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Three-quarters of the patients with acute lymphoblastic leukemia (ALL), show numerical or structural chromosomal alterations, which are important factors in leukemogenesis. The use of Multiplex Ligation-dependent Probes Amplification (MLPA) has been mainly limited for searching copy number alterations of genes, suggesting that MLPA could detect numerical alterations in cancer. However, the use of MLPA in pediatrics to analyze subtelomeric sequences for aneuploidy detection has not been considered in previous studies. The aim of this study was to identify aneuploidy for the first time using MLPA and correlate the results with karyotype and DNA-index (DI), from preB ALL patients. Forty-two bone marrow samples were analyzed by cytogenetics and flow cytometry to determine the DI. The chromosomal gains and/or losses were detected by the SALSA MLPA P036 Subtelomere Mix 1 probemix®. The chromosomal number matched in 36 out of 42 samples between MLPA and karyotype (R2=0.7829, p=3.7×10-10), 18/42 between MLPA and DI (R2=0.1556, p=0.023), and 20/42 between karyotype and DI (R2=0.1509, p=0.015). MLPA results correlated with karyotype and DI. The use of MLPA led us to identify a gained marker chromosome. Our results indicate that MLPA could be a useful and fast alternative tool for aneuploidy identification in pediatric leukemia.

Congenital disorder of N-linked deglycosylation (CDDG, MIM 615273) is a very rare autosomal recessive disorder caused by pathogenic variants in the NGLY1 gene. Transient transaminitis is the typical hepatic dysfunction described in these patients, but also included neonatal jaundice, hepatomegaly, splenomegaly, and steatosis. Microscopically, intrahepatic cytoplasmic inclusions and fibrosis are seen. We report a five-year-old male patient who presented a severe episode of acute liver failure (ALF). Exome sequencing identified compound heterozygous pathogenic/likely pathogenic variants in the NGLY1 gene: NM_018297.3:c.1891del, p.(Gln631Serfs*7) in exon 12 and NM_018297.3:c.531dup, p.(Asn178Glnfs*9) in exon 4. Serology for the most frequent viral hepatitis infections, autoimmune panel, and investigations for metabolic or toxic causes were also normal or negative. Hepatic disease resolved favorably after 46 days. Liver function tests and elastography remains normal after a 2-year follow-up. This is the first report of a reversible ALF among patients with NGLY1-CDDG. Although its definitive cause remains unknown, we suggest a direct relation between liver disease and mitochondrial respiratory chain damage in the context of impaired NGLY1 gene function. Further reports are required in order to know the long-term prognosis of ALF in patients with NGLY1-CDDG.