DOCSLIB.ORG

Biotinidase Deficiency: a Treatable Neurological Inborn Error Of

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Biotinidase Deficiency: a Treatable Neurological Inborn Error Of ,0$-ǯ92/21ǯ0$5&+2019 MEDICINE IN ISRAEL Biotinidase Deficiency: A Treatable Neurological Inborn Error of Metabolism Wisam Hayek MD1*, Yelena Dumin MD PhD2,4*, Galit Tal MD3, Yoav Zehavi MD1, Waheeb Sakran MD1,4 and Ronen Spiegel MD1,4 1Department of Pediatrics B, Emek Medical Center, Afula, Israel 2Clinical Biochemistry Laboratory, Rambam Medical Center, Haifa, Israel 3Metabolic Clinic, Rappaport Children’s Hospital, Rambam Medical Center, Haifa, Israel 4Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel of eye pursuit, and lack of social smiling. Laboratory investi- KEY WORDS: biotin, biotinidase deficiency, seizures, inborn error of gations showed normal levels of serum electrolytes, glucose, metabolism, autosomal recessive calcium, magnesium, ammonia, renal function studies, liver IMAJ 2019; 21: 219–221 transaminases, and arterial blood gases. Serum lactate levels were moderately elevated (4.15 mmol/L, normal value < 2.78 mmol/L). Cerebrospinal fluid (CSF) levels were mildly elevated (2.71 mmol/L, normal value < 2.20 mmol/L) Sepsis workup iotinidase deficiency is a rare inborn error of biotin metab- including blood, urine and CSF cultures were normal, as was B olism with autosomal recessive inheritance. Biotinidase is initial CSF analysis. His brain ultrasound was normal. Initial responsible for the recycling of biotin, an essential co-factor electroencephalogram (EEG) showed an abnormal pattern for the normal function of four human enzymatic carboxy- consistent with burst suppression. lases. Complete deficiency of biotinidase is caused by bi-allelic Therapy with phenobarbital was started, but seizure activ- mutations in the BTD gene encoding this key enzyme and ity continued. Metabolic investigations were obtained, and his results mainly in progressive neurological impairment and urinary organic acid analysis using gas chromatography-mass dermatological manifestations. The clinical symptoms of the spectrometry showed significant excretion of 3-hydroxyisova- disease develop gradually in early infancy and are often non- leric acid (3HIA) as well as slightly increased levels of 3-meth- specific, thus presenting a significant diagnostic challenge for ylcrotonoylglycine, methylcitric and 3-hydroxypropionic acids. the pediatrician since a delay in diagnosis will result in irrevers- A minor elevation of methylmalonic acid was also noticed (23 ible neurological deficits [1]. mmol/mol creatinine, normal value < 12 mmol/mol creatinine We describe a 2-month-old male who presented with new- for age) but was absent on repeated urinary organic acid test onset seizures and hypotonia. Metabolic investigations that [Figure 1A]. Blood-spot acylcarnitine profile measured by included analysis of organic acids and acylcarnitine profile UPLC-MS/MS (ultra-performance liquid chromatography– suggested the diagnosis of biotinidase deficiency, enabling early tandem mass spectrometry) showed elevated levels of C5OH initiation of oral biotin that resulted in complete reversal of the carnitine, and of propionylcarnitine (0.78 mmol/L, normal neurologic symptoms. range 0–0.47), and of methylmalonylcarnitine (3.96 mmol/L, normal range 0–1.15). These findings suggested biotinidase deficiency, and the PATIENT DESCRIPTION analysis of biotinidase enzyme activity in serum revealed The male patient is the first offspring of consanguineous par- almost absent enzyme activity (0.1 nmol/min/ml serum, ents of Arab Muslim descent living in a village in the Nazareth normal range 3–8 nmol/min/ml serum). The diagnosis was region. Pregnancy and delivery were uneventful. further confirmed by genetic analysis of theBTD gene, which He presented initially at the age of 2 months with jerky identified a homozygous frameshift mutation c.393delC movements of both upper and lower limbs and up-rolling eyes that is predicted to result in early truncation of the protein consistent with seizures. On examination he had normal vital (p.Phe131Leufs28*). The infant was started on oral biotin 10 signs, but neurological examination displayed marked head lag, mg daily and within a few days showed remarkable improve- truncal hypotonia, combined with generalized hyper-reflexia ment with cessation of seizures, complete resolution of trun- and clonus. In addition, he exhibited abnormal eye contact, lack cal hypotonia and limb hypertonia, and improvement in eye contact and communication. Repeated tests of organic *The first two authors contributed equally to this study acids showed normalization of all biochemical abnormali- 219 MEDICINE IN ISRAEL ,0$-ǯ92/21ǯ0$5&+2019 Figure 1. Urinary organic acids analysis using gas chromatography-mass spectrometry [A] Increased excretion of 3-hydroxyisovaleric A acid (3HIA) (black arrow) and to a lesser degree 3-methylcrotonoylglycine, methylmalonic acid, methylcitric acid, 3-hydroxypropionic acid TIC: 17070307.D\ data.ms 2.4e+07 2.2e+07 2e+07 1.8e+07 1.6e+07 1.4e+07 1.2e+07 Abundance 1e+07 8000000 6000000 4000000 2000000 8.00 10.0010.00 12.0012.00 14.0014.00 16.0016.00 18.0018.00 20.0020.00 22.0022.00 24.0024.00 26.0026.00 28.0028.00 30.0030.00 32.0032.00 Time [B] 3HIA normalized following the initiation of B oral biotin (black arrow). The arrowhead indicates the urinary phenobarbital excretion. This drug was later discontinued TIC: 17070910.D\ data.ms 2.2e+07 2 e +07 1.8e+07 1.6e+07 1.4e+07 1.2e+07 e Abundance 1 +07 8000000 6000000 4000000 2000000 8.008.00 10.0010.00 12.0012.00 14.0014.00 16.0016.00 18.0018.00 20.0020.00 22.0022.00 24.0024.00 26.0026.00 28.0028.00 30.0030.00 32.0032.00 Time GC-MS: Agilent GC 7890A/ MS 5975, Column: Agilent HP-5MS (30 m, 0.25mmX 0.25μm), Internal standards: 2-Phenylbutyric, Tropic, Margaric ties [Figure 1B]. At age 10 months he demonstrates normal or childhood onset of neurological impairment, including growth and development, no dermatologic abnormalities, and new-onset seizures, evolving hypotonia, ataxia, and develop- normal hearing as confirmed by brainstem evoked response mental deterioration, as well as non-neurological symptoms audiometry such as skin rashes, alopecia, hearing loss, and ophthalmo- logic abnormalities. The disease is easily prevented by early administration of pharmacologic doses of oral biotin, which COMMENT compensates for the unavailable recycled biotin. Moreover, Profound biotinidase deficiency is caused by almost com- neurological symptoms that already appeared can be com- plete deficiency (< 10%) of biotinidase enzyme activity and pletely reversed upon early diagnosis and timely biotin is associated with the most severe presentation of infantile administration. 220 ,0$-ǯ92/21ǯ0$5&+2019 MEDICINE IN ISRAEL Since neurological abnormalities are non-specific and can years. Nevertheless, in agreement with the genetic variability develop gradually without being correctly diagnosed, many of biotinidase deficiency in the Israeli (mainly the non-Jewish) countries include this disorder in their newborn screening population and the successful, simple and available treatment, panel [2]. In Israel, biotinidase deficiency is not included in we strongly recommend reconsidering the incorporation of the national newborn screening, posing a major challenge for this disorder into the current Israeli newborn screening, as was pediatricians in timely diagnosing infants with non-specific done for other treatable disorders [5]. neurological symptoms. Rapid initial metabolic investigations In conclusion, biotinidase deficiency is a rare inborn error of are therefore crucial and should be performed in consultation metabolism with neurological sequelae that can be completely with metabolic experts. The laboratory diagnostic clues include prevented by early recognition and appropriate treatment. This elevated serum and/or CSF lactate, elevated propionylcarnitine case report highlights the importance of timely diagnosis and (C3), hydroxyisovalerylcarnitine (C5OH) on blood-spot acyl- treatment of this disorder. A high index of suspicion is crucial carnitine profile, and increased 3HIA excretion in urine. Upon in any child presenting with unexplained neurological dete- initial suspicion, oral biotin should be initiated and biotinidase rioration. activity assessed. The mutation identified in our patient was previously Correspondence described in two patients from the Nazareth region and in Dr. R. Spiegel Dept. of Pediatrics B, Emek Medical Center, Afula 1834111, Israel another patient from Turkey [3]. Notably, in Nazareth and Phone: (972-4) 649-5576 the surrounding villages, we already know of three different Fax: (972-4) 649-5589 deleterious mutations associated with profound biotinidase email: [email protected], [email protected] deficiency including the current c.393delG, in addition to References c.100G>A [4] and c.1613G>A. Of note, the significantly high 1. Wolf B. Biotinidase deficiency. In: Pagon R, Bird T, Dolan C, eds. GeneReviews. carrier state of the c.100G>A mutation in one specific village University of Washington, Seattle, 2000 (updated9 June 2016) https://www.ncbi. with high inbreeding permitted the inclusion of this mutation nlm.nih.gov/books/NBK1322/. 2. Wolf B. Successful outcomes of older adolescents and adults with profound bio- into the Israeli genetic prenatal couple screening program. tinidase deficiency identified by newborn screening. Genet Med 2017; 19: 396-402. According to national health authorities, the successful imple- 3. Wolf B, Jensen K, Hüner G, Demirkol M, et al. Seventeen novel mutations that mentation of the c.100G>A mutation in this program
Load more

Recommended publications
  • Counsyl Foresight™ Carrier Screen Disease List
    COUNSYL FORESIGHT™ CARRIER SCREEN DISEASE LIST The Counsyl Foresight Carrier Screen focuses on serious, clinically-actionable, and prevalent conditions to ensure you are providing meaningful information to your patients. 11-Beta-Hydroxylase- Bardet-Biedl Syndrome, Congenital Disorder of Galactokinase Deficiency Deficient Congenital Adrenal BBS1-Related (BBS1) Glycosylation, Type Ic (ALG6) (GALK1) Hyperplasia (CYP11B1) Bardet-Biedl Syndrome, Congenital Finnish Nephrosis Galactosemia (GALT ) 21-Hydroxylase-Deficient BBS10-Related (BBS10) (NPHS1) Gamma-Sarcoglycanopathy Congenital Adrenal Bardet-Biedl Syndrome, Costeff Optic Atrophy (SGCG) Hyperplasia (CYP21A2)* BBS12-Related (BBS12) Syndrome (OPA3) Gaucher Disease (GBA)* 6-Pyruvoyl-Tetrahydropterin Bardet-Biedl Syndrome, Cystic Fibrosis GJB2-Related DFNB1 Synthase Deficiency (PTS) BBS2-Related (BBS2) (CFTR) Nonsyndromic Hearing Loss ABCC8-Related Beta-Sarcoglycanopathy and Deafness (including two Cystinosis (CTNS) Hyperinsulinism (ABCC8) (including Limb-Girdle GJB6 deletions) (GJB2) Muscular Dystrophy, Type 2E) D-Bifunctional Protein Adenosine Deaminase GLB1-Related Disorders (SGCB) Deficiency (HSD17B4) Deficiency (ADA) (GLB1) Biotinidase Deficiency (BTD) Delta-Sarcoglycanopathy Adrenoleukodystrophy: GLDC-Related Glycine (SGCD) X-Linked (ABCD1) Bloom Syndrome (BLM) Encephalopathy (GLDC) Alpha Thalassemia (HBA1/ Calpainopathy (CAPN3) Dysferlinopathy (DYSF) Glutaric Acidemia, Type 1 HBA2)* Canavan Disease Dystrophinopathies (including (GCDH) (ASPA) Alpha-Mannosidosis Duchenne/Becker Muscular
    [Show full text]
  • Child Neurology: Hereditary Spastic Paraplegia in Children S.T
    RESIDENT & FELLOW SECTION Child Neurology: Section Editor Hereditary spastic paraplegia in children Mitchell S.V. Elkind, MD, MS S.T. de Bot, MD Because the medical literature on hereditary spastic clinical feature is progressive lower limb spasticity B.P.C. van de paraplegia (HSP) is dominated by descriptions of secondary to pyramidal tract dysfunction. HSP is Warrenburg, MD, adult case series, there is less emphasis on the genetic classified as pure if neurologic signs are limited to the PhD evaluation in suspected pediatric cases of HSP. The lower limbs (although urinary urgency and mild im- H.P.H. Kremer, differential diagnosis of progressive spastic paraplegia pairment of vibration perception in the distal lower MD, PhD strongly depends on the age at onset, as well as the ac- extremities may occur). In contrast, complicated M.A.A.P. Willemsen, companying clinical features, possible abnormalities on forms of HSP display additional neurologic and MRI abnormalities such as ataxia, more significant periph- MD, PhD MRI, and family history. In order to develop a rational eral neuropathy, mental retardation, or a thin corpus diagnostic strategy for pediatric HSP cases, we per- callosum. HSP may be inherited as an autosomal formed a literature search focusing on presenting signs Address correspondence and dominant, autosomal recessive, or X-linked disease. reprint requests to Dr. S.T. de and symptoms, age at onset, and genotype. We present Over 40 loci and nearly 20 genes have already been Bot, Radboud University a case of a young boy with a REEP1 (SPG31) mutation. Nijmegen Medical Centre, identified.1 Autosomal dominant transmission is ob- Department of Neurology, PO served in 70% to 80% of all cases and typically re- Box 9101, 6500 HB, Nijmegen, CASE REPORT A 4-year-old boy presented with 2 the Netherlands progressive walking difficulties from the time he sults in pure HSP.
    [Show full text]
  • TITLE: Biotinidase Deficiency PRESENTER: Anna Scott Slide 1
    TITLE: Biotinidase Deficiency PRESENTER: Anna Scott Slide 1: Hello, my name is Anna Scott. I am a biochemical genetics laboratory director at Seattle Children’s Hospital. Welcome to this Pearl of Laboratory Medicine on “Biotinidase Deficiency.” Slide 2: Lecture Overview For today’s Pearl, I will start with background information about biotinidase including its role in metabolism and clinical features. Then we will discuss different clinical assays that can detect and diagnose the enzyme deficiency. Finally, I will touch on biotinidase as it relates to newborn screening. Slide 3: Background Biotinidase deficiency is an inborn error of metabolism, specifically affecting biotin metabolism. Biotin is also known as vitamin B7. Most free biotin is absorbed through the gut from food. This vitamin is an essential cofactor for four carboxylase enzymes. Biotin metabolism primarily consists of two steps- 1) loading the free biotin into an apocarboxylase to form the active form of the enzyme, called holocarboylases and 2) recycling biocytin back to lysine and free biotin after protein degradation. The enzyme responsible for loading free biotin into new enzymes is holocarboxylase synthetase. Loss of function of this enzyme can cause clinical features similar to biotinidase deficiency, typically with an earlier age of onset and greater severity. Biotinidase deficiency results in failure to recycle biocytin back to free biotin for re-incorporation into a new apoenzyme. Slide 4: Clinical Symptoms and Therapy © 2016 Clinical Chemistry Pearls of Laboratory Medicine Title Classical clinical symptoms associated with biotinidase deficiency include: alopecia, eczema, hearing and/or vision loss, and acidosis. During acute illness, hyperammonemia, seizures, and coma can also manifest.
    [Show full text]
  • Biotinidase Deficiency (Biot) Family Fact Sheet
    BIOTINIDASE DEFICIENCY (BIOT) FAMILY FACT SHEET What is a positive newborn screen? What problems can biotinidase deficiency Newborn screening is done on tiny samples of blood cause? taken from your baby’s heel 24 to 36 hours after birth. The blood is tested for rare, hidden disorders that may Biotinidase deficiency is different for each child. Some affect your baby’s health and development. The children have a mild, partial biotinidase deficiency with newborn screen suggests your baby might have a few health problems, while other children may have disorder called biotinidase deficiency. complete biotinidase deficiency with serious complications. A positive newborn screen does not mean your If biotinidase deficiency is not treated, a child might baby has biotinidase deficiency, but it does mean develop: your baby needs more testing to know for sure. • Muscle weakness • Hearing loss You will be notified by your primary care provider or • Vision (eye) problems the newborn screening program to arrange for • Hair loss additional testing. • Skin rashes What is biotinidase deficiency? • Seizures • Developmental delay Biotinidase deficiency affects an enzyme needed to It is very important to follow the doctor’s instructions free biotin (one of the B vitamins) from the food we for testing and treatment. eat, so it can be used for energy and growth. What is the treatment for biotinidase A person with biotinidase deficiency doesn’t have deficiency? enough enzyme to free biotin from foods so it can be used by the body. Biotinidase deficiency can be treated. Treatment is life- long and includes: Biotinidase deficiency is a genetic disorder that is • Daily biotin vitamin pill(s) or liquid.
    [Show full text]
  • Biotinidase Deficiency
    orphananesthesia Anaesthesia recommendations for patients suffering from Biotinidase deficiency Disease name: Biotinidase deficiency ICD 10: E53.8 Synonyms: Late-Onset Biotin-aesponsive Multiple Carboxylase Deficiency, Late-Onset Multiple Carboxylase Deficiency Disease summary: Biotinidase deficiency (BD), biotin metabolism disorder, was first described in 1982 [1]. It is inherited as an autosomal recessive trait. The incidence of BD in the world is approximately 1/60.000 newborns [1]. Clinical manifestations include neurological abnormalities (seizures, ataxia, hypotonia, developmental delay, hearing loss and vision problems like optic atrophy), dermatological abnormalities (seborrheic dermatitis, alopecia, skin rash, conjunctivitis, candidiasis, hair loss), neuromuscular abnormalities (motor limb weakness, spastic paresis, myelopathy), metabolic abnormalities (ketolactic acidosis, organic aciduria, hyperammonemia) [1-6]. Besides, respiratory problems (apnoea, dyspnoea, tachyponea, laryngeal stridor) and immune deficiency findings (prolonged or recurrent viral/fungal infections) are associated with BD [1,3,4]. Hypotonia and seizures are the most common clinical features [4,7]. Medicine in progress Perhaps new knowledge Every patient is unique Perhaps the diagnostic is wrong Find more information on the disease, its centres of reference and patient organisations on Orphanet: www.orpha.net 1 Disease summary Treatment with 5-10 mg of oral biotin per day results rapidly in clinical and biochemical improvement. However, once vision problems, hearing loss, and developmental delay occur, these problems are usually irreversible even if the child is on biotin therapy [4]. Moreover, BD can lead to coma and death when the child if not treated [8]. In some children, especially after puberty, biotin dose is increased from 10 mg per day to 20 mg per day.
    [Show full text]
  • Newborn Screening FACT SHEET
    Newborn Screening FACT SHEET What is newborn screening? Blood spot screening checks babies for: Arginemia Newborn screening is a set of tests that check babies Argininosuccinate acidemia for serious, rare disorders. Most of these disorders Beta ketothiolase deficiency cannot be seen at birth but can be treated or helped Biopterin cofactor defects (2 types) if found early. The three tests include blood spot, Biotinidase deficiency hearing, and pulse oximetry screening. Carnitine acylcarnitine translocase deficiency Carnitine palmitoyltransferase deficiency (2 types) Carnitine uptake defect Citrullinemia (2 types) Blood spot screening checks for over Congenital adrenal hyperplasia 50 rare but treatable disorders. Early Congenital hypothyroidism Cystic fibrosis detection can help prevent serious health Dienoyl-CoA reductase deficiency problems, disability, and even death. Galactokinase deficiency The box on the right lists the disorders Galactoepimerase deficiency screened for in Minnesota. Galactosemia Glutaric acidemia (2 types) Hearing screening checks for hearing Hemoglobinopathy variants loss in the range where speech is heard. Homocystinuria Hypermethioninemia Identifying hearing loss early helps babies Hyperphenylalaninemia stay on track with speech, language, and Isobutyryl-CoA dehydrogenase deficiency communication skills. Isovaleric acidemia Long-chain hydroxyacyl-CoA dehydrogenase deficiency Pulse oximetry screening checks for a set Malonic acidemia of serious, life-threatening heart defects Maple syrup urine disease known as
    [Show full text]
  • Newborn Screening: Because You Touch the Future Everyday
    Newborn Screening: Because you touch the future everyday January 2007 Purpose of Newborn Screening • Program to screen for congenital and heritable disorders • These disorders may cause severe mental retardation, illness, or death if not treated early in life • If treated, infants may live relatively normal lives • Results in savings in medical costs over time If Untreated, Disorders • Can result in: – Growth problems – Developmental delays – Behavioral/emotional problems – Deafness or blindness – Retardation – Seizures – Coma, sometimes leading to death NBS Screening • Identification is a multi-step process – Blood specimens from infants are analyzed by the laboratory – If a result is abnormal, laboratory staff notifies case management staff – Case management provides follow-up to assist linking families with appropriate providers to • Confirm the test results and • Ensure the infant has the disorder prior to treatment • Ensure the infant receives appropriate treatment Results from Lab • Normal Screen Results • Abnormal results – Results are sent to – Results are reported to submitter when all test Case Management as are final soon as available for that disorder Abnormal Results for each disorder • High Panic Codes – are reported to RN in NBS Case Management – RN will notify MD ASAP. If MD unavailable RN will notify mother • Low Panic Codes – Health Tech will notify MD or facility – Mother notified by letter Abnormal Specimen • Case Management will send: – Lab results for that disorder – ACT sheet specific to that disorder – FACT sheet for families – List of Metabolic Specialists Newborn Screening ACT Sheet [Absent/Reduced biotinidase activity] Biotinidase Deficiency Differential Diagnosis: Biotinidase deficiency; see C5-OH for non-biotinidase associated conditions. Metabolic Description: Biotinidase deficiency results from defective activity of the biotinidase enzyme.
    [Show full text]
  • Genotypic and Phenotypic Correlations of Biotinidase Deficiency in The
    Hsu et al. Orphanet Journal of Rare Diseases (2019) 14:6 https://doi.org/10.1186/s13023-018-0992-2 LETTER TO THE EDITOR Open Access Genotypic and phenotypic correlations of biotinidase deficiency in the Chinese population Rai-Hseng Hsu1,2,3, Yin-Hsiu Chien1,2, Wuh-Liang Hwu1,2, I-Fan Chang2, Hui-Chen Ho4, Shi-Ping Chou2, Tzu-Ming Huang1 and Ni-Chung Lee1,2* Abstract Biotinidase deficiency is an autosomal recessive disorder that affects the endogenous recycling and release of biotin from dietary protein. This disease was thought to be rare in East Asia. In this report, we delineate the phenotype of biotinidase deficiency in our cohort. The genotypes and phenotypes of patients diagnosed with biotinidase deficiency from a medical center were reviewed. The clinical manifestations, laboratory findings, and molecular test results were retrospectively analyzed. A total of 6 patients were evaluated. Three patients (50%) were diagnosed because of a clinical illness, and the other three (50%) were identified by newborn screening. In all patients, the molecular results confirmed the BTD mutation. The three patients with clinical manifestations had an onset of seizure at the age of 2 to 3 months. Two patients had respiratory problems (one with apnea under bilevel positive airway pressure (BiPAP) therapy at night, and the other with laryngomalacia). Hearing loss and eye problems were found in one patient. Interestingly, cutaneous manifestations including skin eczema, alopecia, and recurrent fungal infection were less commonly seen compared to cases in the literature. None of the patients identified by the newborn screening program developed symptoms. Our findings highlight differences in the genotype and phenotype compared with those in Western countries.
    [Show full text]
  • The Myriad Foresight® Carrier Screen
    The Myriad Foresight® Carrier Screen 180 Kimball Way | South San Francisco, CA 94080 www.myriadwomenshealth.com | [email protected] | (888) 268-6795 The Myriad Foresight® Carrier Screen - Disease Reference Book 11-beta-hydroxylase-deficient Congenital Adrenal Hyperplasia ...............................................................................................................................................................................8 6-pyruvoyl-tetrahydropterin Synthase Deficiency....................................................................................................................................................................................................10 ABCC8-related Familial Hyperinsulinism..................................................................................................................................................................................................................12 Adenosine Deaminase Deficiency ............................................................................................................................................................................................................................14 Alpha Thalassemia ....................................................................................................................................................................................................................................................16 Alpha-mannosidosis ..................................................................................................................................................................................................................................................18
    [Show full text]
  • Audit of Organic Acidurias from a Single Centre: Clinical And
    Review Article Clinician’s corner Images in Medicine Experimental Research Case Report Miscellaneous Letter to Editor DOI: 10.7860/JCDR/2017/28793.10632 Original Article Postgraduate Education Audit of Organic Acidurias from Case Series a Single Centre: Clinical and Paediatrics Section Metabolic Profile at Presentation Short Communication with Long Term Outcome SEEMA PAVAMAN SINDGIKAR1, KRITHIKA DAMODAR SHENOY2, NUTAN KAMATH3, RATHIKA SHENOY4 ABSTRACT were confirmed of (IEM), and out of which 15 (39.5%) had OA. Introduction: Organic Acidurias (OA) accounts between 10% Methyl malonic acidemia, multiple carboxylase deficiency and and 40% of confirmed Inborn Errors of Metabolism (IEM) in Propionic Acidemia (PA) constituted the largest proportion. India. With prompt recognition and management, better survival Neurodevelopmental issues (73.3%) and metabolic crisis but adverse neurodevelopmental outcome is reported. (53.3%) were common presenting features. Mean ± SE of ammonia was 639.0±424.1 μg/dl and lactate was 33.6±4.9 Aim: To study the clinical and metabolic presentation, mg/dl. Mean pH, bicarbonate, and anion gap was 7.27±0.07, management with immediate and long term outcome of 14.1±2.3 and 17.9±2.3 respectively. Management was protocol symptomatic children with confirmed OA. based. Death was reported in two cases of PA; other morbidities Materials and Methods: Hospital based study of symptomatic were seen in five. Recurrent crisis (46.7%) complicated the children diagnosed to have OA between 2003 and 2009 and follow up in survivors. Spasticity, extrapyramidal movement the survivors followed up over next five years. Diagnosis was disorder, intellectual subnormality, autism spectrum, attention based on clinical and metabolic presentation and confirmed deficit hyperactivity disorder and sensory neural deafness were by spectrometry analyses of urine and blood.
    [Show full text]
  • Differential Diagnosis of Neonatal and Infantile Erythroderma
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE Acta Dermatovenerol Croat 2007;15(3):178-190 REVIEW Differential Diagnosis of Neonatal and Infantile Erythroderma Lena Kotrulja1, Slobodna Murat-Sušić2, Karmela Husar2 1University Department of Dermatology and Venereology, Sestre milosrdnice University Hospital; 2University Department of Dermatology and Venereology, Zagreb University Hospital Center and School of Medicine, Zagreb, Croatia Corresponding author: SUMMARY Neonatal and infantile erythroderma is a diagnostic and Lena Kotrulja, MD, MS therapeutic challenge. Numerous underlying causes have been reported. Etiologic diagnosis of erythroderma is frequently difficult to University Department of Dermatology establish, and is usually delayed, due to the poor specificity of clinical and Venereology and histopathologic signs. Differential diagnosis of erythroderma is Sestre milosrdnice University Hospital a multi-step procedure that involves clinical assessment, knowledge of any relevant family history and certain laboratory investigations. Vinogradska 29 Immunodeficiency must be inspected in cases of severe erythroderma HR-10000 Zagreb with alopecia, failure to thrive, infectious complications, or evocative Croatia histologic findings. The prognosis is poor with a high mortality rate [email protected] in immunodeficiency disorders and severe chronic diseases such as Netherton’s syndrome. Received: June 14, 2007 KEY WORDS: erythroderma, neonatal, infantile, generalized Accepted: July 11, 2007 exfoliative dermatitis INTRODUCTION Erythroderma is defined as an inflammatory Neonatal and infantile erythroderma is a diag- skin disorder affecting total or near total body sur- nostic and therapeutic challenge. Erythrodermic face with erythema and/or moderate to extensive neonates and infants are frequently misdiagnosed scaling (1). It is a reaction pattern of the skin that with eczema and inappropriate topical steroid can complicate many underlying skin conditions at treatment can lead to Cushing syndrome.
    [Show full text]
  • 06-0718 Index: Benefits
    State of California—Health and Human Services Agency Department of Health Care Services JENNIFER KENT EDMUND G. BROWN JR. DIRECTOR GOVERNOR DATE: July 10, 2018 N.L.: 06-0718 Index: Benefits TO: COUNTY CALIFORNIA CHILDREN’S SERVICES (CCS) ADMINISTRATORS, MEDICAL DIRECTORS, AND MEDICAL CONSULTANTS, INTEGRATED SYSTEMS OF CARE DIVISION (ISCD) STAFF, CCS PROGRAM-APPROVED SPECIAL CARE CENTERS (SCC) SUBJECT: AUTHORIZATION OF DIAGNOSTIC AND TREATMENT SERVICE FOR INFANTS REFERRED BY THE CALIFORNIA NEWBORN SCREENING (NBS) PROGRAM FOR X-LINKED ADRENOLEUKODYSTROPHY (ALD) I. PURPOSE The purpose of this Numbered Letter is to establish CCS policy on the authorization of diagnostic and treatment services for X-linked ALD for individuals with a positive NBS test. II. BACKGROUND X-linked ALD is an inherited peroxisomal disorder in which accumulation of very long chain fatty acids (VCLFA) in the brain, spinal cord and adrenal glands leads to demyelination in the brain and spinal cord, and impaired adrenal corticoid function in the adrenal cortex. The condition results from the mutations of the ABCD1 gene on the X chromosome. The ABCD1 gene codes for the ALD protein, which facilitates transport of VLCFA into peroxisomes. Absence of the protein results in an inability to transport and degrade VLCFA. Over 1,000 mutations associated with ALD have been identified. The incidence is between 1 in 20,000 and 1 in 50,000 births. There are multiple presentations of ALD, including childhood cerebral ALD, adolescent cerebral ALD, ‘Addison’s disease only’ and adrenomyeloneuropathy (AMN). Childhood cerebral ALD most commonly presents in boys between the ages of four to eight years old, with intellectual or behavioral impairments.
    [Show full text]