Publication Details

Title :

Clinical, biochemical, and molecular overview of transaldolase deficiency and evaluation of the endocrine function: update of 34 patients.


J Inherit Metab Dis.

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Williams M1, Valayannopoulos V2,3, Altassan R4, Chung WK5, Heijboer AC6,7, Keng WT8, Lapatto R9, McClean P10, Mulder MF11, Tylki-Szymańska A12, Walenkamp MJE11, Alfadhel M4, Alakeel H4, Salomons GS1, Eyaid W4, Wamelink MMC13.


1 Metabolic Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.

2 Sanofi Genzyme, Cambridge, MA, 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, NY, 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 The Children’s Memorial Health Institute, Department of Pediatric, Nutrition and Metabolic Disease, Warsaw, Poland.

13 Metabolic Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.

Year of Publication:





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.

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.

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.