RESUMEN

PURPOSE: Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency (LCHADD) is a rare fatty acid oxidation disorder characterized by recurrent episodes of metabolic decompensation and rhabdomyolysis, as well as retinopathy, peripheral neuropathy, and cardiac involvement, such as infantile dilated cardiomyopathy. Because LCHADD patients are surviving longer, we sought to characterize LCHADD-associated major cardiac involvement in adolescence and young adulthood. METHODS: A retrospective cohort of 16 adolescent and young adult participants with LCHADD was reviewed for cardiac phenotype. RESULTS: Major cardiac involvement occurred in 9 of 16 participants, including sudden death, out-of-hospital cardiac arrest, acute cardiac decompensations with heart failure and/or in-hospital cardiac arrest, end-stage dilated cardiomyopathy, and moderate restrictive cardiomyopathy. Sudden cardiac arrest was more common in males and those with a history of infant cardiomyopathy. CONCLUSION: The cardiac manifestations of LCHADD in adolescence and early adulthood are complex and distinct from the phenotype seen in infancy. Life-threatening arrhythmia occurs at substantial rates in LCHADD, often in the absence of metabolic decompensation or rhabdomyolysis. The potential risk factors identified here-male sex and history of infant cardiomyopathy-may hint at strategies for risk stratification and possibly the prevention of these events.

Asunto(s)

Errores Innatos del Metabolismo Lipídico , Fenotipo , Humanos , Masculino , Adolescente , Femenino , Adulto Joven , Adulto , Errores Innatos del Metabolismo Lipídico/genética , Errores Innatos del Metabolismo Lipídico/patología , Estudios Retrospectivos , Rabdomiólisis/genética , Rabdomiólisis/patología , Rabdomiólisis/enzimología , 3-Hidroxiacil-CoA Deshidrogenasa de Cadena Larga/genética , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/patología , Cardiomiopatías/genética , Cardiomiopatías/patología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patología

RESUMEN

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiencies are rare fatal disorders of fatty acid ß-oxidation with no apparent genotype-phenotype correlation. The measurement of acylcarnitines by MS/MS is a current diagnostic workup in these disorders. Nevertheless, false-positive and false-negative results have been reported, highlighting a necessity for more sensitive and specific biomarkers. This study included 54 patients with LCHAD/MTP deficiency that has been confirmed by biochemical and molecular methods. The analysis of acylcarnitines in dried blood spots was performed using ESI-MS/MS. The established "HADHA ratio" = (C16OH + C18OH + C18:1OH)/C0 was significantly elevated in all 54 affected individuals in comparison to the control group. Apart from 54 LCHAD deficiency patients, the "HADHA ratio" was calculated in 19 patients with very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. As VLCAD-deficient patients did not show increased "HADHA ratio", the results emphasized the high specificity of this new ratio. Therefore, the "HADHA ratio" was shown to be instrumental in improving the overall performance of MS/MS-based analysis of acylcarnitine levels in the diagnostics of LCHAD/MTP deficiencies. The ratio was demonstrated to increase the sensitivity and specificity of this method and reduce the chances of false-negative results.

RESUMEN

Early-onset long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency is a fatty acid ß-oxidation disorder with a poor prognosis. Triheptanoin, an anaplerotic oil with odd-chain fatty acids can improve the disease course. The female patient presented here was diagnosed at the age of 4 months, and treatment was started as fat restriction, frequent feeding, and standard medium-chain triglyceride supplementation. In follow-up, she had frequent rhabdomyolysis episodes (∼8 per year). At the age of six, she had 13 episodes in 6 months, and triheptanoin was started as part of a compassionate use program. Following unrelated hospital stays due to multisystem inflammatory syndrome in children and a bloodstream infection, she had only 3 rhabdomyolysis episodes, and hospitalized days decreased from 73 to 11 during her first year with triheptanoin. Triheptanoin drastically decreased the frequency and severity of rhabdomyolysis, but progression of retinopathy was not altered.

Asunto(s)

Errores Innatos del Metabolismo Lipídico , Rabdomiólisis , Humanos , Niño , Femenino , Lactante , 3-Hidroxiacil-CoA Deshidrogenasas/metabolismo , Oxidación-Reducción , Triglicéridos/uso terapéutico , Errores Innatos del Metabolismo Lipídico/complicaciones , Errores Innatos del Metabolismo Lipídico/diagnóstico , Errores Innatos del Metabolismo Lipídico/tratamiento farmacológico , Rabdomiólisis/tratamiento farmacológico , Coenzima A

RESUMEN

Purpose: To report the clinical utility of optical coherence tomography angiography (OCTA) for demonstrating choroidal neovascularization (CNV) associated with Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHADD) retinopathy. Methods: Thirty-three participants with LCHADD (age 7-36 years; median 17) were imaged with OCTA and the Center for Ophthalmic Optics & Lasers Angiography Reading Toolkit (COOL-ART) software was implemented to process OCTA scans. Results: Seven participants (21 %; age 17-36 years; median 25) with LCHADD retinopathy demonstrated evidence of CNV by retinal examination or presence of CNV within outer retinal tissue on OCTA scans covering 3 × 3 and/or 6 × 6-mm. These sub-clinical CNVs are adjacent to hyperpigmented areas in the posterior pole. CNV presented at stage 2 or later of LCHADD retinopathy prior to the disappearance of RPE pigment in the macula. Conclusion: OCTA can be applied as a non-invasive method to evaluate the retinal and choroidal microvasculature. OCTA can reveal CNV in LCHADD even when the clinical exam is inconclusive. These data suggest that the incidence of CNV is greater than expected and can occur even in the early stages of LCHADD retinopathy.

RESUMEN

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a rare mitochondrial defect of ß-oxidation of long-chain fatty acids. Patients may present with muscle pain, hypotonia, peripheral neuropathy, cardiomyopathy, recurrent rhabdomyolysis and sudden death. Dietary management of LCHADD aims at preventing prolonged fasting and decreasing energy production from long-chain fatty acids compensated by an increase in medium-chain triglyceride fat. Herein, we present medical and dietetic management of a successful pregnancy in a LCHADD female patient and the delivery of a healthy baby boy.

RESUMEN

Axonal peripheral neuropathy is a common complication of mitochondrial trifunctional protein (MTP) deficiency and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency that is usually considered progressive. Current treatment strategies are not able to fully prevent neuropathic symptoms in the majority of patients. We herein report three sisters with genetically proven MTP deficiency who were untreated until adolescence, when electrophysiological studies first revealed isolated axonal sensory neuropathy. Apart from mild exercise intolerance and missing deep tendon reflexes of the lower extremities, all three girls were clinically asymptomatic. A fat-reduced and fat-modified diet together with a reduction of the nocturnal fasting time resulted in complete normalisation of the electrophysiological studies after 1 year of dietary treatment. Our findings suggest that neuropathy might be responsive to dietary interventions in MTP patients at a very early stage of disease.

RESUMEN

This is the first report of the concurrent development of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and Crigler-Najjar syndrome type 1 (CNs1) inherited via uniparental disomy of chromosome 2, which are both autosomal recessive pathologies. Through an expanded newborn metabolic panel, a male infant was identified as having an acylcarnitine pattern typical for LCHADD, later confirmed to be caused by a well-characterized pathogenic variant in the HADHA gene located at 2p23. Prolonged non-hematologic jaundice requiring repetitive phototherapy prompted further genetic analysis, leading to the identification of another genetic abnormality consistent with CNs1, which was caused by a novel pathogenic variant in the UGT1A1 gene located at 2q37. The two identified point mutations in chromosome 2 were homozygous and present on separate arms, which indicated potential uniparental disomy. Microarray analysis of the genetic material from the patient and his parents confirmed paternal isodisomy of chromosome 2. Further studies are needed to identify other possible pathogenic variants located on the same defective chromosome, evaluate the combined effect of the two metabolic abnormalities, and plan the best possible treatment and care.

Asunto(s)

Síndrome de Crigler-Najjar , Cardiomiopatías , Cromosomas Humanos Par 2/genética , Síndrome de Crigler-Najjar/genética , Humanos , Lactante , Recién Nacido , Errores Innatos del Metabolismo Lipídico , Masculino , Miopatías Mitocondriales , Proteína Trifuncional Mitocondrial/deficiencia , Enfermedades del Sistema Nervioso , Rabdomiólisis , Disomía Uniparental/genética

RESUMEN

Peripheral neuropathy is a known irreversible long-term complication of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and mitochondrial trifunctional protein deficiency (MTPD), two inherited disorders of mitochondrial long-chain fatty acid oxidation. The underlying pathophysiology of neuropathy is still not fully understood. We report electrophysiological studies and neurological findings in a series of 8 LCHAD-deficient and 11 MTP-deficient patients. The median age at time of the study was 8.0 years (0.5-25 years). The overall prevalence of neuropathy was 58% with neuropathic symptoms being slightly more common in MTPD compared to LCHADD (70% vs 50%, respectively). Onset of neuropathy was significantly earlier in MTPD patients compared to LCHADD patients (median age at onset 4.7 vs 15.3 years, respectively, P = .047). In four patients, isolated peripheral neuropathy was the first and only presenting symptom, and in all four the diagnosis was missed by newborn screening. About half of the patients (45.5%) had a sensorimotor neuropathy, while 27.3% showed a pure motor form and another 27.3% an isolated sensory form. Despite early diagnosis by newborn screening and early initiation of therapy, peripheral neuropathy cannot be prevented in all patients with LCHADD/MTPD and has severe impact on the life of affected patients. Electrophysiology classifies LCHADD/MTPD neuropathy as axonal with secondary demyelination. A novel observation is that in patients with acute, fulminant onset of neuropathy, symptoms can be partly reversible. Further studies are needed to elucidate the underlying pathophysiology of axonal damage and possible therapeutic targets.

Asunto(s)

Cardiomiopatías/complicaciones , Errores Innatos del Metabolismo Lipídico/complicaciones , Miopatías Mitocondriales/complicaciones , Proteína Trifuncional Mitocondrial/deficiencia , Enfermedades del Sistema Nervioso/complicaciones , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/etiología , Rabdomiólisis/complicaciones , Adolescente , Adulto , Factores de Edad , Cardiomiopatías/diagnóstico , Cardiomiopatías/patología , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Errores Innatos del Metabolismo Lipídico/diagnóstico , Errores Innatos del Metabolismo Lipídico/patología , Masculino , Miopatías Mitocondriales/diagnóstico , Miopatías Mitocondriales/patología , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/patología , Enfermedades del Sistema Nervioso Periférico/patología , Fenotipo , Rabdomiólisis/diagnóstico , Rabdomiólisis/patología , Adulto Joven

RESUMEN

Introduction: LCHADD causes retinopathy associated with low vision, visual field defects, nyctalopia and myopia. We report a retrospective long-term single-center study of 6 LCHADD patients trying to clarify if early diagnosis has an impact on the course and outcome of chorioretinal degeneration. Methods: Long-term follow-up of visual acuity and staging of chorioretinal degeneration by fundus photography, optical coherence tomography (OCT) and autofluorescence (AF) in all six patients. Three patients (2 m/1 f; age 8-14.8 years) were diagnosed by newborn screening, a single patient early within the first year of life and treated promptly while the other two (1 m/1 f; age 23-24 years) were diagnosed later after developing symptoms. All carried HADHA variants; five were homozygous for the common p.E510Q variant, in one from the symptomatically diagnosed group p.[E510Q]; [R291*] was detected. Results: All patients showed retinal alterations, but early diagnosis was associated with a milder phenotype and a longer preservation of visual function. Among symptomatic patients, only one showed mild retinal involvement at the time of diagnosis. Conclusion: Despite the small number our study suggests that early diagnosis does not prevent retinopathy but might contribute to a milder phenotype with retained good visual acuity over time. OCT and AF are reliable non-invasive diagnostic tools to estimate the progression of early-stage retinal changes in LCHADD patients.

Asunto(s)

Cardiomiopatías/patología , Errores Innatos del Metabolismo Lipídico/patología , 3-Hidroxiacil-CoA Deshidrogenasa de Cadena Larga/deficiencia , Miopatías Mitocondriales/patología , Proteína Trifuncional Mitocondrial/deficiencia , Enfermedades del Sistema Nervioso/patología , Rabdomiólisis/patología , Agudeza Visual , Adolescente , Adulto , Cardiomiopatías/genética , Niño , Femenino , Humanos , Errores Innatos del Metabolismo Lipídico/genética , Masculino , Miopatías Mitocondriales/genética , Proteína Trifuncional Mitocondrial/genética , Imagen Multimodal , Enfermedades del Sistema Nervioso/genética , Pronóstico , Estudios Retrospectivos , Rabdomiólisis/genética , Adulto Joven

RESUMEN

Long-chain fatty-acyl CoA dehydrogenase deficiency (LCHADD) is an inborn error of long chain fatty acid oxidation with various features including hypoketotic hypoglycemia, recurrent rhabdomyolysis, pigmentary retinopathy, peripheral neuropathy, cardiomyopathy, and arrhythmias. Various stresses trigger metabolic decompensation. Coronavirus disease 2019 (COVID-19) is a pandemic caused by the RNA virus SARS-CoV-2 with diverse presentations ranging from respiratory symptoms to myocarditis. We report a case of a patient with LCHADD who initially presented with typical metabolic decompensation symptoms including nausea, vomiting, and rhabdomyolysis in addition to mild cough, and was found to have COVID-19. She developed acute respiratory failure and refractory hypotension from severe cardiomyopathy which progressed to multiple organ failure and death. Our case illustrates the need for close monitoring of cardiac function in patients with a long-chain fatty acid oxidation disorder.

RESUMEN

INTRODUCTION: Mitochondrial fatty acid oxidation disorders (FAODs) are a heterogeneous group of hereditary autosomal recessive diseases included in newborn screening (NBS) program in Italy. The aim of this study was to analyse FAODs cases, identified either clinically or by NBS,for clinical and genetic characterization and to evaluate a five years' experience of NBS, in the attempt to figure out the complexity of genotype-phenotype correlation and to confirm the clinical impact of NBS in our centre experience. MATERIALS AND METHODS: We analysed FAODs patients diagnosed either by NBS or clinically, followed since February 2014 to April 2019 at the Regional Screening Centre and Inherited Metabolic Diseases Unit of Verona. Diagnosis was confirmed by plasma acylcarnitines, urinary organic acids, enzymatic and genetic testing. For not clear genotypes due to the presence of variants of uncertain significance, in silico predictive tools have been used as well as enzymatic activity assays. Patients underwent clinical, nutritional and biochemical follow up. RESULTS: We diagnosed 30 patients with FAODs. 20 by NBS: 3 CUD, 6 SCADD, 5 MCADD, 4 VLCADD, 2 MADD. Overall incidence of FAODs diagnosed by NBS was 1:4316 newborns. No one reported complications during the follow up period. 10 patients were diagnosed clinically: 2 CUD, 2 CPT2D, 1 VLCADD, 5 MADD. Mean age at diagnosis was 29.3 years. Within this group, complications or symptoms were reported at diagnosis, but not during follow-up. 12 mutations not previously reported in literature were found, all predicted as pathogenic or likely pathogenic. DISCUSSION AND CONCLUSIONS: Our study highlighted the great phenotypic variability and molecular heterogeneity of FAODs and confirmed the importance of a tailored follow up and treatment. Despite the short duration of follow up, early identification by NBS prevented diseases related complications and resulted in normal growth and psycho-motor development as well.

Asunto(s)

Cardiomiopatías/diagnóstico , Ácidos Grasos/sangre , Errores Innatos del Metabolismo Lipídico/diagnóstico , Miopatías Mitocondriales/diagnóstico , Proteína Trifuncional Mitocondrial/deficiencia , Tamizaje Neonatal/métodos , Enfermedades del Sistema Nervioso/diagnóstico , Rabdomiólisis/diagnóstico , Cardiomiopatías/sangre , Humanos , Fórmulas Infantiles , Recién Nacido , Recien Nacido Prematuro , Errores Innatos del Metabolismo Lipídico/sangre , Masculino , Miopatías Mitocondriales/sangre , Proteína Trifuncional Mitocondrial/sangre , Enfermedades del Sistema Nervioso/sangre , Rabdomiólisis/sangre

RESUMEN

Metabolic disorders, although rare, can involve multiple organ systems and have a varied presentation. Renal involvement has been reported in several metabolic disorders in the pediatric age group. We report a rare metabolic disorder, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, in a child who developed steroid-resistant nephrotic syndrome at the age of 5 years. Renal biopsy showed features of collapsing glomerulopathy. The child had progressive chronic kidney disease. Alternative immunosuppressants including tacrolimus failed to show any clinical improvement. There have been no reports of children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency developing steroid-resistant nephrotic syndrome and collapsing glomerulopathy. This case highlights the need to monitor renal function and proteinuria among this group of children.

Asunto(s)

Cardiomiopatías/complicaciones , Enfermedades Renales/etiología , Glomérulos Renales/patología , Errores Innatos del Metabolismo Lipídico/complicaciones , Miopatías Mitocondriales/complicaciones , Proteína Trifuncional Mitocondrial/deficiencia , Enfermedades del Sistema Nervioso/complicaciones , Rabdomiólisis/complicaciones , Preescolar , Humanos , Enfermedades Renales/patología , Masculino

RESUMEN

Neonates with low birthweight (LBW) represent a vulnerable population. This retrospective study analyzed the birth frequency of diseases detected by neonatal screening (NBS) in normal and LBW neonates in the Czech Republic. Between years 2002 and 2016, the number of screened disorders in the Czech Republic gradually increased from two to 13. Prevalence of screened diseases was calculated for cohorts ranging from 777,100 to 1,277,283 neonates stratified by birthweight. Odds ratio of the association of LBW with each disease was calculated and statistical significance was evaluated using the chi-square test or Fisher's exact test, as appropriate. Three diseases were associated with higher risk of prevalence in LBW neonates, namely congenital hypothyroidism (OR 2.50, CI 1.92; 3.25), cystic fibrosis (OR 2.44, CI 1.51; 3.94), and long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) (OR 7.74, CI 2.18; 27.42).Conclusion: Although the underlying mechanisms are not well understood, results can be hypothesized that LBW (respectively prematurity) may lead to the secondary and often transitory hypothyroidism while cystic fibrosis and LCHADD may manifest already prenatally and result into preterm birth and LBW. What is Known: • The percentage of low birthweight (LBW) neonates in the Czech Republic has been increasing. • Previously published studies reported positive association between LBW and congenital hypothyroidism and cystic fibrosis. What is New: • The association between LCHADD and LBW has not yet been described. • LBW can be the first manifestation of cystic fibrosis and LCHADD.

Asunto(s)

Enfermedades del Recién Nacido/epidemiología , Tamizaje Neonatal/normas , Peso al Nacer , República Checa/epidemiología , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Prevalencia , Estudios Retrospectivos

RESUMEN

Patients affected by long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency predominantly present severe liver and cardiac dysfunction, as well as neurological symptoms during metabolic crises, whose pathogenesis is still poorly known. In this study, we demonstrate for the first time that pathological concentrations of 3-hydroxypalmitic acid (3HPA), the long-chain hydroxyl fatty acid (LCHFA) that most accumulates in LCHAD deficiency, significantly decreased adenosine triphosphate-linked and uncoupled mitochondrial respiration in intact cell systems consisting of heart fibers, cardiomyocytes, and hepatocytes, but less intense in diced forebrain. 3HPA also significantly reduced mitochondrial Ca2+ retention capacity and membrane potential in Ca2+ -loaded mitochondria more markedly in the heart and the liver, with mild or no effects in the brain, supporting a higher susceptibility of the heart and the liver to the toxic effects of this fatty acid. It is postulated that disruption of mitochondrial energy and Ca2+ homeostasis caused by the accumulation of LCHFA may contribute toward the severe cardiac and hepatic clinical manifestations observed in the affected patients.

Asunto(s)

Hepatocitos/metabolismo , Mitocondrias/efectos de los fármacos , Mioblastos Cardíacos/metabolismo , Ácidos Palmíticos/efectos adversos , Adenosina Trifosfato/metabolismo , Animales , Encéfalo/citología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Calcio/metabolismo , Línea Celular , Células Hep G2 , Hepatocitos/citología , Hepatocitos/efectos de los fármacos , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Mioblastos Cardíacos/citología , Mioblastos Cardíacos/efectos de los fármacos , Ratas , Ratas Wistar

RESUMEN

BACKGROUND: Children with long-chain fatty acid ß-oxidation disorders (LCFAOD) presenting with clinical symptoms are treated with a specialist infant formula, with medium chain triglyceride (MCT) mainly replacing long chain triglyceride (LCT). It is essential that the safety and efficacy of any new specialist formula designed for LCFAOD be tested in infants and children. METHODS: In an open-label, 21-day, phase I trial, we studied the safety of a new MCT-based formula (feed 1) in six well-controlled children (three male), aged 7-13 years (median 9 years) with LCFAOD (very long chain acyl CoA dehydrogenase deficiency [VLCADD], n=2; long chain 3-hydroxyacyl CoA dehydrogenase deficiency [LCHADD], n=2; carnitine acyl carnitine translocase deficiency [CACTD], n=2). Feed 1 (Lipistart; Vitaflo) contained 30% energy from MCT, 7.5% LCT and 3% linoleic acid and it was compared with a conventional MCT feed (Monogen; Nutricia) (feed 2) containing 17% energy from MCT, 3% LCT and 1.1% linoleic acid. Subjects consumed feed 2 for 7 days then feed 1 for 7 days and finally resumed feed 2 for 7 days. Vital signs, blood biochemistry, ECG, weight, height, food/feed intake and symptoms were monitored. RESULTS: Five subjects completed the study. Their median daily volume of both feeds was 720 mL (range 500-1900 mL/day). Feed 1 was associated with minimal changes in tolerance, free fatty acids (FFA), acylcarnitines, 3-hydroxybutyrate (3-HB), creatine kinase (CK), blood glucose, liver enzymes and no change in an electrocardiogram (ECG). No child complained of muscle pain or symptoms associated with LCFAOD on either feed. CONCLUSIONS: This is the first safety trial reported of an MCT formula specifically designed for infants and children with LCFAOD. In this short-term study, it appeared safe and well tolerated in this challenging group.

Asunto(s)

3-Hidroxiacil-CoA Deshidrogenasas/deficiencia , Acil-CoA Deshidrogenasa de Cadena Larga/deficiencia , Carnitina Aciltransferasas/deficiencia , Errores Innatos del Metabolismo Lipídico/dietoterapia , Enfermedades Mitocondriales/dietoterapia , Enfermedades Musculares/dietoterapia , Triglicéridos/administración & dosificación , Adolescente , Niño , Síndromes Congénitos de Insuficiencia de la Médula Ósea , Femenino , Humanos , Masculino , Triglicéridos/efectos adversos

RESUMEN

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a rare genetic disease. The LCHADD treatment is mainly based on special diet. In this diet, energy from long-chain triglycerides (LCT) cannot exceed 10%, however energy intake from the consumption of medium-chain triglycerides (MCTs) should increase. The daily intake of energy should be compatible with energy requirements and treatment should involve frequent meals including during the night to avoid periods of fasting. In fact, there are no recommendations for total content of LCT in all of the allowed food in the LCHADD diet. The aim of the study was to present a new method of diet composition in LCHADD with the use of blocks based on energy exchangers with calculated LCT content. In the study, the diet schema was shown for calculating the energy requirements and LCT content in the LCHADD diet. How to create the diet was also shown, based on a food pyramid developed for patients with LCHADD. The blocks will make it possible, in a quick and simple way, to create a balanced diet which provides adequate energy value, essential nutrients and LCT content. This method can be used by doctors and dietitians who specialize in treating rare metabolic diseases. It can also be used by patients and their families for accurate menu planning with limited LCT content.

Asunto(s)

3-Hidroxiacil-CoA Deshidrogenasas/deficiencia , Cardiomiopatías/dietoterapia , Ingestión de Energía/fisiología , Errores Innatos del Metabolismo Lipídico/dietoterapia , Miopatías Mitocondriales/dietoterapia , Proteína Trifuncional Mitocondrial/deficiencia , Enfermedades del Sistema Nervioso/dietoterapia , Rabdomiólisis/dietoterapia , Triglicéridos/metabolismo , Adulto , Anciano , Cardiomiopatías/metabolismo , Niño , Preescolar , Dieta/métodos , Femenino , Humanos , Lactante , Recién Nacido , Errores Innatos del Metabolismo Lipídico/metabolismo , Masculino , Persona de Mediana Edad , Miopatías Mitocondriales/metabolismo , Proteína Trifuncional Mitocondrial/metabolismo , Enfermedades del Sistema Nervioso/metabolismo , Rabdomiólisis/metabolismo , Adulto Joven

RESUMEN

In this report we describe a female Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHADD) patient who suffered from severe exercise intolerance. At age 34, the patient became pregnant for the first time. After an uneventful first 32 weeks of pregnancy she developed sinus tachycardia (resting heart rate 120-134 bpm) and lactate and creatinine kinase levels increased (3.3 mmol/L and 264 U/L, respectively). Increasing MCT supplementation (dose and frequency of administration) lowered heart rate and improved biochemical parameters. At 34 weeks the heart rate rose again and it was decided to deliver the child by caesarean section. Postpartum both mother and child did well.Prior to pregnancy, she performed exercise tests with different doses of medium chain triglycerides (MCTs) to establish a safe and effective exercise program (baseline test, second test with 10 g MCTs and third test with 20 g of MCTs). In the MCT supplemented tests the maximal power output was 23% (second test) and 26% (third test) higher, while cardiac output at maximal power output was the same in all three tests (~15.8 L/min).In conclusion, this is the first report of pregnancy in an LCHADD patient, with favourable outcome for both mother and child. Moreover, in the same patient, MCT supplementation improved cardiac performance and metabolic parameters during high intensity exercise. Using impedance cardiography, we got a clear indication that this benefit was due to improved muscle energy generation at high intensity exercise, since at the same cardiac output a higher power output could be generated.

RESUMEN

AIM: There have been few studies on long-term electroretinographic findings in patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). This study correlated long-term electroretinographic findings with age, metabolic control and clinical symptoms. METHODS: We examined 12 Swedish patients with LCHADD. Visual acuity testing, fundus examinations, optical coherence tomography and electroretinography were performed. The results were correlated to age, the levels of 3-hydroxyacylcarnitine and acylcarnitine and clinical metabolic control. RESULTS: Blindness or moderate visual impairment was found in two patients. Retinal pigmentation, atrophy and fibrosis were present in 11, seven and one of the patients, respectively, and optical coherence tomography showed retinal thinning in three of the six patients examined. Electroretinography was performed on 11 of the 12 patients. It was pathological, with reduced rod and cone responses, in five patients, subnormal in four and was related to poor clinical metabolic control and severe neonatal symptoms. Repeated electroretinographies revealed reduced function with increasing age. CONCLUSION: More than 80% of the LCHADD patients developed pathological or subnormal retinal function. This was more pronounced in patients with neonatal symptoms, but ameliorated by strict dietary treatment. Annual ophthalmological follow-ups, with electroretinography every second or third year, are recommended.

Asunto(s)

Cardiomiopatías/complicaciones , Electrorretinografía , Errores Innatos del Metabolismo Lipídico/complicaciones , Miopatías Mitocondriales/complicaciones , Proteína Trifuncional Mitocondrial/deficiencia , Enfermedades del Sistema Nervioso/complicaciones , Enfermedades de la Retina/etiología , Rabdomiólisis/complicaciones , Adolescente , Adulto , Cardiomiopatías/dietoterapia , Cardiomiopatías/fisiopatología , Niño , Preescolar , Estudios de Cohortes , Humanos , Errores Innatos del Metabolismo Lipídico/dietoterapia , Errores Innatos del Metabolismo Lipídico/fisiopatología , Masculino , Miopatías Mitocondriales/dietoterapia , Miopatías Mitocondriales/fisiopatología , Enfermedades del Sistema Nervioso/dietoterapia , Enfermedades del Sistema Nervioso/fisiopatología , Enfermedades de la Retina/diagnóstico , Rabdomiólisis/dietoterapia , Rabdomiólisis/fisiopatología , Adulto Joven

RESUMEN

CLINICAL CASE: A five-year-old patient, with a diagnosis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, was referred for an ophthalmological examination. He had a history of acute metabolic crises precipitated by intercurrent infections,as well as rhabdomyolysis. The fundoscopic examination revealed a peripapillary chorioretinal atrophy and a diffuse granular appearance of the macular retinal pigment epithelium. Best corrected visual acuity was 6/6 in both eyes, and he had a normal electroretinography test. DISCUSSION: We perform a review of the literature and recent findings in relation to this disease through the description of a clinical case in order to improve the knowledge of this uncommon disorder.

Asunto(s)

Cardiomiopatías , Errores Innatos del Metabolismo Lipídico , Miopatías Mitocondriales , Proteína Trifuncional Mitocondrial/deficiencia , Enfermedades del Sistema Nervioso , Rabdomiólisis , Cardiomiopatías/diagnóstico por imagen , Preescolar , Humanos , Errores Innatos del Metabolismo Lipídico/diagnóstico por imagen , Masculino , Miopatías Mitocondriales/diagnóstico por imagen , Enfermedades del Sistema Nervioso/diagnóstico por imagen , Rabdomiólisis/diagnóstico por imagen