Keto-Sleuths - An Unusual Cause of Loss of Ketosis?

Ketogenic diets provide a non-pharmaceutical alternative for treatment of refractory epilepsy. When successful in reducing or eliminating seizures, medication numbers or doses may be reduced. Unexpected loss of ketosis is a common problem in management of patients on ketogenic diets and, especially when the diet is an effective treatment, loss of ketosis may be associated with an exacerbation in seizures. Identification of the cause of loss of ketosis is critical to allow rapid resumption of seizure control, and prevention of unnecessarily increased diet restriction or increased medication doses. Here an unusual environmental cause of loss of ketosis is described (contamination with starch-containing drywall dust), illustrating the extent of investigation sometimes necessary to understand the clinical scenario.

Use of skimmed breast milk for an infant with a long-chain fatty acid oxidation disorder: A novel therapeutic intervention.

The focus of dietary therapy for long chain fatty acid oxidation disorders (LC-FAODs) is to minimize fatty acid oxidation by avoiding fasting and providing sufficient calories. Dietary therapy involves restriction of long-chain triglycerides (LCT), and provision of medium-chain triglycerides as an alternate energy source. It is well established that the use of breast milk through the first year of a newborn's life has significant health benefits. While very few medical contraindications to breastfeeding exist, feeding an infant with a severe carnitine acylcarnitine translocase (CACT) deficiency typically requires cessation of breastfeeding as approximately 50% of the calories in human milk come from LCT. In this case report, we present the innovative and successful use of skimmed breast milk incorporated into the dietary management of an infant with severe CACT deficiency. Given the poor prognosis for individuals with severe CACT deficiency on standard dietary therapy, the use of skimmed breast milk represents an important measure to try to improve short-term and long-term outcomes. Given the many proven benefits of breast milk, this case illustrates that skimmed breast milk can be combined with appropriate fat sources to provide complete nutrition for children with severe CACT deficiency. After over 12 months on this regimen, this patient has experienced normal growth and development and has had no acute decompensations.

Ketogenic diet in Zambia: Managing drug-resistant epilepsy in a low and middle income country.

Globally, drug-resistant epilepsy affects one third of people living with epilepsy. With limitations in treatment options for refractory epilepsy in resource-limited regions, ketogenic diet therapy is an important option to consider. Utilizing the 2015 International League Against Epilepsy recommended minimum requirements for ketogenic diet therapy, three male children with refractory epilepsy, aged 2.5, 6.5 and 10 years, were initiated on the classical ketogenic diet using locally available food in August 2017 at University Teaching Hospitals-Children's Hospital in Lusaka, Zambia, through partnership with the Epilepsy Program at Boston Children's Hospital in the United States. Following successful initiation in all three children, the diet was discontinued in the 10-year-old due to difficulties complying with the diet. The youngest child demonstrated an over 50% seizure reduction and gained developmental milestones. The third child achieved seizure freedom and showed marked improvement in behaviour. This pilot demonstrates the feasibility of ketogenic diet as an important therapeutic option for refractory epilepsy in Zambia. Given the limitations in treatment choices and medication accessibility, dietary therapy offers an alternative management strategy in our setting. Collaboration with an established ketogenic diet centre contributes to a successful program.

A novel null mutation in the pyruvate dehydrogenase phosphatase catalytic subunit gene (PDP1) causing pyruvate dehydrogenase complex deficiency.

Congenital lactic acidosis due to pyruvate dehydrogenase phosphatase (PDP) deficiency is very rare. PDP regulates pyruvate dehydrogenase complex (PDC) and defective PDP leads to PDC deficiency. We report a case with functional PDC deficiency with low activated (+dichloroacetate) and inactivated (+fluoride) PDC activities in lymphocytes and fibroblasts, normal activity of other mitochondrial enzymes in fibroblasts, and novel biallelic frameshift mutation in the PDP1 gene, c.575dupT (p.L192FfsX5), with absent PDP1 product in fibroblasts. Unexpectedly, the patient also had low branched-chain 2-ketoacid dehydrogenase (BCKDH) activity in fibroblasts with slight elevation of branched-chain amino acids in plasma and ketoacids in urine but with no pathogenic mutations in the enzymes of BCKDH, which could suggest shared regulatory function of PDC and BCKDH in fibroblasts, potentially in other tissues or cell types as well, but this remains to be determined. The clinical presentation of this patient overlaps that of other patients with primary-specific PDC deficiency, with neonatal/infantile and childhood lactic acidosis, normal lactate to pyruvate ratio, elevated plasma alanine, delayed psychomotor development, epileptic encephalopathy, feeding difficulties, and hypotonia. This patient exhibited marked improvement of overall development following initiation of ketogenic diet at 31 months of age. To the best of our knowledge, this is the fourth case of functional PDC deficiency with a defined mutation in PDP1. SYNOPSIS: Pyruvate dehydrogenase phosphatase (PDP) regulates pyruvate dehydrogenase complex (PDC) and defective PDP due to PDP1 mutations leads to PDC deficiency and congenital lactic acidosis.

Comprehensive nutritional and metabolic assessment in patients with spinal muscular atrophy: Opportunity for an individualized approach.

Optimal nutrition support is recommended for patients with spinal muscular atrophy (SMA). In a prospective study, we performed comprehensive nutritional assessments with the aim to guide best nutritional strategies for patients with SMA types II and III. We recorded a) anthropometry; b) macro- and micronutrient intakes; c) measured resting energy expenditure by indirect calorimetry; and d) body composition including dual X-ray absorptiometry. We enrolled a cohort of 21 patients aged 3 to 36 years of which 13 were female; 19 had SMA type II and 2 had SMA type III. The body mass index z-score ranged from -3 to 2.4. Forty-five percent of the cohort was either underfed or overfed, based on the difference between actual energy intake and measured resting energy expenditure. Vitamin D, E, K, folate and calcium intakes were low in a majority of the cohort. Forty-five percent of the cohort was either hypometabolic or hypermetabolic. Fat mass index (kg/m2) was significantly higher and lean body mass index (kg/m2) was significantly lower in the study cohort compared to population normalized values. Bone mineral density was low in 13 of 17 patients. In summary, we have described the prevalence of malnutrition, suboptimal feeding and alterations in body composition in children with SMA. A comprehensive nutritional assessment could guide individualized nutrition therapy in this vulnerable population.

Nutritional Status and Nutrient Intake Challenges in Children With Spinal Muscular Atrophy.

BACKGROUND: Nutrition is recognized as a core component of multidisciplinary care for patients with spinal muscular atrophy, but specific nutritional challenges in this population are not well described. We aimed to describe the nutritional status and nutrient intake in children with spinal muscular atrophy. METHODS: We performed a retrospective medical record review of prospectively collected data from children with spinal muscular atrophy followed at a multidisciplinary clinic at a tertiary referral center. We collected data including clinical parameters; anthropometrics, including weight, height, and body mass index (BMI); and 24-hour dietary intake records in all children followed in the clinic. Available data were found in records from the dietitian as part of a standard evaluation process, and additional clinical data were acquired from patient medical records. Subjects were classified based on spinal muscular atrophy type, and nutritional intake data were compared with dietary reference intakes for gender and age. Z-scores were calculated for weight for age (WAZ), height for age, and BMI (BMIZ) using the World Health Organization AnthroPlus software with appropriate World Health Organization reference growth standards. Subjects were classified as malnourished if their WAZ was <-2 or >+2. Anthropometric measurements were obtained at first visit and at a follow-up visit at an average of a 3-year interval between the clinic visits. A decline of more than 0.5 WAZ over this period was defined a priori as significant nutritional deterioration. RESULTS: We analyzed data from 60 subjects, 26 (43%) female, with median age 5.5 years (interquartile range 2 years to 12 years). The cohort consisted of children with spinal muscular atrophy type 1 (28 %), type 2 (45 %), and type 3 (27 %). At the first clinic visit, nine (15%) patients were malnourished. Thirteen (23%) subjects had a significant decline in WAZ from -0.35 (-1.31 to 0.58) to -1.04 (-2.15 to 0.02) at follow-up after approximately 3 years. A third of these subjects were already malnourished at first visit. A significant decline in BMIZ was noted in 47% of the cohort, and the prevalence of severe malnutrition (BMIZ < -3) increased from 2% to 17% after 3 years. In children receiving specialized enteral nutrition via a feeding tube, overfeeding was recorded in 29% and underfeeding was recorded in 35%. Suboptimal vitamin D intake was recorded in 35% of patients with enteral feeding device. CONCLUSIONS: Malnutrition was prevalent in children with spinal muscular atrophy, and nearly half the cohort demonstrated nutritional deterioration over time. Energy, protein, and vitamin D intakes were inadequate in a majority of the cohort. Underfeeding was highly prevalent, but overfeeding was also present in a third of the enterally fed cohort. Future studies describing optimal nutrient requirements and body composition variables in this group are required.