Trombosis senovenosa cerebral en un recién nacido con mutación MTHFR C677T tratado con enoxaparina / Cerebral sinovenous thrombosis in a newborn with mutation of MTHFR C677T treated with enoxaparin

Resumen: Introducción: La trombosis senovenosa cerebral neonatal (TSVC), es una patología rara y generalmente grave, de la cual se conoce poco sobre los mecanismos fisiopatológicos responsables y, aunque controvertido, se ha sugerido que la trombofilia genética, puede desempeñar un rol en la patogénesis. Debido a los temores de un sangrado intracraneal el tratamiento anticoagulante con heparina de bajo peso mole cular es controvertido. Objetivo: presentar un recién nacido con una trombosis senovenosa cerebral neonatal, discutir los factores de riesgo trombofílico, y el manejo con heparina de bajo peso molecu lar de la trombosis venosa cerebral. Caso Clínico: Recién nacido de término que debutó a los 8 días de vida con convulsiones clónicas, rechazo al pecho más hipoactividad motora. La neuroimagen con RM mostró una TSVC involucrando múltiples senos venosos, un infarto hemorrágico talámico dere cho y congestión venosa de la sustancia blanca frontal. El estudio de trombofilia puso de relieve una mutación homocigota del gen MTHFR C677T. El tratamiento con heparina de bajo peso molecular se asoció a repermeabilización del seno sagital superior a los 23 días de iniciada la terapia. Conclusio nes: La presentación clínica de la TSVC en el neonato es inespecífica, probablemente en relación con la extensión y gravedad de la lesión y el desarrollo de complicaciones asociadas, como infartos he morrágicos venosos intraparenquimatosos o hemorragia intraventricular. Estas complicaciones son detectables mediante Ecografia o Resonancia Magnética, y deben hacer sospechar una TSVC. En esta experiencia el tratamiento anticoagulante mostró ser seguro y prevenir la extensión de la trombosis.

Abstract: Introduction: Neonatal cerebral sinovenous thrombosis (CSNT) is a rare and generally serious con dition about which there is little knowledge of the responsible pathophysiological mechanisms and, although controversial, it has been suggested that genetic thrombophilia may play a role in its patho genesis. Out of concern for intracranial bleeding, the anticoagulant treatment with low-molecular- weight heparin is controversial. Objective: To present a case of a newborn with neonatal CSNT, to analyze the thrombophilic risk factors, and the management of cerebral venous thrombosis with low-molecular-weight heparin. Clinical Case: Full-term newborn who presented at eight days of life breastfeeding rejection, clonic seizures, and locomotor hypoactivity. The MRI neuroimaging showed a CSNT involving multiple venous sinuses, a right thalamic hemorrhagic infarction, and venous congestion in frontal white matter. Thrombophilia study highlighted a homozygous MTHFR C677T mutation. Treatment with low-molecular-weight heparin was associated with repermeabilization of the superior sagittal sinus after 23 days of starting therapy. Conclusions: The clinical presentation of CSNT in the neonate is nonspecific, probably related to the extent and severity of the injury and the development of associated complications, such as venous hemorrhagic infarctions and intraparenchymal or intraventricular hemorrhage. These complications are detected through ultrasound or MRI, and they should make us suspect a CSNT. In this experience, the anticoagulant treatment proved to be safe and prevents thrombus propagation.

L-methylfolate, a new option in psychiatric treatment, would it be linked to psoriasis relapse? / L-metilfolato, uma nova opção no tratamento psiquiátrico, estaria ligado à recaída de psoríase?

ABSTRACT We report a case of a 61-years-old woman in remission of psoriasis for 20 years. She presented recurrence of psoriasis in the form of plaques few days after taking L-methylfolate 15mg/day. The L-methylfolate was prescribed as an adjuvant for the treatment of depression in a patient with the methylenetetrahydrofolate reductase gene polymorphism (MTHFR).

RESUMO Paciente do sexo feminino, 61 anos, em remissão da psoríase por 20 anos. Apresentou recidiva de psoríase em forma de placas poucos dias após início de tratamento L-metilfolato na dose diária de 15mg. O L-metilfolato foi prescrito como terapêutica coadjuvante para tratamento de depressão em paciente portadora do polimorfismo do gene metilenotetrahidrofolato redutase.

Homocistinuria, reporte de un caso / Homocystinuria, Case Report / Homocistinuria, relato de um caso

Resumen: En este artículo se presenta el caso de una niña de 13 años con historia de cefalea de 2 años de evolución, la cual ha sido estudiada por subluxación del cristalino y fenotipo marfonoide. Para llevar a cabo la investigación se realizó una tomografía cerebral simple que evidenció trombosis de varios senos cerebrales. Posteriormente se hospitalizó a la paciente en la unidad de cuidados intensivos, mientras se anticoagulaba con enoxaparina. Se solicitó un estudio para trombofilia junto con homocisteina en sangre, ante la sospecha de homocistinuria. Luego de confirmarse el diagnóstico se recetó piridoxina y ácido fólico, con lo cual la paciente evolucionó de manera satisfactoria y recuperó las funciones perdidas. El seguimiento de este caso para la investigación permitió encontrar una disminución mayor del 20 % de la homocisteina, sin que sus niveles estuvieran por debajo de 50 µmol/L, hecho que hace a la paciente respondedora parcial a la piridoxina.

Abstract: This article presents the case of a 13-year-old girl with a 2-year history of headache, which has been studied for lens subluxation and Marfanoid phenotype. To carry out this research, a simple brain tomography was performed that showed thrombosis of several sinuses. Subsequently, the patient was hospitalized in the intensive care unit and anticoagulated with enoxaparin. A study was requested for thrombophilia along with homocysteine in blood, on suspicion of homocystinuria. After confirming the diagnosis, pyridoxin and folic acid were prescribed, with which the patient evolved satisfactorily and recovered lost functions. Follow-up on this case for the research allowed us to find a decrease in homocysteine greater than 20 %, without its levels being below 50 µmol/L, which makes the patient partially responsive to pyridoxine.

Resumo: Neste artigo, é apresentado o caso de uma menina de 13 anos, com história de cefaleia de dois anos de evolução, a qual tem sido estudada por subluxação do cristalino e fenótipo marfanoide. Para realizar a pesquisa, foi tomada uma tomografia cerebral simples que evidenciou trombose de vários seios cerebrais. Em seguida, a paciente foi internada na unidade de tratamento intensivo onde recebeu tratamento anticoagulante com enoxaparina. Foi solicitado um estudo para trombofilia junto com homocisteina em sangue, diante da suspeita de homocistinúria. Após o diagnóstico ter sido confirmado, foram receitados piridoxina e ácido fólico, com os quais o estado da paciente evoluiu de maneira satisfatória e ela recuperou as funções perdidas. O seguimento do caso para a pesquisa permitiu verificar uma diminuição maior de 20% da homocisteina, sem que seus niveis estivessem abaixo de 50 µmol/L, fato que torna a paciente apta parcialmente à piridoxina.

Classic homocystinuria and keratoconus: a case report / Homocistinúria clássica e ceratocone: um relato de caso

ABSTRACT Homocystinuria is one of a group of genetic disorders called inborn errors of metabolism. It is characterized by a deficiency of the enzyme that converts homocysteine to cystathionine. Keratoconus is an ophthalmologic condition characterized by thinning of the corneal stroma, which causes the cornea to assume a conical shape. There is little information in the scientific literature about the association between keratoconus and homocystinuria. We believe that a collagen cross-linking defect may be the key to understand the connection between these two conditions. This case report describes a 38-year-old male patient with a diagnosis of classical homocystinuria since age 13. At the age of 16, he received a diagnosis of asymmetrical keratoconus when referred for lensectomy with vitrectomy of his left eye. To the best of our knowledge, this is the first report of a patient with simultaneous homocystinuria and keratoconus.

RESUMO Homocistinúria é parte de um grupo de doenças genéticas chamado erros inatos do metabolismo. É caracterizada por uma deficiência da enzima que converte a homocisteína em cistationina. O ceratocone é uma patologia oftalmológica caracterizada pelo afinamento do estroma corneano, o que faz com que a córnea assuma um formato cônico. Há pouca informação na literatura científica sobre a associação entre ceratocone e homocistinúria. Acreditamos que um defeito no cross-linking do colágeno possa ser a chave para entender a conexão entre estas duas condições. Este relato de caso descreve um paciente masculino de 38 anos com diagnóstico de homocistinúria clássica desde os 13 anos. Aos 16 anos, recebeu o diagnóstico de ceratocone assimétrico quando foi encaminhado para lensectomia com vitrectomia do olho esquerdo. Até onde sabemos, este é o primeiro relato de um paciente com homocistinúria e ceratocone simultâneos.

Report on the External Quality Assessment Scheme for Metabolite Testing in Korea (2016–2017)

External quality assessment (EQA) trials of conventional newborn screening tests for phenylketonuria, galactosemia, congenital adrenal hyperplasia, maple syrup urine disease, homocystinuria, and congenital hypothyroidism, as well as extended newborn screening tests using tandem mass spectrometry, were performed twice in 2016 and 2017. A total of 44 specimens in the form of dried blood spots were distributed in each trial to 16 laboratories. The response rate of these laboratories was 100%. The mean, standard deviation, coefficient of variation, median, and cut-offs were evaluated for each analyte in the newborn screening tests. EQA trials for the analyses of methylmalonic acid, vanillylmandelic acid, catecholamines, metanephrines, organic acids, and amino acids were also performed. A well-designed EQA program and continuous education would improve the performance of metabolite testing.

DNA damage in homocystinuria: 8-oxo-, 8-dihydro-2'-deoxyguanosine levels in cystathionine-ß-synthase deficient patients and the in vitro protective effect of N-acetyl­L­cysteine

Introduction: Homocysteine (Hcy) tissue accumulation occurs in a metabolic disease characterized biochemically by cystathionine ß-synthase (CBS) deficiency and clinically by mental retardation, vascular problems, and skeletal abnormalities. Previous studies indicate the occurrence of DNA damage secondary to hyperhomocysteinemia and it was observed that DNA damage occurs in leukocytes from CBS-deficient patients. This study aimed to investigate whether an oxidative mechanism could be involved in DNA damage previously found and investigated the in vitro effect of N-acety-L-cysteine (NAC) on DNA damage caused by high Hcy levels. Methods: We evaluated a biomarker of oxidative DNA damage in the urine of CBS­deficient patients, as well as the in vitro effect of NAC on DNA damage caused by high levels of Hcy. Moreover, a biomarker of lipid oxidative damage was also measured in urine of CBS deficient patients. Results: There was an increase in parameters of DNA (8-oxo-7,8-dihydro-2'- deoxyguanosine) and lipid (15-F2t-isoprostanes levels) oxidative damage in CBS-deficient patients when compared to controls. In addition, a significant positive correlation was found between 15-F2t-isoprostanes levels and total Hcy concentrations. Besides, an in vitro protective effect of NAC at concentrations of 1 and 5 mM was observed on DNA damage caused by Hcy 50 µM and 200 µM. Additionally, we showed a decrease in sulfhydryl content in plasma from CBS-deficient patients when compared to controls. Discussion: These results demonstrated that DNA damage occurs by an oxidative mechanism in CBS deficiency together with lipid oxidative damage, highlighting the NAC beneficial action upon DNA oxidative process, contributing with a new treatment perspective of the patients affected by classic homocystinuria.

Annual Report on the External Quality Assessment Scheme for Biochemical Genetics in Korea (2015)

Two external quality assessment (EQA) trials of conventional newborn screening tests for phenylketonuria, galactosemia, congenital adrenal hyperplasia, maple syrup urine disease, homocystinuria, and congenital hypothyroidism, as well as newborn screening tests using tandem mass spectrometry, were performed in 2015. A total of 44 specimens in the form of dried blood spots were distributed to 16 laboratories and the response rate of these laboratories was 100%. The mean, standard deviation, coefficient of variation, median, and cut-offs were evaluated for each analyte in the newborn screening tests. Two EQA trials for the analyses of methylmalonic acid, vanillylmandelic acid, catecholamines, metanephrines, organic acids, and amino acids were also performed. A well-designed EQA program and continuous education would improve the performance of biochemical genetics tests.

Homocistinuria, una enfermedad metabólica de diagnóstico tardío en el Perú / Homocystinuria, a metabolic disease of late diagnosis in Peru

La Homocistinuria, es un desorden metabólico autosómico recesivo, cuya forma clásica es causada por deficiencia de cistationina β-sintasa, debido a mutaciones en el gen CBS (Cr 21q22.3). Se describe el caso de un varón de 17 años con hipopigmentación de piel y faneras, retraso psicomotor moderado, hábito marfanoide, miopía severa, subluxación del cristalino bilateral, que además presentó eventos psicóticos y una hemiparesia izquierda secundaria a un infarto lacunar. La determinación de homocisteína en plasma se encontró elevada (>9,9mg/dl), así como niveles altos de nitroprusiato de sodio en orina (4+) que confirmaron el diagnóstico clínico de homocistinuria. La homocistinuria clásica genera múltiples complicaciones a nivel dérmico, oftalmológico, cognitivo, osteoarticular y psiquiátrico; que podrían evitarse con un diagnóstico y tratamiento oportuno a través del tamizaje neonatal, aún no disponible en la mayoría de centros asistenciales en el Perú...

Homocystinuria is an autosomal-recessive metabolic disorder whose classical phenotype is caused by a deficiency of cystathionine β-synthase, due to mutations within the CBS gene (Cr21q22.3). Herein we report a 17 year old man with hypopigmented skin and hair, mental retardation, marfanoid habitus, severe myopia, bilateral lens subluxation, psychotic episodes, and left-sided hemiparesis secondary to a lacunar brain infarction. Laboratory tests showed increased levels of homocysteine (>9.9mg/dl) in plasma and high levels of urinary sodium nitroprusside (4+), consistent with the clinical diagnosis of classical homocystinuria. This systemic disorder includes dermal, ophthalmic, cognitive, osteoarticular and psychiatric alterations, all of which could be potentially prevented with early diagnosis and therapy as part of newborn screening, which is still unavailable in Peru...

Annual Report on the External Quality Assessment Scheme for Biochemical Genetics in Korea (2014)

Two trials of external quality assessment (EQA) of conventional newborn screening tests for phenylketonuria, galactosaemia, congenital adrenal hyperplasia, maple syrup urine disease, homocystinuria, and congenital hypothyroidism, as well as newborn screening tests were performed using tandem mass spectrometry in 2014. A total of 39 specimens in the form of dried blood spots were distributed to 16 laboratories and the response rate of these laboratories was 100%. Screening tests for phenylketonuria and congenital hypothyroidism did not meet the accepted performance criteria in some laboratories. The mean, standard deviation, coefficient of variation, median, and cut-offs were evaluated for each analyte in the newborn screening tests. Two trials of EQA for the analyses of methylmalonic acid, vanillylmandelic acid, catecholamines, metanephrines, organic acids, and amino acids were also performed. A well-designed EQA program and continuous education would improve the performance of biochemical genetic testing.

Relationship of genotypes with clinical phenotypes and outcomes in children with cobalamin C type combined methylmalonic aciduria and homocystinuria / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To analyze mutation types, clinical features, and treatment outcomes of cobalamin C (cblC) type combined methylmalonic aciduria and homocystinuria (MMA-HC) and to investigate the relationship of genotypes with clinical phenotypes and outcomes.</p><p><b>METHODS</b>The clinical data of 16 Chinese children diagnosed with cblC type MMA-HC by gene analysis were retrospectively analyzed. According to the onset age, the patients were classified into early onset (≤1 year) and late onset (>1 year). According to the clinical phenotype, the patients were classified into mild, moderate, and severe groups. All the patients were treated with vitamin B12 (cyanocobalamin) or hydroxocobalamin, betaine, folate, vitamin B6, and L-carnitine.</p><p><b>RESULTS</b>Fifteen patients belonged to the early onset type, including 11 in the severe group and 4 in the moderate group. The remaining one belonged to the late onset type. Seven reported mutations and two novel mutations (c.445_446delTG and c.349G>c) were detected. The c.609G>A and c.658_660delAAG were the most common mutations detected in 13 (81%) out of 16 patients. The genotype caused by compound heterozygous mutations of these two alleles (c.609 G>A/c.658_660delAAG) was the most common in the patients, detected in 4 (25%) out of 16 patients. Patients with this genotype had severe microcephaly and eye diseases and these clinical manifestations were not improved after the treatment. The patient with late-onset cblC type MMA-HC had normal clinical phenotypes after treatment. In the 15 early onset patients, the more severe the clinical phenotype, the worse the treatment outcome.</p><p><b>CONCLUSIONS</b>The cblC type MMA-HC mainly manifests as early onset in China and c.609G >A and c.658_660delAAG are the most common mutations causing this disease. The clinical phenotypes are associated with the outcomes in children with cblC type MMA-HC.</p>

Modified Capsular Tension Ring Scleral Fixation and Toric Intraocular Lens Implantation in a Patient with Homocystinuria

PURPOSE: Purpose: To report a case of modified capsular tension ring scleral fixation and in-the-bag toric intraocular lens (IOL) implantation in a pediatric patient with severe crystalline lens subluxation due to homocystinuria. CASE SUMMARY: A 9-year-old male diagnosed with homocystinuria and crystalline lens subluxation presented with progressive decrease of visual acuity. Uncorrected distant visual acuity (UDVA) and corrected distant visual acuity were 0.03 and 0.6 in the right eye and 0.01 and 0.5 in the left eye, respectively. Slit-lamp examination showed severe crystalline lens subluxation toward the inferiomedial side in both eyes. Corneal astigmatism in the right eye and left eye was 2.75 diopters (D) and 3.00 D, respectively based on keratometry. A combination of subluxated crystalline lens aspiration, scleral-fixated modified capsular tension ring insertion and in-the-bag toric IOL implantation were performed in both eyes. After continuous curvilinear capsulorhexis, nucleus and cortex of the crystalline lens were removed by irrigation and aspiration. A modified capsular tension ring with 2 fixation hooks (Model 2-L) was inserted into the capsular bag and fixed at the scleral wall. Next, toric IOL was inserted into the capsular bag. UDVA was 0.8 in the right eye and 0.9 in the left eye and 3 months postoperatively, the IOL rotation was less than 3 degrees from intended axis in both eyes. CONCLUSIONS: In a patient with severe congenital crystalline lens subluxation and moderate to severe corneal astigmatism, scleral fixation of modified capsular tension ring and in-the-bag toric IOL implantation is a possible surgical option.

Methylenetetrahydrofolate reductase deficiency-induced schizophrenia in a school-age boy / 中国当代儿科杂志

Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder. It is known that MTHFR deficiency may result in hyperhomocysteinemia, but MTHFR deficiency-induced schizophrenia has been rarely reported. Here we present the clinical course, biochemical and genetic characteristics of schizophrenia resulted from MTHFR deficiency in a school-age boy. He was 13 years old. He was admitted with a two-year history of fear, auditory hallucination, learning difficulty, sleeping problems, irascibility, drowsing and giggling. At admission, he had significantly elevated plasma and urine levels of total homocysteine, significantly decreased levels of folate in serum and cerebrospinal fluid, and a normal blood concentration of methionine. Further DNA sequencing analysis showed 665C>T homozygous mutations in the MTHFR gene. The patient was diagnosed with MTHFR deficiency-associated schizophrenia and treatment with calcium folinate, vitamin B12, vitamin B6, and betaine was initiated. After the treatment for 1 week, his plasma and urine levels of homocysteine were decreased to a normal range and the clinical symptoms were significantly improved. After 3 months of treatment, the patient returned to school. He is now living with normal school life. In summary, children with late-onset MTHFR deficiency and secondary cerebral folate deficiency may lead to schizophrenia. This rare condition can be early diagnosed through analyses of blood and urine total homocysteine, amino acids in blood and folate in blood and cerebral fluid and successfully treated with folinic acid, vitamin B6, vitamin B12 and betaine.

Annual Report on External Quality Assessment of Biochemical Genetics in Korea (2013) / 임상검사와정도관리

Two trials of external quality assessment (EQA) of conventional newborn screening tests for phenylketonuria, galactosaemia, congenital adrenal hyperplasia, maple syrup urine disease, homocystinuria, and congenital hypothyroidism, as well as of newborn screening tests using tandem mass spectrometry were performed in 2013. A total of 32 specimens in the form of dried blood spots were distributed to 16 laboratories and the response rate of these laboratories was 100%. Total T4, free T4, 17-hydroxyprogesterone, leucine, isoleucine, galactose, methionine, alanine, C8/C2, C8/C10, and C5-OH did not meet the accepted performance criteria. The mean, standard deviation, coefficient of variation, median, and cut-offs were evaluated for each analyte in the newborn screening tests. Two trials of EQA for the analyses of methylmalonic acid, vanillylmandelic acid, very long fatty acids, organic acids, and amino acids were also performed. A well-designed EQA program and continuous education would improve the performance of biochemical genetic tests.

Outcomes of patients with combined methylmalonic acidemia and homocystinuria after treatment / 中华儿科杂志

<p><b>OBJECTIVE</b>Combined methylmalonic acidemia with homocystinuria is a common form of methylmalonic acidemia in China. Patients with this disease can progress to death without timely and effective treatment. This study aimed to analyze the treatment outcomes of patients with combined methylmalonic acidemia and homocystinuria.</p><p><b>METHOD</b>From September 2004 to April 2012, 58 patients with combined methylmalonic acidemia and homocystinuria (34 males and 24 females) were diagnosed and treated in our hospital. Fifty cases were from clinical patients including 42 early-onset cases and 8 late-onset cases. Their age when they were diagnosed ranged from 18 days to 30.8 years. The other 8 cases were from newborn screening. All the patients were treated with vitamin B12, betaine, folic acid, vitamin B6, and L-carnitine. The physical and neuropsychological development, general laboratory tests, the levels of amino acids, acylcarnitines, and homocysteine in blood, and organic acids in urine were followed up.</p><p><b>RESULT</b>The follow-up period ranged from 1 month to 7.1 years. Three cases died (all were early-onset cases). In the other patients after treatment, the symptoms such as recurrent vomiting, seizures, lethargy, and poor feeding disappeared, muscle strength and muscle tension were improved, and general biochemical abnormalities such as anemia and metabolic acidosis were corrected. Among the surviving 55 cases, 49 had neurological impairments such as developmental delay and mental retardation. The median levels of blood propionylcarnitine and its ratio with acetylcarnitine, serum homocysteine, and urine methylmalonic acid were significantly decreased (P < 0.01), from 7.73 µmol/L (ranged from 1.5 to 18.61 µmol/L), 0.74 (ranged from 0.29 to 2.06), 97.3 µmol/L (ranged from 25.1 to 250 µmol/L) and 168.55 (ranged from 3.66 to 1032.82) before treatment to 2.74 µmol/L (ranged from 0.47 to 12.09 µmol/L), 0.16 (ranged from 0.03 to 0.62), 43.8 µmol/L (ranged from 17 to 97.8 µmol/L) and 6.81 (ranged from 0 to 95.43) after treatment, respectively.</p><p><b>CONCLUSION</b>Patients with combined methylmalonic acidemia and homocystinuria respond to a combined treatment consisting of supplementation of hydroxycobalamin, betaine, folic acid, vitamin B6 and L-carnitine with clinical and biochemical improvement. But the long-term outcomes are unsatisfactory, with neurological sequelae in most patients.</p>

Consumo de fumonisinas y daños a la salud humana / Fumonisin intake and human health

Las fumonisinas son una familia de micotoxinas que contaminan al maíz, alteran el metabolismo de los esfingolípidos y del folato, se asocian con defectos del tubo neural y están catalogadas por la Agencia Internacional de Investigación en Cáncer (IARC por sus siglas en inglés) como posibles carcinógenos humanos. Debido a que en México los derivados de maíz constituyen una parte importante de la dieta y existe alta prevalencia de población genéticamente susceptible a la deficiencia de folato, en este ensayo se presentan las evidencias mundiales y nacionales de la exposición a fumonisinas y la relevancia que para México representa la evaluación de esta exposición.

Fumonisins are mycotoxins that contaminate maize, disrupt the folate and sphingolipid metabolism, are associated with neural tube defects, and are considered by the International Agency for Research on Cancer (IARC) as possible human carcinogens. Since maize-based foods are significant components of the Mexican diet and there is a high prevalence of genetic susceptibility for folate deficiency among Mexicans, this essay presents international and national evidence of fumonisin exposure and the relevance that such exposure represents for Mexico.

Spectrum of patients with hypermethioninemia based on neonatal screening tests over 14 years / 소아과

PURPOSE: The neonatal screening test for homocystinuria primarily measures methionine by using a dried blood specimen. We investigated the incidence and clinical manifestations of homocystinuria, isolated hypermethioninemia, and transient hypermethioninemia among patients with hypermethioninemia on a neonatal screening test. METHODS: We performed a retrospective study of 58 patients transferred to Shoonchunhyang Hospital because of hypermethioninemia on a neonatal screening test between January 1996 and August 2009. We analyzed the level of amino acid from plasma and urine, as well as blood homocysteine. RESULTS: Almost half of the 58 patients were identified as normal. Whereas only 3 (5.1%) patients were identified as having homocystinuria, about 20.7% (12 cases) of the patients had isolated hypermethioninemia. The ages of these two groups at initial detection of hypermethioninemia on plasma amino acid analysis were 50.0+/-22.5 days and 34.9+/-13.5 days, respectively. Both groups were put on diets, and they showed a normal developmental course as a result of early diagnosis and treatment. CONCLUSION: Hypermethioninemia without homocystinuria, referred to as isolated hypermethioninemia, was also detected. Thus, the impact of hypermethioninemia on a neonatal screening test should be carefully evaluated through analysis of amino acid levels from blood and urine, and we need to detect and treat an early stage of isolated hypermethioninemia as well as homocystinuria.

Homocystinuria due to cystathionine beta synthase deficiency.

A two year-old male child presented with cutis marmorata congenita universalis, brittle hair, mild mental retardation, and finger spasms. Biochemical findings include increased levels of homocysteine in the blood-106.62 micromol/L (normal levels: 5.90-16 micromol/L). Biochemical tests such as the silver nitroprusside and nitroprusside tests were positive suggesting homocystinuria. The patient was treated with oral pyridoxine therapy for three months. The child responded well to this therapy and the muscle spasms as well as skin manifestations such as cutis marmorata subsided. The treatment is being continued; the case is reported here because of its rarity. Homocysteinuria arising due to cystathionine beta-synthase (CBS) deficiency is an autosomal recessive disorder of methionine metabolism that produces increased levels of urinary homocysteine and methionine It manifests itself in vascular, central nervous system, cutaneous, and connective tissue disturbances and phenotypically resembles Marfan's syndrome. Skin manifestations include malar flush, thin hair, and cutis reticulata / marmorata.

A Cost-Benefit Analysis of Neonatal Screening Tests for Maple Syrup Urine Disease, Homocystinuria, Galactosemia, and Congenital Adrenal Hyperplasia

PURPOSE: Neonatal screening tests are increasingly being used forearly diagnosis of inborn errors of metabolism (IEM) in the hope of avoiding the severe developmental delay, acute illness, and death that may result from these diseases. In this study, a cost-benefit analysis was performed on the neonatal screening of maple syrup urine disease, homocystinuria, galactosemia, and congenital adrenal hyperplasia in Korea. MATERIALS AND METHODS: This study included 1,259,220 Korean newborns born between January 2005 to December 2007, who were screened for maple syrup urine disease, homocystinuria, galactosemia, and congenital adrenal hyperplasia. We calculated and compared the total costs in cases where these four screening tests were implemented, and those where they were not. RESULTS: There were no benefits to screening for maple syrup urine disease or homocystinuria due to their low prevalence for these two tests, the costs exceeded the benefits at benefit:cost ratios of 0.5:1 and 0.6:1, respectively. In contrast, benefits far exceed costs at a ratio of 4.1:1 for galactosemia and 2.9:1 for congenital adrenal hyperplasia. The average benefit:cost ratio for all four tests was 2.0:1. CONCLUSION: Neonatal screening tests for maple syrup urine disease, homocystinuria, galactosemia, and congenital adrenal hyperplasia are financially viable.