Asian Biomedicine Vol 9 No 1 February 2015 95 100Department of P - PDF document

Asian Biomedicine Vol. 9 No. 1 February 2015; 95 - 100Department of Pediatrics, Faculty of Medicine, Naresuan University, Phitsanulok 65000, ThailandDepartment of Pathology, Faculty of Medicine, Naresuan University, Phitsanulok 65000, ThailandDepartment of Radiology, Faculty of Medicine, Naresuan University, Phitsanulok 65000, Thailand Classic galactosemia is an inherited disorder of galactose metabolism that is caused by aT). As in other in Thai people is very low. An accumulation of its toxic metabolites leads to acute neonatal toxicity and long-term To present the fourth known published case of classical galactosemia in a Thai infant and review A 4-month-old boy who was born into a Thai family with no history of consanguinity developedpersistent jaundice, hepatosplenomegaly, and lethargy, since introduction to breast-feeding. Urine gas chromatography-mass spectrometry demonstrated a high level of galactose, galactitol, and Long-term complications are diet-independent and inevitable. However early recognition andimmediate withdraw of galactose from the diet can prevent serious morbidity and mortality. Acute neonatal toxicity, classic galactosemia, galactose-1-phosphate uridyl transferase, long-term metabolism, the Leloir pathway. Three key enzymesgalactose-1-phosphate uridyl transferase (GALT),long-term complications. GALT deficiency causes deficiency causesclinically during the neonatal period, after galactoseingestion. Acute neonatal toxicity results in jaundice,hepatosplenomegaly, hepatocellular insufficiency, food, foodThe prevalence of classical galact

osemia, aconsequence of GALT deficiency, varies greatly withdifferent ethnicity. The prevalence of this disease ishigher in people of European origin than in Asians.in Taiwan, and 1:700,000 in Japan [2, 7]. In Thailand,the exact prevalence of classical galactosemia isthe exact prevalence of classical galactosemia isSince 1988, there were to our knowledge only threeThai patients reported as diagnosed with galactosemia[9-12]. In the English language literature, the secondand third cases were available to review.We report a fourth case of classical galactosemiahepatosplenomegaly, and lethargy within a few days Thitima Ngoenmak, Department ofPediatrics, Faculty of medicine, Naresuan University, 96T. Ngoenmak, et al.of Naresuan University.as a first son to nonconsanguineous mother. His familystarted breast-feeding on his third day of life. Twodays later, he developed jaundice, hepatosplenomegaly,and lethargy. He had blood group A, Rh positive andhis mother’s blood group was O, Rh positive. A direct and Enterobacter. He received antibiotics for 14 days. Afterpersistent jaundice, hepatosplenomegaly, and lethargy.confirmed by our laboratory, but the patient waswere 24.57mg% and 12.79 mg% respectively. Plasma110 U/L) were significantlylactose diet and soy milk. Five months later, hisinjury was resolving, but portal fibrosis still presentedheld. Defects on speech and language development Figure 1.A. Hematoxylin and eosin staining ( Masson trichrome staining (with giant cell transformation, intralobular, and portal fibrosis 97Vol. 9 No. 1We report a case of galactos

emia in a 4-month- report a case of galactosemia in a 4-month-1]. Theclinical features and laboratory results of cases ofgalactosemia in Thais are compared as shown inTable 1disease. He developed jaundice on his fifth day of lifeinjury. Although infection subsided and TPN washepatosplenomegaly, and lethargy persisted. The galactonate in the patient’s urine. Figure 3.A. Hematoxylin and eosin staining ( Masson trichrome staining (100). Follow-up liver biopsy, 98T. Ngoenmak, et al. Ngoenmak, et al.we had no genotype study results. The diagnosis ofclassic galactosemia in the present case was basedon clinical features and accessible laboratory results.Elevated blood level of galactose (gal) might besecondary or primary hypergalactosemia. Secondaryhypergalactosemia presents in many abnormalities,including congenital hepatitis, congenital hepaticarteriovenous malformations, patent ductus venosus,tyrosinemia, type 1, citrin deficiency (citrullinemia,type 2), other metabolic-disorders producinghepatocellular disease and Fanconi–Bickel syndrome[3]. Based on the Leloir and alternative pathway asin Figure 4, primary hypergalactosemia disorderresults from an enzymatic defect of galactosemetabolism and is divided into three types, includingGALK deficiency, GALT deficiency, and GALE, and GALEsubsequently changed into galactitol and galactonatethrough the alternative pathway of galactosemetabolism. Subsequently galactose, galactitol, andgalactonate excreted into urine that can be detectedby GCMS. Accumulation of galactitol and galactonatedisease and long-term complications

. Acute neonataltoxicity effects multiple organs, including liver, kidney,,injury, cataract, and ovarian failure [3, 6]. Table 1. The clinical features and laboratory results of Thai galactosemia cases in English literature Second case [11]Third 2 months11 days4 monthsMaleMaleNonconsanguinityNonconsanguinityNonconsanguinityPoor feedingYesYesYesVomitingNoYesYesHepatomegalyYesYesYesGram negative sepsisNoNoYesLethargy and hypotoniaNoYesYesCataractYesNoNoCholestasis jaundiceYesYesYesRising galactose,Rising galactose,Rising galactose,galactitol, andgalactitol, andgalactitol, andgalactonategalactonategalactonateGenetic analysisNoMutation of p.R259WNoLiver biopsy findingNo No Severe hepatocyte lossLong-term complicationsUnavailable 99Vol. 9 No. 1of GALT. The onset of the classical galactosemia isThe onset of the classical galactosemia issymptoms are nonspecific and consist of vomiting,diarrhea, lethargy, hypotonia, and poor feeding withleads to jaundice, hepatocellular insufficiency, andhepatosplenomegaly. Patients with GALT deficiency sepsis.Lethargy and hypotonia indicate brain toxicity. Toxic[6]. Cataracts are an infrequent feature of GALTdeficiency. Merely 14% of patients were affected in[2]. Conversely, cataracts typically appear withinGALK deficiency and GALE deficiency. In onepatients with GALK deficiency, while 5% of patients, while 5% of patientsClinical features of GALE deficiency vary fromisolated hypergalactosemia to severe damage ofselected organs resembling severe classicgalactosemia and cataract, and typically appear withinthe first few months of

life [1, 2]. By contrast withcataract [11]. Liver dysfunction is a predominant1]. Liver dysfunction is a predominantTherefore, many potential causes of neonatal hepatitis,including viral infection and metabolic disorders wereexcluded by investigations.The appropriate treatment for an infant withgalactosemia is to (1) eliminate any lactose-containingformula and breast feeding, and begin a formulasuch as a soy-based formula that contains no lactoseas soon as possible, (2) monitor for signs of sepsis,and (3) monitor for signs of coagulopathy [3].Newborns who are diagnosed early and remain on agalactose restricted diet usually reach adulthood. Inspite of strict dietary adherence, they gradually developa number of long-term complications: delayed languageacquisition, speech defects, cognitive impairment, andlearning problems, cataracts, and hypergonadotrophichypogonadism. Most affected patients have irreversiblechanges liked cataract, cirrhosis, and mental retardation[11, 15]. Growth is generally delayed in most patients, b = pentose phosphate pathway. 1 = hexokinase, 2 = phosphoglucomutase, 3 = UDP-glucose pyrophosphorylase.GALK = galactokinase, GALT = galactose-1-phosphate uridyl transferase, GALE = galactose-6-phosphate 100T. Ngoenmak, et al. Ngoenmak, et al.the few complications, that are produced by reductionthe few complications, that are produced by reductionin growth between infants fed a soy-based formulaor cow’s milk formula [18]. After galactose restrictionand soy milk replacement, hepatocellular injury is lessreduces the severity of tissue injury. Th

is disordershould be diagnosed clearly and urgently, which shouldand other Asian countries, the neonatal screeningNithiwat Vatanavicharn, MD, for the metabolic1.Timson DJ. The structural and molecular biology oftype III galactosemia. IUBMB Life. 2006; 58:83-9.2.Broomfield AA, Brain C, Grunewald S. Galactosaemia3.Berry GT. Galactosemia: when is it a newborn4.Bosch AM. Classical galactosaemia revisited. J5.Bosch AM, Bakker HD, van Gennip AH, vanKempen JV, Wanders RJ, Wijburg FA. Clinical features6.Leslie ND. Insights into the pathogenesis ofgalactosemia. Annu Rev Nutr. 2003; 23:59-80.7.Cheung KL, Tang NL, Hsiao KJ, Law LK, Wong W,8.Wasant P. Organising services for IMD in Thailand:twenty years experience. Ann Acad Med Singapore.9.Wasant P, Matsumoto I, Liammongkolkul S. Detectionchromatography and mass spectrometry. Southeast10.Wasant P, Svasti J, Srisomsap C, Liammongkolkul S.11.Boonyawat B, Kamolsilp M, Phavichitr N.Hospital: a case report. J Med Assoc Thai. 2005; 88:12.Siripunthana S, Sahakitrungruang T, WasharasindhuS, Suphapeetiporn K, Supornsilchai V. A discordant13.Medline A, Medline NM. Galactosemia: earlystructural changes in the liver. Can Med Assoc J.14.Gareth P. Jevon JED. Metabolic Disorders inChildhood. In: Pierre Russo EDR, David A. Piccoli,editor. Pathology of Pediatric Gastrointestinal and15.Ramesh S, Krishnan BR. Galactosemia. Indian Pediatr.16.Waggoner DD, Buist NR, Donnell GN. Long-term17.Ridel KR, Leslie ND, Gilbert DL. An updated review18.Vandenplas Y, De Greef E, Devreker T, Hauser B. Soyinfant formula: is it that bad? Acta Paediatr. 2011;