Pyruvate kinase deficiency in 29 Turkish patients with two novel intronic variants.

Pyruvate kinase (PK) is a key enzyme of anaerobic glycolysis. The genetic heterogeneity of PK deficiency (PKD) is high, and over 400 unique variants have been identified. Twenty-nine patients who had been diagnosed as PKD genetically in seven distinct paediatric haematology departments were evaluated. Fifteen of 23 patients (65.2%) had low PK levels. The PK:hexokinase ratio had 100% sensitivity for PKD diagnosis, superior to PK enzyme assay. Two novel intronic variants (c.695-1G>A and c.694+43C>T) have been described. PKD should be suspected in patients with chronic non-spherocytic haemolytic anaemia, even if enzyme levels are falsely normal. Total PKLR gene sequencing is necessary for the characterization of patients with PKD and for genetic counselling.

Coexistence of Bloom Syndrome and Kostmann Disease and a Novel Mutation.

Bloom syndrome (BS) is a rare autosomal recessive inherited disorder. Patients with BS have photosensitivity, telangiectatic facial erythema, and stunted growth. They usually have mild microcephaly, and distinctive facial features such as a narrow, slender face, micrognathism, and a prominent nose. Kostmann disease (KD) is a subgroup of severe congenital neutropenias. The diagnosis of severe congenital neutropenia is based on clinical symptoms, bone marrow findings, and genetic mutation. Here, we report a female patient with a triangular face, nasal prominence, and protruding ears presenting with recurrent infections and severe neutropenia. Molecular genetic testing revealed a compound heterozygous variant in the HCLS-1-associated protein X-1 gene [(c.130_131insA) p.(trp44*), c.430 dup(p.Val144fs)] and a new homozygous variant in Bloom Syndrome RecQ like helicase gene [c.2074+2T>C p.(?)]. She was diagnosed with both BS and KD. To the best of our knowledge, this is the first case of coexisting BS and KD in a patient ever reported.