Generalized epimerase deficiency galactosemia.

Galactosemia is caused by inherited deficiencies in one of three enzymes involved in the metabolism of galactose: galactose- 1-phosphate uridyltransferase (GALT), galactokinase (GALK), and uridine diphosphate galactose-4-epimerase (GALE). The rarest and most poorly understood form of galactosemia is due to epimerase deficiency. We are reporting such a rarest form of galactosemia presenting with progressively increasing cholestatic jaundice and failure to thrive at one month of age. After confirmation of decreased epimerase level in RBC hemolysate, the patient was put on galactose restricted diet and vitamins supplementation, which reversed the clinical signs as well as altered liver function. Patient is on regular follow-up and now at 15 months of age he has no marked developmental delay.

Association of fungal sepsis and galactosemia.

Galactosemia is one of the rare inborn errors of metabolism, which if detected early can be treated effectively. Galactosemic infants have a significant increased risk of developing sepsis. E. coli sepsis is a known entity, and also an important cause of early mortality in these children. But fungal sepsis in these patients is rarely reported. Here is a case of 45 day-old child who presented with fungal sepsis, which on investigation turned out to be galactosemia.

Newborn Screening for Classic Galactosemia and Primary Congenital Hypothyroidism in the Nkangala District of the Mpumalanga Province of South Africa

Objectives: The main objective of this work was to establish the newborn incidence of classic galactosemia and congenital hypothyroidism within the Nkangala district of Mpumalanga. In the process a cost effective protocol for newborn screening of both diseases was developed. Study design and setting : Blood spot specimens were collected from over 30of newborn infants in the Nkangala district of Mpumalanga Province in a six month period from June to November 2005. The specimens were subsequently screened for classic galactosemia and hypothyroidism using metabolite quantification assays. GALT (galactose-1-phosphate uridyltransferase) enzyme activity assays were also performed to confirm the reliability of the total galactose assays. Real-time PCR was used to detect commonly occurring mutations in the GALT gene that cause galactosemia. Subjects and outcome measures: Informed consent was obtained from the parents of the newborn infants prior to commencement of screening. Total galactose levels of above 0;9 mg/L and TSH concentrations of above 25;1 mU/L were considered to be indicative of galactosemia and hypothyroidism; respectively. A decrease in the total financial input on the screening protocol was evaluated for significance in cost reduction. Results: The incidence of hypothyroidism was found to be 0.1while none of the newborns presented with classic galactosemia. There was up to 20 reduction in direct input costs of screening when our protocol is applied. Conclusion: Cost effective newborn screening is possible when classic galactosemia and congenital hypothyroidism are screened; simultaneously. Cumulative disease frequency plots confirm the already established fact that hypothyroidism tends to prevail in higher frequencies than classic galactosemia

Congenital intrahepatic porto-systemic venous shunt with galactosemia.

We report a 51-day-old infant with congenital intrahepatic porto-systemic venous shunt associated with galactosemia, who presented with cholestatic jaundice. He was treated with ursodeoxycholic acid, calcium supplements and galactose-free diet. The child was asymptomatic six weeks later.

Galactosemia in Thai patient at Phramongkutklao Hospital: a case report.

Galactosemia is a rare autosomal recessive disorder of galactose metabolism, which occurs as a consequence of a deficiency of one of these three enzymes: galactokinase, galactose-1-phosphate uridyltransferase, and uridine diphosphate galactose-4-epimerase, leading to elevated level of galactose and its metabolites in blood. The presented case was a 2-month-old, Thai female infant with persistent cholestatic jaundice, bilateral posterior subcapsular cataracts, and hepatomegaly. Laboratory investigations showed slightly elevated serum aminotransferase, and increased urinary excretion of galactose, galactitol and galactonate (by urine gas chromatography/mass spectrometry). These findings indicated an error in galactose metabolism. Soy-based formula was introduced to the patient. Clinical and laboratory results were improved after a few months of treatment. Genetic counseling was provided to the family for 25% of recurrence risk. Prenatal diagnosis is not established in Thailand.

Alteración del metabolismo de la galactosa / Galactose metabolism defect

Las alteraciones del metabolismo de la galactosa se producen por el defecto de las enzimas: galactoquinasa (GALK), galactosa-1-fosfato-uridil transferasa (GAL1-PUT) y uridin difosfato galactosa 4' epimerasa (UDPGAL); de ellas la más frecuente es la galactosemia clásica producida por la deficiencia de GAL1PUT. Producto de este defecto se acumula galactosa-1-fosfato, galactosa libre y galactitol en sangre y tejidos, los que producen alteraciones hepáticas, renales y cerebrales. Su herencia es autosómica recesiva y la incidencia estimada a nivel mundial fluctúa entre 1:60.000 a 1:33.000 recién nacidos. Los síntomas y signos más característicos son vómito, diarrea, ictericia, hepatomegalia, cataratas. Si la enfermedad no es tratada oportunamente ocasiona la muerte del niño. El tratamiento consiste en eliminar la lactosa y galactosa de la alimentación, lo que incluye alimentos tales como la leche de todo tipo y sus derivados, la galactosa y alimentos o medicamentos que contenga alguno de estos productos. Se entrega leche de soya y los requerimientos de macro y micro nutrientes se indican según las recomendaciones para edad y sexo. La dieta dura toda la vida ya que la galactosa se transforma en galactitol, existiendo riesgo de producir catarata y daño renal en cualquier momento de la vida. Un buen control se obtiene al mantener el nivel sanguíneo de galactosa-1-fosfato igual o menor a 3.0 mg/dL y urinario de galactitol bajo 0.8 mmol/mol de creatinina.

Cost-benefit analysis of newborn screening for galactosemia in the Philippines.

To determine the incidence of galactosemia (GAL) in the Philippines and to determine whether newborn screening for GAL is cost-beneficial from a societal perspective, cost-benefit analysis was performed. Newborn screening for GAL was done after the 24th hour of life using the Beutler test. Patients screened positive were recalled for confirmatory testing. Using incidence rates obtained from the different participating hospitals of the Philippine Newborn Screening Program (PNSP), the costs for the detection and treatment of GAL were compared to the expected benefits by preventing mental retardation, cataracts and other physical disabilities caused by the disorder that would lead to a loss of productivity for the individual. Sensitivity analyses for incidence and discount rates were also included. Of the 157,186 newborns screened by the PNSP since its inception in 1996, 8 screened positive results. Confirmatory testing of these patients showed that 2 had galactosemia. The incidence of galactosemia in this population therefore, is 1 in 106,006 (95% CI= 1:44,218 - 1:266,796). Projecting the figures to the actual birth rate (1.5M newborns/year), the total costs of the screening program amounted to $1.1M, while the total benefits amounted only to $0.2M, yielding net cost of $0.9M. A cost-benefit analysis of the screening program for galactosemia using the incidence 1 in 106,006 demonstrated that the costs of the program outweigh the benefits. The true incidence of galactosemia in the Philippine population may yield an incidence rate that will result in greater net benefits for the program.

Galactosemia: presentación de un caso clínico, revisión y actualización / Galactosemia: report of a clinical case, review and updating

Presentamos un caso de galactosemia en un recién nacido de pretérmino, treinta y seis semanas de edad gestacional por examen físico, que a partir del tercer día de vida comienza con sintomatología (Ictericia), recibiendo alimentación desde su ingreso con fórmula de inicio y posteriormente al pecho; hasta el 6§ día de vida que debe ser ingresado en UTI en delicado estado clínico. Realizado el diagnóstico tras completar los estudios, con indicación de fórmula libre de lactosa egresa del hospital a los 33 días de vida, continuando su seguimiento por consultorio externo de clínica pediátrica y seguimiento de especialistas en metabolopatías.

Screening for galactosemia: Philippines experience. Newborn Screening Study Group.

Galactosemia is an inborn error of galactose metabolism due to a deficiency of any of the galactokinase, galactose-1-phosphate uridyl transferase (GALT), or epimerase enzymes. The Philippines, with its pilot newborn screening project, has been screening for this disorder for 2 years now. A total of 62,841 babies have been screened using the galactose and galactose-1-phosphate spot test. Confirmatory testing is done by the newborn screening laboratory of the The New Children's Hospital in Westmead, Australia. Two cases of galactosemia: 1 classical galactosemia and 1 galactokinase deficiency have so far been confirmed. Clinical review, problems encountered, and management are described. Long-term outcome of these patients, however, is yet to be determined.

Pregnancy-exaggerated galactosemia and congenital cataracts.

One child in a family and two children in another family had galactosemia and congenital cataract. Two of them had total soft cataracts while in one, cataract was less soft. In addition, they had mild lactosuria. The mothers of the affected children had significant lactosuria and mild galactosuria without cataracts. Fathers did not have galactosuria or lactosuria. Clinically unaffected siblings in one family had mild galactosuria and lactosuria. Pregnancy-exaggerated galactosemia was suspected in these two mothers who gave birth to children with congenital cataract. As an extension of this work, 5001 pregnant women were screened for galactose in urine just before the delivery of babies. Mild galactosuria was present in 54 (1.08%). Three children had congenital cataract and one had changes in posterior pole and cornea. Restriction of lactose by reducing intake of milk and milk products during pregnancy by mothers with galactosuria is recommended to avoid the birth of children with congenital cataract.

Galactosemia como causa de colestasis neonatal prolongada / Prolonged neonatal cholestasis due to galactosemia: a report of four cases

Se presentan cuatro casos de galactosemia clásica cuya manifestación clínica inicial fue colestasis neonatal prolongada, atendidos en el Servicio de Gastroenterología del Instituto Nacional de Pediatría de la Ciudad de México, durante el período comprendido de 1987 a 1990. El diagnóstico definitivo se hizo mediante la medición de la actividad de la enzima galactosa 1-fosfato uridil transferasa en eritrocitos (prueba de Beutler). El manejo de los pacientes consistió básicamente en la restricción de galactosa en la dieta. Dos de los pacientes tuvieron una evolución clínica desfavorable, presentamos uno de ellos secuelas neurológicas importantes y el otro paciente falleció (septicemia)

Padronizaçäo do "spot-test" de Beutler e Baluda para o diagnóstico da galactosemia / Standardisation of Beutler-Baluda spot-test for the galactosemia diagnostic

A galactosemia é uma doença metabólica, causada por um déficit da enzima hexose 1-fosfato uridiltransferase (E.C.2.2.7.12). Seus principais sintomas clínicos säo vömitos e diarréias, que aparecem desde as primeiras ingestöes de leite, alteraçäo hepática e alteraçäo do cristalino com catarata bilateral. Com o objetivo de diagnosticar a galactosemia, foi padronizado um método qualitativo, o "spot-test" de Beutler-Baluda, que permite evidenciar a atividade da enzima, através de uma cascata de reaçöes enzimáticas que leva a formaçäo de NADP reduzido, cuja fluorescência é observada sob luz ultravioleta. A partir desta avaliaçäo 7 pacientes tiveram a confirmaçäo laboratorial do diagnóstico de galactosemia

Diagnóstico bioquímico de 2 niños con galactosemia / Biochemical diagnosis of two children with galactosemia

Se presenta un estudio bioquímico realizado en el Centro Nacional de Genénica Médica a 2 niños remitidos por sospecha clínica de padecer galactosemia. Se realizó la cromatrografía en capa fina para la detección de carbohidratos en orina, y se halló una banda al nivel de galactosa. Posteriormente se procedió a la cuantificación del metabolito en orina y suero, y se detectó éste elevado de ambos fluidos. El diagnóstico bioquímico final consistió en comprobar la deficiencia de la enzima galactosa-1-fosfato uridil transferasa eritrocitaria por el método espectrofotométrico; se comprobó también el carácter de portadores del gen deficiente en los padres de ambos niños

Aminoacidopathies among Iraqi children suspected with inborn errors of metabolism

Biochemical tests confirmed the diagnosis of aminoacidopathy in 48% of total Iraqi children [768] who were clinically suspected with inborn errors of metabolism. Cystinuria, galactosemia and phenylketonuria were the major groups of aminoacidopathy distributed in these children, followed by Hartnup disease, Fanconi syndrome, maple syrup urine disease, occulocerebrorenal disease, homocystinuria. tyrosinosis, mucopolysacharoidosis and histidinaemia, respectively

Nova tecnica de isoeletrofocalizaçao para a hexose 1-fosfato uridiltransferase / A new technique of isoelectrofocusing for the hexose 1-phosphate uridyltransferase

A deficiencia da enzima hexose 1-fosfato uridiltransferase (GALT) provoca a doença, transmitida por caracter autossomico recessivo, conhecida como galactosemia congenita. O padrao isoeletroforetico da GALT foi estudado em eritrocitos (normais e variante Duarte), leucocitos, fibroblastos de pele em cultura, figado e celulas HEPG2 em cultura, usando mini-gel de poliacrilamida, atraves do Phast System Pharmacia. Os extratos enzimaticos foram preparados em uma soluçao de ditiotreitol a 8mM e concentrados apos centrifugaçao no Minicon A25. A separaçao isoeletroforetica foi feita em 2000V,510Vh e 15 graus Centigrado durante 30 minutos. Apos a separaçao foi feita uma coloraçao especifica para a enzima utilizando um corante de tetrazolio. Os resultados obtidos indicam que a heterogeneidade da GALT pode ser facilmente demonstrada por esta tecnica, que e tambem precisa para o diagnostico dos variantes da GALT.