Objective. Hemochromatosis (HH) is an autosomal recessive hereditary disease caused by excessive accumulation of iron (Fe) in the body.

Gene penetrance in HH is not high, in addition to the classic clinical picture of HH, asymptomatic patients are also increasing. Almost 50 % of C282Y homozygotes do not experience progressive Fe accumulation and therefore do not meet the clinical criteria for HH. On the other hand, about 15 – 20 % of patients with clinically defined HH do not have the C282Y homozygous mutation. It can be heterozygotes or mixed heterozygotes, or another so far unknown genetic deviation with a similar phenotype, or a so far unrecognized secondary accumulation of iron (hemosiderosis).

Patients and methods. In the examined group of 52 patients (29 men and 23 women) with clinical manifestations indicative of HH, standard hematological and biochemical examination, transferrin saturation (ST), ferritin (FER) examination, abdominal ultrasonography and genetic examination were performed. Of these, a genetic mutation was confirmed in 35 patients, in homozygous form of mutation in 17 % (9 patients). Of these, 5 patients had the H63D mutation (56 % of homozygotes) and 4 patients had the C282Y mutation (44 % of homozygotes). One patient was a mixed heterozygote with the combination C282Y/H63D. 25 patients with a present mutation (48 %) were heterozygotes with one mutated allele. In 33 % of the investigated group (17 patients) with clinical manifestations of HH, none of the known mutations have been demonstrated so far, but increased values of FER and/or ST have been demonstrated.

Results. 61.5 % (32 patients) had an increased ST value, 75 % (39 patients) had an increased FER value. Pathological values of bilirubin were present in 57.69 % (30 patients), pathological values of albumin were present in 34.61 % (18 patients), Pathological values of prothrombin time were present in 5.7 % (3 patients), pathological values of INR were present in 5.7 % (3 patients). Pathological values of ALT were present in 69.2 % (36 patients) and pathological values of AST were present in 73.07 % (38 patients). 9.23 % (10 patients) had hyperglycemia, impaired glucose tolerance was present in 5.76 % (3 patients) and 11.53 % (6 patients) had confirmed diabetes mellitus.

Conclusion. HH is a disease with a different phenotypic manifestation of the disease and the existence of other unknown genetic mutations. Early diagnosis with the use of ST, FER and genetic examination makes it possible to prevent the progression of the disease. The gold standard for the diagnosis of HH is currently a genetic examination, focused on the most frequently occurring mutations in our population. The new classification of HH, which also includes molecularly undefined forms, with a defined clinical phenotype, without molecular characterization, will offer practical use (Tab. 1, Fig. 6, Ref. 97). Text in PDF www.lekarskyobzor.sk.

KEY WORDS: hereditary hemochromatosis, transferrin saturation, ferritin, genetic mutations, genotype, phenotype.

Lek Obz 2022, 71 (11): 443-457

Viera KUPČOVÁ 1, Ladislav TURECKÝ 2

1 III. interná klinika LF UK v Bratislave, prednosta doc. MUDr. V. Mojto, CSc., MPH, MHA
2 Ústav lekárskej chémie, biochémie a klinickej biochémie LF UK v Bratislave, prednosta prof. MUDr. L. Turecký, CSc.

CITE
KUPČOVÁ V., TURECKÝ L.: Hereditary hemochromatosis at a insight of clinician – overview and own experiences. Lek Obz 2022, 71 (11): 443-457