TRANSALDOLASE DEFICIENCY: A NEW CAUSE OF HYDROPS FETALIS AND NEONATAL MULTI-ORGAN DISEASE VASSILI VALAYANNOPOULOS, MD, NANDA M. VERHOEVEN,PHD, KARINE MENTION, MD, GAJJA S. SALOMONS,PHD, DANIÈLE SOMMELET, MD, PHD, MARIE GONZALES, MD, GUY TOUATI, MD, PASCALE DE LONLAY, MD, PHD, CORNELIS JAKOBS,PHD, AND JEAN-MARIE SAUDUBRAY, MD, PHD Transaldolase (TALDO) deficiency is a newly recognized metabolic disease, which has been reported so far in 2 patients presenting with liver failure and cirrhosis. We report a new sibship of 4 infants born to the same consanguineous parents; all presented at birth or in the antenatal period with dysmorphic features, cutis laxa and hypertrichosis, hepatomegaly, spleno- megaly, liver failure, hemolytic anemia, thrombocytopenia, and genitourinary malformations. The clinical courses were variable: the first child died of liver failure at 4 months of age; the second pregnancy was medically terminated at 28 weeks gestation because of hydrops fetalis with oligohydramnios. The third child is doing well at age 7 with liver fibrosis and mild kidney failure. The fourth child is now 21 months old and has hepatosplenomegaly, mild anemia, and thrombocytopenia. Urine assessment of polyols showed elevations of erythritol, arabitol, and ribitol consistent with TALDO deficiency. TALDO activity was undetectable in the patients’ tissues, and mutation in the TALDO1 gene was found in the 4 patients. (J Pediatr 2006;149:713-7) I n recent years, 2 new inborn errors in the pentose phosphate pathway have been described: TALDO deficiency and ribose-5-phosphate isomerase deficiency. 1,2 Both defects lead to altered levels of sugars and polyols in body fluids. TALDO deficiency was diagnosed so far in 2 patients from 2 unrelated Turkish families. 1,3 Both patients presented with liver disease in the neonatal period. One is still alive at 15 years of age and has slowly progressive liver cirrhosis. The other died at age 18 days of intractable liver failure and progressive myocardial hypertrophy. We report an additional sibship of 4 TALDO-deficient patients. Clinical courses in these siblings were very diverse. PATIENTS All 4 consecutive patients were born to the same consanguineous Turkish couple. There were no other healthy children. The parents are first cousins and have no relevant medical histories. Patient 1 Patient 1, a girl, was born after a normal pregnancy despite excessive maternal weight gain (20 kg, with 5 kg gained over the last month). Obstetric ultrasonography (US) performed at 10, 21, and 32 weeks gestation showed a normal fetus and placenta. The infant was growth restricted at delivery at 38 weeks (birth weight = 2510 g, length = 47.5 cm, head circumference = 31 cm). The Apgar scores were normal. The placenta was very large. Clinical examination showed dysmorphic features including hirsutism, cutis laxa, low hair implantation (Figure 1, a), brachycephaly, and antimongoloid slants. The infant had hepatosplenomegaly and elevated liver enzymes (alanine amino- transferase 101 to 118 U/L; aspartate aminotransferase 187 to 217 U/L). Hepatic dysfunction was evident during the first month of life with prothrombin time of 18 seconds, activated partial thromboplastin time  60 seconds (control: 35 sec), low coagulation factors (V  0.4, VII  0.35, I  4 mol/L, low total serum protein (42 g/L) and albumin (24 g/L). Recurrent hypoglycemia with normal plasma insulin levels were easily controlled with continuous feeding. CSF Cerebrospinal fluid EEG Electroencephalography TALDO Transaldolase US Ultrasound GT Gamma glutamyltransferase From the Metabolic Unit, Necker-Enfants Malades Hospital and the Fetopathology Department, Saint Antoine Hospital, Paris, the Department of Pediatric Hematology, Children’s Hospital, Vandoeuvre les Nancy, France, and the Metabolic Laboratory, De- partment of Clinical Chemistry, VU Univer- sity Medical Center, Amsterdam, The Netherlands. Submitted for publication Jan 17, 2006; last revision received May 25, 2006; accepted Aug 4, 2006. Reprint requests: J. M. Saudubray, MD, PhD, Necker-Enfants Malades Hospital, 149, Rue de Sèvres, 75015 Paris, France. E-mail: elisabeth.saudubray@nck.aphp.fr. 0022-3476/$ - see front matter Copyright © 2006 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2006.08.016 713