Narumon Densupsoontorn

Carnitine–acylcarnitine translocase deficiency: Two neonatal cases with common splicing mutation and in vitro bezafibrate response

BACKGROUND Mitochondrial fatty acid oxidation (FAO) disorders are among the causes of acute encephalopathy- or myopathy-like illness. Carnitine-acylcarnitine translocase (CACT) deficiency is a rare FAO disorder, which represent an energy production insufficiency during prolonged fasting, febrile illness, or increased muscular activity. CACT deficiency is caused by mutations of the SLC25A20 gene. Most patients developed severe metabolic decompensation in the neonatal period and died in infancy despite aggressive treatment. PATIENTS AND METHODS We herein report the clinical findings of two unrelated cases of CACT deficiency with mutation confirmation, and in vitro bezafibrate responses using in vitro probe acylcarnitine (IVP) assay. Patients 1 and 2 are products of nonconsanguineous parents. Both patients developed cardiac arrest at day 3 of life but survived the initial events. Their blood chemistry revealed hypoglycemia and metabolic acidosis. The acylcarnitine profiles in both patients demonstrated increased long-chain acylcarnitines, suggesting CACT or carnitine palmitoyltransferase-2 (CPT2) deficiency. RESULTS The mutation analysis identified homozygous IVS2-10T>G in the SLC25A20 gene in both patients, confirming the diagnosis of CACT deficiency. The IVP assay revealed increased C16, C16:1, but decreased C2 with improvement by bezafibrate in the cultured fibroblasts. The short-term clinical trial of bezafibrate in Patient 1 did not show clinical improvement, and died after starting the trial for 6 months. CONCLUSION This splicing mutation has been identified in other Asian populations indicating a possible founder effect. IVP assay of cultured fibroblasts could determine a response to bezafibrate treatment. A long-term clinical trial of more enrolled patients is required for evaluation of this therapy.

Fat-soluble vitamins and plasma and erythrocyte membrane fatty acids in chylothorax pediatric patients receiving a medium-chain triglyceride-rich diet.

Post-operative chylothorax can be cured by a medium-chain triglyceride (MCT)-rich diet. However, there is concern that an MCT-rich diet results in clinical and biochemical deficiencies in fat-soluble vitamins and fatty acids. We compared fat-soluble vitamins status and fatty acids status before and after administration of an MCT-rich diet. Nine children with congenital heart disease developed chylothorax after cardiac surgery. Blood samples were drawn from each subject twice, first prior to administration of an MCT-rich diet and secondly when the chylothorax was clinically cured and the MCT diet discontinued. Both blood samples were analyzed for retinol and 25-hydroxy vitamin D concentrations, the ratio of α-tocopherol to total lipids (α-TE/TL), coagulogram, and the fatty acid composition in plasma and erythrocyte membrane phospholipids. In spite of a decrease in the α-TE/TL ratio (3.78 ± 0.89 vs 2.36 ± 0.44 mg/g, p<0.05), this decrease did not reach the deficiency cut-off level. Linoleic acid in both plasma and erythrocyte membrane lipids decreased significantly (25.25 ± 8.06 vs 14.25 ± 2.88%, and 11.19 ± 2.15 vs 6.89 ± 2.45%, respectively). Administration of an MCT-rich diet for treatment of postoperative chylothorax caused a reduction in vitamin E status and linoleic acid, but without any symptoms of deficiency.

Micronutrient deficiencies in obese Thai children

We reported the cases of 3 obese children who presented variously with costochondral beading, numbness of both hands and feet, and hypochromic-microcytic anemia. Serum ascorbic acid concentration, erythrocyte thiamin pyrophosphate effect, and serum hepcidin concentration were done to investigate these symptoms, respectively, with findings of ascorbic acid insufficiency, thiamin deficiency, and iron deficiency anemia from poor iron absorption due to a hyper-inflammatory state, respectively. This report indicated that obese children not only have energy excess but may also risk being micronutrient deficiencies; therefore, weight management with special attention to an adequate intake of vitamins and minerals should be provided.

Imerslund–Gräsbeck syndrome: New mutation in amnionless

Vitamin B12, cobalamin (Cbl), is one of the essential vitamins and its dietary sources are meat, poultry, liver, fish, shellfish, egg, and milk. Cbl deficiency is attributable to various causes including inadequate intake, defects in absorption and transport, and disorders of Cbl metabolism. Imerslund–Grasbeck syndrome (IGS), first reported in 1960, is characterized by Cbl deficiency and proteinuria. 1,2 Most of the initial cases were Finnish and Norwegian, 3 but this syndrome has since been reported throughout Europe, the mid-east and North America, and in patients of African ancestry. 4,5 Bi-allelic mutations in either the cubilin (CUBN )o ramnionless (AMN) gene are responsible for this syndrome. The encoded proteins cubilin and amnionless form the receptor to transport the intrinsic factor-cobalamin (IF-B12) complex into the enterocytes in the terminal ileum. Therefore, defects in either cubilin or amnionless result in Cbl malabsorption. We report a Thai boy with IGS in whom a deleterious mutation in AMN was confirmed. Case report

Improved Tolerance to a New Amino Acid–Based Formula by Infants With Cow’s Milk Protein Allergy

BACKGROUND Prevalence and severity of cows milk protein allergy (CMA) in infants are increasing. A proportion of infants with CMA still elicit signs and symptoms of CMA while ingesting commercial amino acid-based formulas (AAFs). We propose that protein in glucose polymers (GPs) derived from corn starch in the AAFs might be the cause of intolerance to AAF in some infants. We thus have produced small molecules of GPs from rice starch, eliminating the protein fraction from them, and subsequently used them as the sole source of carbohydrate in a new amino acid-based formula (NAAF). METHODS The efficacy of the NAAF was compared with that of an AAF in a double-blind, placebo-controlled food challenge (DBPCFC) in young infants with CMA aged <4 months. Infants consumed each formula for 14 days before switching to the other one. If no respiratory, dermatologic, and gastrointestinal symptom occurred, it was considered tolerance. After the challenge, infants consumed the tolerated formula for 4 weeks to prove real tolerance to that formula. RESULTS Of 46 infants, 23 were intolerant to the AAF, of whom 7 (30.4%) were also intolerant to the NAAF. Sixteen of the 23 infants who were intolerant to the AAF could tolerate the NAAF ( P < .05). The minimal important difference of decreasing percentage of intolerance to the NAAF was 34.8% compared with the infants who were intolerant to the AAF. CONCLUSION The NAAF is better tolerated than a commercially available AAF for the management of infants with CMA.

Diencephalic syndrome due to astrocytoma in three infants with failure to thrive

Diencephalic syndrome (DS) is a group of conditions characterized by major features (severe emaciation despite normal or slightly decreased caloric intake, locomotor hyperactivity and euphoria) and minor features (skin pallor without anemia, hypoglycemia and hypotension). 1 Most of the reported cases showed clinical symptoms before the age of 2 years. An early sign of nystagmus leads to early recognition of this condition.We report three infants with poor oral intake, failure to thrive and nystagmus who were diagnosed with DS due to astrocytoma. The major point of this report emphasizes the recommendation that brain tumor should be thought to be a cause of unexplained failure of physical growth in infants. Patient 1 A 1-year-old female infant with failure to gain weight since the age of 7 months was brought to our hospital due to a need for another opinion. At 6 months of age, she developed poor oral intake and vomiting while being provided with a cow’s milkbased infant formula. Diagnosis of cow’s milk protein allergy (CMPA) was made by a primary physician.Although such cow’s milk-based infant formula was eliminated and an extensively hydrolyzed casein formula (EHF) was introduced, she still consumed little volume and vomited. On detailed history taking, the presence of involuntary rapid eye movement for 5 months led to suspicion of brain tumor; then nystagmus and atrophy of the left optic disc were detected. Her growth parameters are shown in Table 1. Investigations for panhypopituitarism and tumor markers were negative. Cranial computerized tomography (CT) revealed an illdefined non-enhancing hypodense lesion at the suprasellar region measuring 3.8 ¥ 3.8 cm in diameter with the absence of calcification. Subsequently, magnetic resonance imaging (MRI) of the brain revealed a well-defined, lobulated mass at the suprasellar region, involving the optic nerve, optic chiasm and hypothalamus with neither calcification nor a cystic component (Fig. 1). A spinal MRI demonstrated spinal metastasis at multi-levels of the cervical-thoracic-lumbar vertebra to the conus medullaris. Tumor biopsy was performed and the pathological report showed pilomyxoid astrocytoma (World Health Organization (WHO) grade II). Subtotal tumor removal was then performed. Enteral feeding with a medical formula had been provided via a nasogastric tube in combination with parenteral nutrition since admission. Chemotherapy consisting of vincristine and carboplatin was administered. After the operation, panhypopituitarism developed and was subsequently treated. Unfortunately, blindness also occurred. Appetite gradually increased and she could eat orally, so enteral feeding and parenteral nutrition were ceased. Five months later, her weight and length gain were 1720 g and 2 cm, respectively. After 11 months of treatment, cranial and spinal MRI showed a decrease in size of the suprasellar mass and no detectable tumor seeding at the cerebrospinal fluid (CSF) pathway. Patient 2