical diagnosis of CG was made on average of 47 days of life (47 ± 15 days). In two patients, the CG was diagnosed at the age of 2 and 15 years. In all patients, the activity of GALT enzyme in erythrocytes was reduced and ranged from 0.08 to 5.8 U/g Hb (mean value 3.3 ± 1.6 U/g Hb) at a normal value > 10 U/g Hb. Molecular genetic analysis was performed in 14 patients. Five patients had a homozygous genotype of Q188R, 1 patient — homozygous K285N genotype, 6 patients were heterozygotes in two major mutations, Q188R and K285N (genotype Q188R/K285N); one patient had р.Y209S/р.K285N genotype, another one — р.K285N mutation only in one allele. Thus, 28 alleles in the GALT gene were examined from 14 patients and 27 mutations were identified: Q188R —57 %, K285N — 36 %, Y209S — 3 % (detected in one patient in one allele). The mutations Q188R and K285N together amounted to 93 % indicating a high level among Ukrainian population. Cataract has been diagnosed in 6 patients (40 %). In our group of CG patients, in all of them it was combined with neurological symptoms. Defeats of the nervous system (cognitive deficiency, spastic tetraparesis, dystonia, tremor and disorders in the form of dysarthria and delayed speech development) were noted in 7 CG patients (47 %). The analysis of the mortality in this group showed that it was 27 % (4 of 15 patients dead at the age of 24 days to 2.5 months). Additionally, the analysis of families with CG patients showed frequent cases of early death from liver failure in the age up to 14 weeks. In three families, there were four deaths in the neonatal period. If we consider all dead children with similar symptoms in the families with CG patients, then the percentage of deceased patients would be 47 % (8 of 19 children born in families with CG). In all cases, treatment was started too late, on average on day 44. Jaundice was observed in 93 % of CG patients, hepatomegaly — in 80 %, dyspeptic manifestations — in 87 %. The scheme has been proposed of stages of diagnostic and therapeutic measures in the selective group with suspected CG. Conclusions. CG is a life-threatening disease characterized by severe hepatocellular lesions, dyspeptic syndrome, sepsis, and high mortality in the neonatal period. Mutations Q188R and K285N together make up 93 % that indicates a high level in Ukraine. All infants with jaundice due to hyperbilirubinemia, hepatomegaly, dyspeptic disorders, high levels of transaminases, and blood clotting disorders should be screened for the presence of CG and urgently change the diet to lactose-free one, until the results of the confirmatory laboratory diagnosis are obtained.


galactosemia; classic galactosemia; activity of GALT enzyme; lactose-free diet


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