Fructosuria and recurrent hypoglycemia in a patient with a novel c.1693T > A variant in the 3 ' untranslated region of the aldolase B gene
SAGE OPEN MEDICAL CASE REPORTS
Authors: Catalina Morales-Alvarez, Martha; Laura Ricardo-Silgado, Maria; Nicolas Lemus, Hernan; Gonzalez-Devia, Deyanira; Mendivil, Carlos O.
Abstract
Hereditary fructose intolerance, caused by mutations in the ALDOB gene, is an unusual cause of hypoglycemia. ALDOB encodes the enzyme aldolase B, responsible for the hydrolysis of fructose 1-phosphate in the liver. Here, we report the case of a 33-year-old female patient who consulted due to repetitive episodes of weakness, dizziness and headache after food ingestion. An ambulatory 72-h continuous glucose monitoring revealed multiple short hypoglycemic episodes over the day. After biochemical exclusion of other endocrine causes of hypoglycemia, hereditary fructose intolerance seemed a plausible diagnosis. Repeated measurements of urinary fructose revealed pathologic fructosuria, but genetic testing for the three most common mutations in ALDOB resulted negative. We decided to perform complete Sanger sequencing of the ALDOB gene and encountered a variant consisting of a T>A substitution in position 1963 of the ALDOB transcript (c.1693T>A). This position is located within the 3 ' untranslated region of exon 9, 515 nucleotides downstream the stop codon. After complete withdrawal of dietary fructose and sucrose, the patient presented no new hypoglycemic episodes.
Implementation of a Targeted Next-Generation Sequencing Panel for Constitutional Newborn Screening in High-Risk Neonates
YONSEI MEDICAL JOURNAL
Authors: Lee, Hyunjoo; Lim, Joohee; Shin, Jeong Eun; Eun, Ho Sun; Park, Min Soo; Park, Kook In; Namgung, Ran; Lee, Jin Sung
Abstract
Purpose: Newborn screening (NBS) programs are important for appropriate management of susceptible neonates to prevent serious clinical problems. Neonates admitted to neonatal intensive care units (NICU) are at a potentially high risk of false-positive results, and repetitive NBS after total parenteral nutrition is completely off results in delayed diagnosis. Here, we present the usefulness of a targeted next-generation sequencing (TNGS) panel to complement NBS for early diagnosis in high-risk neonates. Materials and Methods: The TNGS panel covered 198 genes associated with actionable genetic and metabolic diseases that are typically included in NBS programs in Korea using tandem mass spectrometry. The panel was applied to 48 infants admitted to the NICU of Severance Children's Hospital between May 2017 and September 2017. The infants were not selected for suspected metabolic disorders. Results: A total of 13 variants classified as likely pathogenic or pathogenic were detected in 11 (22.9%) neonates, including six genes (DHCR7, PCBD1, GAA, ALDOB, ATP7B, and GBA) associated with metabolic diseases not covered in NBS. One of the 48 infants was diagnosed with an isobutyl-CoA dehydrogenase deficiency, and false positive results of tandem mass screening were confirmed in two infants using the TNGS panel. Conclusion: The implementation of TNGS in conjunction with conventional NBS can allow for better management of and earlier diagnosis in susceptible infants, thus preventing the development of critical conditions in these sick infants.
COA
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