Anemia arregenerativa en el lactante: 2 casos de smdrome de Pearson / A regenerative anemia in infants: 2 cases of Pearson's syndrome

La anemia es frecuente en lactantes, y, aunque su causa, habitualmente, es banal, debe establecerse un diagnóstico etiológico adecuado. Cuando la anemia es arregenerativa, puede deberse a aplasia medular, síndrome mielodisplásico, infiltración medular o déficits de factores hematopoyéticos. Otra posible causa es el síndrome de Pearson, una rara enfermedad mitocondrial que se presenta con anemia asociada a otras citopenias, insuficiencia pancreática, acidosis láctica y gran variabilidad en su presentación clínica condicionada por la heteroplasmia. Es característico encontrar en el aspirado/biopsia de médula ósea vacuolización de los precursores de serie roja y sideroblastos en anillo. El diagnóstico de certeza se establece mediante el estudio genético del ácido desoxirribonucleico mitocondrial con Southern blot (amplificación completa de ácido desoxirribonucleico mitocondrial mediante reacción en cadena de la polimerasa-largo), que obtiene deleción del 70%-80% de 4977 pb (DNAm 8343-13459). No existe tratamiento curativo y las medidas son de soporte. Es frecuente el fallecimiento en los primeros años de vida. Se presentan dos casos de lactantes con síndrome de Pearson.

Anemia is very common in infants. Although its causes are usually not severe and treatable, proper etiologic diagnosis should be established. When anemia is non-regenerative, it can be caused by aplastic anemia, myelodysplastic syndrome, bone marrow infiltration or hematopoietic factors deficiencies. Another possible cause is Pearson's syndrome, a rare mitochondrial disease that causes non-regenerative anemia associated with other cytopenias, pancreatic insufficiency, lactic acidosis and great variability in clinical presentation conditioned by heteroplasmy. It is characteristic to find in bone marrow studies variable vacuolization in erythroblastic progenitors and ring sideroblasts. The diagnosis is established by genetic study of mitochondrial deoxyribonucleic acid performed by Southern blot analysis (complete mitochondrial deoxyribonucleic acid amplification by polymerase chain reaction -long), obtaining 70-80% deletion of 4977 bp (NMD 8343-13459). There is no curative therapy and support treatment is the only available nowadays. Death is frequent in early years of life. Two cases of infants with Pearson syndrome are presented.

The advances and new technologies for the study of mitochondrial diseases / Avanços e novas tecnologias para o estudo das doenças mitocondriais

ABSTRACT Genetic mitochondrial disorders are responsible for the most common inborn errors of metabolism, caused by mutations in either nuclear genes or in mitochondrial DNA. This article presents the prokaryotic origin of the organelle and the relation between nuclear and mitochondrial genomes, as well as current evolutionary models for such mechanisms. It also addresses the structure of mitochondrial genes, their expression pattern, clinical features of gene defects, risk of transmission and current techniques to avoid these events in assisted human reproduction. Finally, it discusses the ethical implications of these possibilities.

RESUMO As doenças genéticas mitocondriais são responsáveis pelos erros inatos do metabolismo mais comuns, causados por mutações tanto em genes nucleares como no DNA mitocondrial. Este artigo apresenta a origem procariótica dessa organela, e a relação entre os genomas nuclear e mitocondrial, bem como modelos evolutivos correntes para esses mecanismos. Também trata da estrutura dos genes mitocondriais, seu padrão de expressão, características clínicas de defeitos genéticos, riscos de transmissão e técnicas atualmente utilizadas para evitar esses eventos em reprodução humana assistida. Finalmente, discute as implicações éticas dessas possibilidades.

Coenzyme Q10 defects may be associated with a deficiency of Q10-independent mitochondrial respiratory chain complexes

BACKGROUND: Coenzyme Q10 (CoQ10 or ubiquinone) deficiency can be due either to mutations in genes involved in CoQ10 biosynthesis pathway, or to mutations in genes unrelated to CoQ10 biosynthesis. CoQ10 defect is the only oxidative phosphorylation disorder that can be clinically improved after oral CoQ10 supplementation. Thus, early diagnosis, first evoked by mitochondrial respiratory chain (MRC) spectrophotometric analysis, then confirmed by direct measurement of CoQ10 levels, is of critical importance to prevent irreversible damage in organs such as the kidney and the central nervous system. It is widely reported that CoQ10 deficient patients present decreased quinone-dependent activities (segments I + III or G3P + III and II + III) while MRC activities of complexes I, II, III, IV and V are normal. We previously suggested that CoQ10 defect may be associated with a deficiency of CoQ10-independent MRC complexes. The aim of this study was to verify this hypothesis in order to improve the diagnosis of this disease. RESULTS: To determine whether CoQ10 defect could be associated with MRC deficiency, we quantified CoQ10 by LC-MSMS in a cohort of 18 patients presenting CoQ10-dependent deficiency associated with MRC defect. We found decreased levels of CoQ10 in eight patients out of 18 (45 %), thus confirming CoQ10 disease. CONCLUSIONS: Our study shows that CoQ10 defect can be associated with MRC deficiency. This could be of major importance in clinical practice for the diagnosis of a disease that can be improved by CoQ10 supplementation.

La mitocondria en la medicina legal y forense / The Mitochondrion in legal and forensic medicine

Las mitocondrias son las organelas intracelulares encargadas de suministrar la mayor parte de la energía necesaria para la actividad celular. Actúan, por lo tanto, como centrales energéticas de la célula y sintetizan ATP a expensas de los sustratos metabólicos. La intoxicación con ácido cianhídrico inhibe estos mecanismos y las alteraciones en el funcionamiento del metabolismo mitocondrial de origen genético o congénito producen innumerables patologías. El conocimiento de las patologías y disfunción de las mitocondrias es de importancia para realizar correctamente el diagnóstico de las causas de muerte. El ADN mitocondrial es de suma importancia en la medicina legal y forense para la identificación de las personas.

Mitochondria are organelles in the cell cytoplasm which supply most of the energy needed for cellular activity. They behave as cell’s power plants and synthesize ATP using metabolic substrates. Intoxication with Hydrocyanic Acid inhibits the synthesis of ATP, generating alterations in the mitochondrial metabolism, either genetic or congenital. The consequences of those alterations are innumerables pathologies. Understanding the pathologies and malfunctions of mitochondria help us to make the right diagnostic about the cause of death. In forensic medicine, mitochondrial DNA is of paramount relevance to people identification.

Multiorgan disorder syndrome (MODS) in an octagenarian suggests mitochondrial disorder / Síndrome mitocondrial no sindrómico con fallas de múltiples sistemas. Presentación de un caso

Non-syndromic, multi-organ mitochondrial disorders (MIDs) are frequently missed if treating physicians are not aware of them. We report a 85 years old Caucasian male, referred for tonic-clonic seizures, presenting with a plethora of abnormalities, including neurodermitis, atopic dermatitis, diabetes, hypertension, renal insufficiency, non-specific colitis, urine bladder lithiasis, bilateral cataracts, atrial fibrillation, diverticulosis, polyneuropathy, vitamin-D-deficiency, renal cysts, left anterior hemi-block, right bundle branch block, pulmonary artery hypertension, and heart failure. Neurological investigations revealed ptosis, quadriparesis, fasciculations, dysarthria, dysdiadochokinesia, tremor, hyperkinesia, ataxia, leukoencephalopathy, and basal ganglia calcification. Based upon this combination of abnormalities a non-syndromic mitochondrial multi-organ disorder syndrome (MIMODS, encephalo-myo-cardiomyopathy) was diagnosed.

Las alteraciones mitocondriales no sindrómicas y mutisistémicas pueden ser pasadas por alto si no se está consciente de su existencia. Presentamos un hombre de 85 años, referido por convulsiones tónico clónicas, que presentaba una plétora de anomalías tales como neurodermatitis, dermatitis atópica, diabetes, hipertensión, insuficiencia renal, colitis no específica, litiasis vesical, cataratas bilaterales, fibrilación auricular, diverticulosis, polineuropatía, deficiencia de vitamina D, quistes renales, hemibloqueo izquierdo anterior y bloqueo de rama derecha, hipertensión pulmonar e insuficiencia cardíaca. El estudio neurológico reveló la presencia de ptosis, cuadriparesia, fasciculaciones, disartria, disdiadocoquinesia, temblor, hiperquinesia, ataxia, leucoencefalopatía y calcificación de ganglios basales. Basados en estos hallazgos, se diagnosticó un síndrome mitocondrial no sindrómico con fallas de múltiples sistemas.

Mitochondrial disorders: Challenges in diagnosis & treatment.

Mitochondrial dysfunctions are known to be responsible for a number of heterogenous clinical presentations with multi-systemic involvement. Impaired oxidative phosphorylation leading to a decrease in cellular energy (ATP) production is the most important cause underlying these disorders. Despite significant progress made in the field of mitochondrial medicine during the last two decades, the molecular mechanisms underlying these disorders are not fully understood. Since the identification of first mitochondrial DNA (mtDNA) mutation in 1988, there has been an exponential rise in the identification of mtDNA and nuclear DNA mutations that are responsible for mitochondrial dysfunction and disease. Genetic complexity together with ever widening clinical spectrum associated with mitochondrial dysfunction poses a major challenge in diagnosis and treatment. Effective therapy has remained elusive till date and is mostly efficient in relieving symptoms. In this review, we discuss the important clinical and genetic features of mitochondrials disorders with special emphasis on diagnosis and treatment.

Enfermedades mitocondriales: diagnóstico diferencial de enfermedad cerebrovascular en adulto joven a propósito de un caso / Mitochondrial diseases: differential diagnosis of cerebrovascular disease in young adults: case report

Introduction: Mitochondrial diseases are a heterogeneous group of disorders characterized by impaired oxidative phosphorylation. Clinical manifestations are varied, depending on the nature of the mutation, phenotype of the mitochondria, degree of competition with normal mitochondrial DNA and affected tissues. The diagnosis is challenging and requires a high clinical suspicion with the corroboration of ragged red fibers on the muscle biopsy. Case report: We present the case of 41 years-old woman, with history of insulin dependent diabetes, bilateral sensorineural deafness, exercise intolerance and muscle weakness, which suffered a pseudovascular event with an increase of lactic acid in blood and cerebrospinal fluid. Brain magnetic resonance imaging showed a right temporo-parietal ischemic lesion. Muscle biopsy confirmed a mitochondrial myopathy. We emphasize the relevance of differential diagnosis of cerebrovascular disease in young adults...

Las enfermedades mitocondriales son un grupo heterogéneo de trastornos en la fosforilación oxidativa, que se expresan según la naturaleza de la mutación, el fenotipo de las mitocondrias, el grado de complementación con el mtDNA normal y tejidos afectados. El diagnóstico se basa en la sospecha clínica y en la corroboración de fibras rojo rasgadas en la biopsia muscular con tricrómico de Gomori, entre otras técnicas. Presentamos un caso de una mujer de 41 años, con antecedentes de diabetes mellitus insulinodependiente, hipoacusia neurosensorial bilateral, intolerancia al ejercicio y debilidad muscular, que sufre un cuadro pseudovascular, con aumento del ácido láctico en sangre y LCR. TC y RM cerebral indican lesión isquémica temporoparietal derecha, y biopsia evidencia miopatía mitocondrial. Destacamos la importancia del diagnóstico diferencial de enfermedad cerebrovascular en adulto joven...

Espectro clínico de pacientes con hallazgos histopatológicos y/o moleculares compatibles con enfermedad mitochondrial / Clinical spectrum of patients with histopathological and/or molecular findings compatible with mitochondrial disease

Objetivo: Describir el espectro clínico de pacientes con diagnóstico definitivo de Enfermedad Mitocondrial, y su correlación con hallazgos bioquímicos, neuroimagenológicos, neuropatológicos, y moleculares. Método: Se revisaron las historias clínicas de pacientes con Enfermedad Mitocondrial evaluados durante el período 1990-2011. Resultados: Se incluyeron 41 pacientes, con una edad media inicial de 3,7 años. Identificamos cuatro grupos:1) Síndromes clásicos (65%): a) MELAS del inglés “Mitochondrial encephalomyopathy, lacticacidosis, and stroke-like episodes”, (diez), b) Síndrome de Leigh (diez) c) Síndrome de Kearns –Sayre (cinco), d) PEO del inglés “Progressive External Ophthalmoplegia” plus (OEP plus) (dos), 2) Miopatía: nueve (21,5%) 3) Encefalomiopatías inespecíficas: cinco (12%). Se realizó biopsia muscular en 37 pacientes. Un 70% evidenció fibras rojo rasgadas, cuatro (10,5%) fibras citocromo oxidasa negativas y ocho (14,7%) incremento de la actividad oxidativa subsarcolemal y en la microscopia electrónica alteraciones del tamaño y número de mitocondrias. En 14 se completaron estudios moleculares: Siete presentaron una mutación puntual A3243G en el ADN mitocondrial (MELAS), un paciente una mutación en el ADN mitocondrial A1351G (Síndrome de Leigh) y un paciente una deleción del ADN mitocondrial (OEP plus). Conclusiones: Se pudo corroborar la existencia en nuestro medio de síndromes asociados a patología mitocondrial tradicionalmente reconocidos. Un grupo de pacientes con encefalomiopatías denominadas inespecíficas presentaron un cuadro clínico variable, hallazgos de laboratorio y de imágenes poco orientadores y fue la sospecha de una enfermedad mitocondrial lo que nos llevó a realizar la biopsia que finalmente fue diagnóstica. Es posible que este grupo sea más numeroso y las limitaciones que implica realizar una biopsia muscular se facilite con los estudios moleculares.

Ataxia crónica en pediatría / [Chronic ataxia in childhood].

Chronic ataxias are an heterogeneous group of disorders that affect the child at different ages. Thus, the congenital forms, generally non progressive are observed from first months of life and are expressed by hypotonia and motor delay long before the ataxia became evident. The cerebral magnetic resonance images (MRI) may be diagnostic in some pictures like Joubert syndrome. The group of progressive hereditary ataxias, usually begin after the infant period. The clinical signs are gait instability and ocular apraxia that can be associated with oculocutaneous telangiectasias (ataxia-telangiesctasia) or with sensory neuropathy (Friedreich ataxia). In this review are briefly described congenital ataxias and in more detailed form the progressive hereditary ataxias autosomal recessive, autosomal dominants and mitochondrials. The importance of genetic study is emphasized, because it is the key to obtain the diagnosis in the majority of these diseases. Although now there are no treatments for the majority of progressive hereditary ataxias, some they have like Refsum disease, vitamine E deficiency, Coenzyme Q10 deficiency and others, thus the diagnosis in these cases is even more important. At present the diagnosis of childhood hereditary ataxia not yet treatable is fundamental to obtain suitable handling, determine a precise outcome and to give to the family an opportune genetic counseling.

Síndrome de Pearson: Reporte de un caso / Pearson syndrome: Case report

Entre las etiologías de anemias en la infancia, las citopatías mitocondriales son poco frecuentes. El síndrome de Pearson se diagnostica principalmente durante etapas iniciales de la vida y es caracterizado por anemia sideroblástica refractaria con vacuolización de células progenitoras en la médula ósea, disfunción del páncreas exocrino y variables alteraciones neurológicas, hepáticas, renales y endocrinas. En el siguiente informe reportamos un nuevo caso de lactante mayor femenino de 14 meses de edad, evaluada de forma multicéntrica con diagnostico clínico y molecular de síndrome de Pearson, con la deleción común de 4.977 pares de bases del ADN mitocondrial. Esta entidad ha sido asociada a diversos fenotipos dentro del amplio espectro clínico de las enfermedades mitocondriales.

Among the etiologies of anemia in the infancy, the mitochondrial cytopathies are infrequent. Pearson syndrome is diagnosed principally during the initial stages of life and it is characterized by refractory sideroblastic anemia with vacuolization of marrow progenitor cells, exocrine pancreatic dysfunction and variable neurologic, hepatic, renal and endocrine failures. We report the case of a 14 month-old girl evaluated by a multicentric study, with clinic and molecular diagnosis of Pearson syndrome, with the 4,977-base pair common deletion of mitochondrial DNA. This entity has been associated to diverse phenotypes within the broad clinical spectrum of mitochondrial disease.

Deficiency in complex IV of mitochondria respiratory chain

Mitochondrial cytopathies are diseases due to a defect of mitochondrial respiratory chain and are characterized by the presence of morphological abnormalities of mitochondria. These diseases may be due to alterations of the mitochondrial or the nuclear genome. The clinical manifestations can be polymorphic as various organs may be involved. We report the case of a 2-year-old boy who has a declined development correlated with a distal renal tubular acidosis. His behavioural and motor development was normal until l2months when a regression of his motor milestones with a pyramidal syndrome was noted. The metabolic investigation and the cranial MRI revealed a Leigh syndrome. The biochemical and immunological studies on biopsied skeletal muscle and cultured skin fibroblasts showed a deficiency in the complex IV respiratory chain [cytochrome c oxidase or COX]

Diabetes mellitus associado à mutação mitocondrial A3243G: freqüência e caracterização clínica / Diabetes mellitus associated with the mitochondrial mutation A3243G: frequency and clinical presentation

Diabetes mitocondrial é freqüentemente associado à mutação mitocondrial A3243G. A prevalência desse subtipo de diabetes na população diabética varia de 0,5 a 3 por cento, dependendo do grupo populacional estudado. OBJETIVO: Examinar a freqüência e o quadro clínico do diabetes associado com a mutação mitocondrial A3243G em pacientes brasileiros com tolerância a glicose alterada. MÉTODOS: A população estudada foi composta por 78 indivíduos portadores de diabetes mellitus tipo 1 (grupo I), 148 diabéticos tipo 2 (grupo II), 15 diabéticos tipo 1 ou tipo 2 portadores de disacusia (grupo III) e 492 indivíduos da comunidade nipo-brasileira com vários graus de intolerância a glicose. O DNA foi extraído de leucócitos do sangue periférico e a mutação A3243G foi determinada através da amplificação por PCR e digestão por Apa 1. Em alguns pacientes, o DNA também foi extraído da mucosa oral e folículo capilar. A mutação A3243G foi identificada em três indivíduos, todos do grupo III, resultando em uma prevalência de 0,4 por cento. Os carreadores da mutação apresentavam diagnóstico do diabetes em idade jovem, índice de massa corpórea normal ou baixo e requerimento de insulina. CONCLUSÃO: Diabetes mitocondrial é um subtipo raro de diabetes em nossa população e deve ser investigado naqueles indivíduos portadores de diabetes e surdez.

Maternal inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial RNA Leu (UUR) at base pair 3243. The prevalence of MIDD in the diabetes population ranges between 0.5-3.0 percent depending on the ethnic background. AIM: To examine the frequency and clinical features of diabetes associated with this mutation in Brazilian patients with glucose intolerance. METHODS: The study population comprised: 78 type 1 diabetic subjects (group I), 148 patients with type 2 diabetes (group II), 15 patients with either type 1 or type 2 diabetes and hearing loss (group III) and 492 Japanese Brazilians with varying degrees of glucose intolerance. DNA was extracted from peripheral blood leucocytes and the A3243G mutation was determined by PCR amplification and Apa 1 digestion. In some individuals DNA was also extracted from buccal mucosa and hair follicles. The 3243 bp mutation was found in three individuals, all from group III, resulting in a prevalence of 0.4 percent. These subjects had an early age of diagnosis of diabetes, low or normal body mass index and requirement of insulin therapy. In conclusion MIDD is rare in our population and should be investigate in patients with diabetes and deafness.

Síndrome psicótica evoluindo com demência como manifestação clinica de deleção do DNA mitocondrial / Psycothic syndrome developing into dementia as a clinical manifestation of mitochondrial DNA deletion

As manifestações das doenças mitocondriais são variadas, acometendo, mais freqüentemente, órgãos com alto metabolismo aeróbico em que são mais abundantes, como, por exemplo, o sistema nervoso. O início dos sintomas em geral é observado na infância havendo relatos de início na idade adulta. Apresentamos caso atípico de doença mitocondrial associada à deleção do DNA mitocondrial em um homem de 39 anos com sintomas psiquiátricos configuraram quadro clínico inicial e somente 12 anos após o início dos sintomas surgiram alterações neurológicas. O diagnóstico da doença mitocondrial foi confirmado por biópsia de músculo sendo documentada deleção do DNA mitocondrial.

The manifestations of mitochondrial disease are variable, affecting more frequently the organs with high aerobic metabolism in which they are more abundant, for example the nervous system. The beginning of symptoms in general is observed at chilhood, but some patients presented on adult age. We present an atypical case associated with mitochondrial DNA deletion. A 39-years-old man with psychiatric symptoms that configured initial clinical picture and only after 12 years of the beginning of symptoms neurological alterations became noticeable. The diagnosis of mitochondrial illness was confirmed by muscle biopsy being documented mitochondrial DNA deletion.

Compromiso multisistémico: ¿y si fuera una enfermedad mitocondrial / Multisystemic involvement: and if it was a mitochondrial disease?

Las mitocondrias como organelos subcelulares claves en la generación de la energía son esenciales para la supervivencia de la vida humana. Sus alteraciones conocidas en la actualidad como enfermedades o citopatías mitocondriales se han constituido en la última década en un área de acelerado desarrollo que involucra a todas las especialidades de la medicina. Focos de estudio de especial interés son la herencia "no tradicional" de estos trastornos con un doble control genético (nuclear y mitocondrial); la expresión variable de estas enfermedades en distintos tejidos (multisistémicas o multitisulares) y el creciente diagnóstico de estos cuadros que parecen ser más frecuentes.

Diagnosis of mitochondrial diseases: clinical and histological study of sixty patients with ragged red fibers.

BACKGROUND: Mitochondrial diseases are caused by mutations in mitochondrial or nuclear genes, or both and most patients do not present with easily recognizable disorders. The characteristic morphologic change in muscle biopsy, ragged-red fibers (RRFs) provides an important clue to the diagnosis. MATERIALS AND METHODS: Demographic data, presenting symptoms, neurological features, and investigative findings in 60 patients with ragged-red fibers (RRFs) on muscle biopsy, seen between January 1990 and December 2002, were analyzed. The authors applied the modified respiratory chain (RC) diagnostic criteria retrospectively to determine the number of cases fulfilling the diagnostic criteria of mitochondrial disease. RESULTS: The most common clinical syndrome associated with RRFs on muscle biopsy was progressive external ophthalmoplegia (PEO) with or without other signs, in 38 (63%) patients. Twenty-six patients (43%) had only external ophthalmoplegia, 5 (8%) patients presented with encephalomyopathy. Specific syndromes were the presenting feature in 8 (13%), Kearns-Sayre syndrome (KSS) in 4 and myoclonus epilepsy with ragged-red fibers (MERRF) in 4. Myopathy was the presenting feature in 5 (8%) and 4 presented with infantile myopathy. Of the 60 patients, 18 (30%) had proximal muscle weakness. Two patients with KSS and one patient with myopathy had complete heart block necessitating pace making. When the modified RC diagnostic criteria were applied, only 26 (43%) patients had one other major criterion in addition to RRFs for the diagnosis of mitochondrial diseases. The remaining 34 (57%) patients with RRFs on muscle biopsy had only some clinical features suggestive of RC disorder but did not fulfill the clinical criteria (of the modified diagnostic criteria) for the diagnosis of mitochondrial diseases. CONCLUSION: In patients with clinical features suggestive of RC disorder, demonstration of RRFs on muscle biopsy helps in confirming the diagnosis of mitochondrial disease in only a subgroup of patients.

Sengers disease: a rare association of hypertrophic cardiomyopathy and congenital cataracts.

Hypertrophic cardiomyopathy is an uncommon childhood cardiac disease and can be primary or secondary. Several systemic diseases are known to be associated with this entity. Senger's disease is a mitochondrial disorder causing congenital cataracts lactic acidosis and skeletal and cardiac myopathy. Diagnosis should be kept in mind when routine neonatal eye screening reveals absent red reflex. The authors report a case of Sengers disease and discuss the underlying pathogenetic mechanisms.

Mitochondrial fatty acid oxidation disorders in Thai infants: a report of 3 cases.

Three infants with documented mitochondrial fatty acid oxidation disorders are described in this report. Case 1. Carnitine/acylcarnitine translocase deficiency. (CACT) (OMIM 212138) A two-day-old male developed sudden cardiac arrest 48 hours postpartum, with a previous history of early death (day 2) in siblings with a history of parental consanguinity; somnolence, inactivity, refusal to suck within 24 h, hepatomegaly, persistent hypoglycemia, hypocalcemia, hyperkalemia and severe metabolic acidosis prior to cardiac arrest. Dried blood spots by tandem mass spectrometry demonstrated 10 x elevation of palmitoylcarnitine, moderate elevation of oleylcarnitine, steroylcarnitine and myristoylcarnitine. Case 2. Medium chain acyl CoA dehydrogenase (MCAD) deficiency. (OMIM 212139) A six-week-old male infant, developed sudden cardiac arrest after contacting a viral illness, resuscitated successfully in the first episode, only to succumb during the second episode, 2 weeks apart. Plasma acylcarnitine via tandem mass spectrometry was reported normal; however, urine organic acids via gas liquid chromatography and mass spectrometry demonstrated characteristic metabolites consistent with MCADD. Case 3. Carnitine deficiency, systemic primary. (CDSP) (OMIM 212140) A one-year-old girl with progressive dyspnea since birth and a history of parental consanguinity. Severe dilated cardiomyopathy with episodes of cardiac decompensations, hepatomegaly, anemia, generalized hypotonia, but no hypoglycemia were demonstrated prior to cardiac arrest. Extremely low carnitine level noted in dried blood spots via tandem mass spectrometry.