Analysis of 6 cases with hepatocerebral mitochondrial DNA depletion syndrome and literature review / 中华儿科杂志

Objective: To explore the clinical features of hepatocerebral mitochondrial DNA depletion syndrome (MDS). Methods: The clinical data of 6 hepatocerebral MDS patients diagnosed in the Jinshan Hospital of Fudan University from January 2012 to December 2019 were retrospectively collected and analyzed. Related literature published before January 2020 were searched with the key words of "DGUOK""MPV17""POLG""C10orf2" in PubMed, China national knowledge infrastructure (CNKI) and Wanfang database. Results: All the 6 hepatocerebral MDS cases were male. The age of onset ranged from 3 days to 8 months. The most common initial symptoms were cholestasis and developmental retrogression. The main clinical manifestations included hepatomegaly (4 cases), hypotonia (3 cases), growth retardation (4 cases), cholestasis (5 cases), coagulopathy (5 cases), hypoalbuminemia (3 cases), hypoglycemia (4 cases), hyperlactacidemia (5 cases), and abnormal blood metabolism screening (6 cases). The isotope hepatobiliary imaging revealed no gallbladder and intestinal tract development within 24 hours in 2 patients. Regarding the cranial imaging examination, the head CT found widening of the extracranial space in 1 case, the brain magnetic resonance imaging (MRI) found ventricular enlargement in 2 cases, and the brain ultrasound found peripheral white matter injury in 1 case. Two cases were lost to follow-up, one died of liver failure, and three died of multiple organ failure due to aggravated infection. Among the 6 cases, there were 3 with MPV17 variation (c.182T>C and c.279G>C were novel), 1 with POLG variation (c.2993G>A was novel), 1 with DGUOK variation (c.679G>A homozygous mutation, parthenogenetic diploid of chromosome 2) and 1 with C10orf2 variation (c.1186C>T and c.1504C>T were novel). The literature review found that 129, 100, 51 and 12 cases of hepatocerebral MDS were caused by DGUOK, MPV17, POLG and C10orf2 gene variations, respectively. And the most common clinical manifestations were liver dysfunction presented with cholestasis and elevated transaminase, metabolic disorders including hypoglycemia and hyperlactacidemia, and diverse neurologic symptoms including developmental retardation, hypotonia, epilepsy and peripheral neuropathy. Besides, 1/3 of the patients with C10orf2 variation developed renal tubular injury. Conclusions: Hepatocerebral MDS mainly present with liver dysfunction, metabolic disorder and neuromuscular impairment. Different genotypes show specific clinical manifestations.

Analysis of a child with carnitine palmitoyl transferase 1A deficiency due to variant of CPT1A gene / 中华医学遗传学杂志

OBJECTIVE@#To report on the clinical, metabolic and genetic characteristics of a child with carnitine palmitoyl transferase 1A (CPT1A) deficiency.@*METHODS@#Clinical data and the level of acylcarnitine for a child who initially presented as epilepsy were analyzed. Genomic DNA was extracted from peripheral blood samples of the child and her parents and subjected to next-generation sequencing (NGS).@*RESULTS@#Mass spectrometry of blood acylcarnitine indicated increased carnitine 0 (C0) and significantly increased C0/ (C16+C18). DNA sequencing revealed that the child has carried compound heterozygous variants of the CPT1A gene, namely c.1846G>A and c.2201T>C, which were respectively inherited from her mother and father.@*CONCLUSION@#CPT1A presenting initially as epilepsy was unreported previously. Analysis of blood acylcarnitine C0 and C0/ (C16 + C18) ratio and NGS are necessary for the identification and diagnosis of CPT1A deficiency. The c.1846G>A and c.2201T>C variants of the CPT1A gene probably underlay the disease in this child. Above finding has also enriched the spectrum of CPT1A gene variants.

Energy intake underreporting of adults in a household survey: the impact of using a population specific basal metabolic rate equation / Subestimativa da ingestão energética em amostra probabilística de adultos: o impacto do uso de equações específicas para taxa metabólica basal / Subestimación de la ingesta energética en una muestra probabilística de adultos: el impacto del uso de ecuaciones específicas para la tasa metabólica basal

The purpose of the present study was to identify energy intake (EI) underreporting and to estimate the impact of using a population specific equation for the basal metabolic rate (BMR) in a probability sample of adults from Niterói, Rio de Janeiro State, Brazil. A sample of 1,726 subjects participated in the study. EI was assessed by a 24-hour dietary recall and EI/BMR was computed with BMR estimated using internationally recommended equations as well as specific equations developed for the adult population of Niterói. Mean EI was 1,570.9 and 2,188.8kcal.day-1 for women and men, respectively. EI decreased with increasing age in both men and women. BMR estimated by the Brazilian equation was significantly lower than the values estimated by the international equation for all age, sex and nutritional status groups. In general, EI underreporting was found in at least 50% of the population, higher in women, and increased with increasing age and body mass index (BMI). The results of the present study confirm that EI is underreported, even when BMR is estimated using population-specific equations.

O objetivo do presente estudo foi identificar a subestimativa da ingestão energética (IE) e estimar o impacto do uso de uma equação específica da população para a taxa metabólica basal (TMB), em amostra probabilística de adultos do Município de Niterói, Rio de Janeiro, Brasil. Uma amostra de 1.726 indivíduos da população adulta participou do estudo. Ingestão energética foi avaliada por um recordatório de 24 horas e IE/TMB foi calculada com TMB estimada pelas equações recomendadas e pelas equações específicas para a população. A média da IE foi 1.570,9 e 2.188,8kcal.dia-1 em mulheres e homens, respectivamente. A ingestão energética diminuiu com o aumento da idade em homens e mulheres. A taxa metabólica basal estimada pela equação brasileira foi significativamente menor do que os valores estimados pela equação recomendada para todas as idades, sexo e estado nutricional. Em geral, a subestimativa da IE foi encontrada em pelo menos 50% da população, maior em mulheres, e aumentou com o avanço da idade e índice de massa corporal (IMC). Os resultados confirmam que IE é subestimada, mesmo quando a TMB é estimada pelas equações da população específica.

El objetivo del presente estudio fue identificar la subestimación de la ingesta energética (IE) y estimar el impacto del uso de una ecuación específica de la población para la tasa metabólica basal (TMB), en una muestra probabilística de adultos del municipio de Niterói, Río de Janeiro, Brasil. Una muestra de 1.726 individuos de la población adulta participó en el estudio. La ingesta energética fue evaluada mediante un recordatorio de 24 horas y las IE/TMB fueron calculadas con una TMB estimada por las ecuaciones recomendadas y por las ecuaciones específicas para la población. La media de la IE fue 1.570,9 y 2.188,8kcal.día-1 en mujeres y hombres, respectivamente. La ingesta energética disminuyó con el aumento de la edad en hombres y mujeres. La tasa metabólica basal estimada por la ecuación brasileña fue significativamente menor que los valores estimados por la ecuación recomendada para todas las edades, sexo y estado nutricional. En general, la subestimación de la IE se encontró en por lo menos un 50% de la población, fue mayor en mujeres y aumentó con el aumento de la edad e índice de masa corporal (IMC). Los resultados confirman que la IE está subestimada, incluso cuando la TMB está estimada por las ecuaciones de población específica.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome due to a mutation in the glutamate dehydrogenase gene / Síndrome de hiperinsulinemia/hiperamonemia devido a uma mutação no gene da glutamato desidrogenase

The hyperinsulinism/hyperammonemia (HI/HA) syndrome is a rare autosomal dominant disease manifested by hypoglycemic symptoms triggered by fasting or high-protein meals, and by elevated serum ammonia. HI/HA is the second most common cause of hyperinsulinemic hypoglycemia of infancy, and it is caused by activating mutations in GLUD1, the gene that encodes mitochondrial enzyme glutamate dehydrogenase (GDH). Biochemical evaluation, as well as direct sequencing of exons and exon-intron boundary regions of the GLUD1 gene, were performed in a 6-year old female patient presenting fasting hypoglycemia and hyperammonemia. The patient was found to be heterozygous for one de novo missense mutation (c.1491A>G; p.Il497Met) previously reported in a Japanese patient. Treatment with diazoxide 100 mg/day promoted complete resolution of the hypoglycemic episodes. Arq Bras Endocrinol Metab. 2012;56(8):485-9.

A síndrome de hiperinsulinemia/hiperamonemia (HI/HA) é uma condição rara, de herança autossômica dominante, que se manifesta por sintomas de hipoglicemia desencadeada por jejum ou refeições de alto conteúdo proteico, juntamente com elevação da concentração de amônia sérica. HI/HA é a segunda causa de hipoglicemia hiperinsulinêmica da infância e é causada por mutações ativadoras no GLUD1, o gene que codifica a enzima mitocondrial glutamato desidrogenase (GDH). A avaliação bioquímica, bem como o sequenciamento direto dos éxons e junções éxon-íntron do gene GLUD1, foi realizada em uma paciente de 6 anos de idade com hipoglicemia de jejum e hiperamonemia. A paciente apresentava uma mutação de novo missense (c.1491A>G; p.Il497Met) em heterozigose, que havia sido previamente relatada em um paciente japonês. O tratamento com diazóxido 100 mg/dia promoveu resolução completa dos episódios hipoglicêmicos. Arq Bras Endocrinol Metab. 2012;56(8):485-9.

Hipoglicemia secundaria a hipopituitarismo congénito / Hypoglycemia secundary a congenital hipopituitarism

La hipoglicemia es la manifestación inicial de los pacientes con hipopituitarismo congénito, especialmente en el período neonatal, en la mayoría de los casos se asocia a defectos en la línea media, sin déficid pondoestatural al momento del nacimiento, ni en los primeros meses de vida. Se presenta el caso de lactante mayor con hipoglicemia y convulsiones generalizadas, sin alteraciones al examen físico. El perfil endocrinológico reportó insuficiencia hipofisiaria