Monique Williams1, Vassili Valayannopoulos2,3, Ruqaiah Altassan4, Wendy K Chung5, Annemieke C Heijboer6,7, Wei Teik Keng8, Risto Lapatto9, Patricia McClean10, Margot F Mulder11, Anna Tylki-Szymańska12, Marie-Jose E Walenkamp11, Majid Alfadhel4, Hajar Alakeel4, Gajja S Salomons1, Wafaa Eyaid4, Mirjam M C Wamelink1. 1. Metabolic Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands. 2. Sanofi Genzyme, Cambridge, Massachusetts, USA. 3. Reference Center for Inherited Metabolic Disease, Institut IMAGINE, Hopital Universitaire Necker - Enfants Malades, Paris, France. 4. King Abdulaziz Medical City-Riyadh, National Guard Health Affairs, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. 5. Departments of Pediatrics and Medicine, Columbia University, New York, New York, USA. 6. Endocrine Laboratory, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands. 7. Laboratory of Endocrinology, Academic Medical Center, Amsterdam, the Netherlands. 8. Genetic Department, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia. 9. Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. 10. Children's Liver Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK. 11. Department of Pediatrics, VU University Medical Center, Amsterdam, The Netherlands. 12. Department of Pediatric, Nutrition and Metabolic Disease, The Children's Memorial Health Institute, Warsaw, Poland.
Abstract
BACKGROUND: Transaldolase deficiency (TALDO-D) is a rare autosomal recessive inborn error of the pentose phosphate pathway. Since its first description in 2001, several case reports have been published, but there has been no comprehensive overview of phenotype, genotype, and phenotype-genotype correlation. METHODS: We performed a retrospective questionnaire and literature study of clinical, biochemical, and molecular data of 34 patients from 25 families with proven TALDO-D. In some patients, endocrine abnormalities have been found. To further evaluate these abnormalities, we performed biochemical investigations on blood of 14 patients. RESULTS AND CONCLUSIONS: Most patients (n = 22) had an early-onset presentation (prenatally or before 1 month of age); 12 patients had a late-onset presentation (3 months to 9 years). Main presenting symptoms were intrauterine growth restriction, dysmorphic facial features, congenital heart disease, anemia, thrombocytopenia, and hepato(spleno)megaly. An older sib of two affected patients was asymptomatic until the age of 9 years, and only after molecular diagnosis was hepatomegaly noted. In some patients, there was gonadal dysfunction with low levels of testosterone and secondary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) abnormalities later in life. This overview provides information that can be helpful for managing patients and counseling families regarding prognosis. Diagnostic guidelines, possible genotype-phenotype correlations, treatment options, and pathophysiological disease mechanisms are proposed.
BACKGROUND:Transaldolase deficiency (TALDO-D) is a rare autosomal recessive inborn error of the pentose phosphate pathway. Since its first description in 2001, several case reports have been published, but there has been no comprehensive overview of phenotype, genotype, and phenotype-genotype correlation. METHODS: We performed a retrospective questionnaire and literature study of clinical, biochemical, and molecular data of 34 patients from 25 families with proven TALDO-D. In some patients, endocrine abnormalities have been found. To further evaluate these abnormalities, we performed biochemical investigations on blood of 14 patients. RESULTS AND CONCLUSIONS: Most patients (n = 22) had an early-onset presentation (prenatally or before 1 month of age); 12 patients had a late-onset presentation (3 months to 9 years). Main presenting symptoms were intrauterine growth restriction, dysmorphic facial features, congenital heart disease, anemia, thrombocytopenia, and hepato(spleno)megaly. An older sib of two affected patients was asymptomatic until the age of 9 years, and only after molecular diagnosis was hepatomegaly noted. In some patients, there was gonadal dysfunction with low levels of testosterone and secondary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) abnormalities later in life. This overview provides information that can be helpful for managing patients and counseling families regarding prognosis. Diagnostic guidelines, possible genotype-phenotype correlations, treatment options, and pathophysiological disease mechanisms are proposed.
Authors: Emily C Britt; Jorgo Lika; Morgan A Giese; Taylor J Schoen; Gretchen L Seim; Zhengping Huang; Pui Y Lee; Anna Huttenlocher; Jing Fan Journal: Nat Metab Date: 2022-03-28