Intestinal hypomagnesemia in an Iranian patient with a novel TRPM6 variant: a case report and review of the literature.

TRPM6 is predominantly expressed in the kidney and colon and encodes a protein containing an ion channel domain and a protein kinase domain. It is crucial for magnesium homeostasis and plays important roles in epithelial magnesium transport and the active magnesium absorption. In this study, we present a 70-day-old Iranian female patient from consanguineous parents with hypomagnesemia and secondary hypocalcemia. She presented with seizures 19 days after birth and refractory watery non-bloody diarrhea. She consequently had failure to thrive. Other features included hypotonia, wide anterior fontanel, ventriculomegaly, and pseudotumor cerebri following administration of nalidixic acid. She had severe hypomagnesemia and hypocalcemia which were treated with magnesium and calcium supplementation. Despite initial unstable response to supplemental magnesium, she eventually improved and the diarrhea discontinued. The patient was discharged by magnesium and calcium therapy. At the last follow-up at age 2.5 years, the patient remained well without any recurrence or complication. Genetic testing by whole-exome sequencing revealed a novel homozygous frameshift insertion-deletion (indel) variant in exon 26 of the TRPM6 gene, c.3693-3699del GCAAGAG ins CTGCTGTTGACATCTGCT, p.L1231Ffs*36. Segregation analysis revealed the TRPM6 heterozygous variant in both parents. Patients with biallelic TRPM6 pathogenic variants typically exhibit hypomagnesemia with secondary hypocalcemia and present with neurologic manifestations including seizures. In some patients, this is also complicated by chronic diarrhea and failure to thrive. Long-term complications are rare and most of the patients show a good prognosis with supplemental magnesium therapy.

The Impact of Oral Sodium Chloride Supplementation on Thrive and the Intestinal Microbiome in Neonates With Small Bowel Ostomies: A Prospective Cohort Study.

Background: Infants with ileostomies often suffer from sodium depletion, ultimately leading to a failure to thrive. Moreover, early-infantile microbial dysbiosis may potentially aggravate weight faltering. Given that sodium supplementation has been used to restore weight gain and feeding practices largely determine infantile microbiota, the current study investigated the effect of sodium chloride (NaCl) on weight gain and intestinal microbiome in infants with jejuno- and ileostomies. Methods: A prospective cohort study including 24 neonates with enterostomies compared 19 subjects receiving oral NaCl (5.85%) to five subjects without supplementation with respect to postoperative changes in thrive and the intestinal microbiome. Results: Infants receiving NaCl after enterostomy-surgery showed vastly improved weight gain and an increased abundance of Lactobacillus in fecal samples, as compared to subjects without oral supplement who displayed decreasing percentiles for weight and did not reveal a higher abundance of probiotic strains within the ostomy effluent. Contrarily, Klebsiella was equally enriched in supplemented infants, reflecting a higher susceptibility for infections in preterm neonates. Discussion: Our findings support oral NaCl supplementation as a mainstay of postoperative treatment in infants with small bowel ostomies who are predisposed to suffer from a sodium depletion-associated failure to thrive. Not only does NaCl promote weight gain by increasing glucose resorption, but it also appears to induce microbial restoration by enhancing the abundance of health-promoting probiotic bacteria. This finding has an even greater significance when facing an elevated Klebsiella/Bifidobacteria (K/B) ratio, believed to represent an early-life microbial biomarker for development of allergic disease.

Megaloblastic anaemia in a 9-weeks old infant: A case report.

Megaloblastic anaemia due to vitamin B12 and folic acid deficiency is uncommon in infancy and rarely reported in infants below 3 months of age. We hereby report a case of megaloblastic anaemia in a 9-weeks old infant having fever from 7th week of life. Blood picture showed pancytopenia and diagnosis was confirmed on bone marrow biopsy and serum level of vitamins. Patient positively responded to vitamin B12 and folic acid supplementation. Infants with pancytopenia even younger than 2 months, should also be investigated for vitamin B12 and folate deficiency. Mother of the baby was not antenatally investigated for anaemia. Prompt antenatal diagnosis and treatment of mothers can reduce the incidence in the infants.

Undernutrition in children & critical windows of opportunity in Indian context.

It is intriguing to note that majority of the wasting among the under 5 yr in India is present at birth. The National Family Health Survey 4 (NFHS-4) data analysis shows 31.9 per cent wasting at birth, which is decreasing to 17.7 per cent in the under five children; clearly suggesting that any reduction in wasting should come from improvement in foetal growth. In addition, children with both severe wasting and severe stunting, in whom the risk of mortality increases many folds, are <1 per cent in almost all the States; and these are the children in whom special care is required under the community-based management of severe acute malnutrition. This article presents an overview of nutrition status in children, their antecedents, and the critical phases; especially, nutrition status before pregnancy that plays a crucial role in all the nutrition status indicators of children. More attention on the critical phases is crucial to maximize the benefits from national programmes.

Chylomicron retention disease: A rare cause of chronic diarrhea.

Chylomicron retention disease (CRD) is a rare autosomal recessive hereditary hypocholesterolemic disorder. The disease most frequently presents in infants and is characterized by a lipid malabsorption syndrome with steatorrhea, chronic diarrhea, and growth retardation. The disease is characterized by normal fasting serum triglyceride levels combined with the absence of apolipoprotein (apo) B48 and chylomicrons after a fat load. In this report, we describe the clinical, laboratory, and histological data as well as the molecular DNA analysis of a 12-month-old girl from Tunisia with CRD. The patient was treated with a low-fat diet and fat-soluble vitamin supplementation resulting in significant improvement.

Improper Use of a Plant-Based Vitamin C-Deficient Beverage Causes Scurvy in an Infant.

Scurvy is a rare disease in developed countries. Risk groups include children with restricted diets, mainly patients who are autistic or have cerebral palsy. Furthermore, consumption of plant-based beverages has increased in recent years, especially in developed countries. When plant-based beverages are the exclusive diet in the first year of life and not consumed as a supplement to formula or breastfeeding, it can result in severe nutritional problems. We report a case of scurvy after exclusive intake of almond beverages and almond flour from 2.5 to 11.0 months of life. The patient was referred for pathologic fractures of the femur, irritability, and failure to thrive. He had typical radiologic signs of scurvy, such as osteopenia, cortical thinning, Wimberger ring, Frankel line, fracture, and periosteal reaction. Moreover, his plasmatic vitamin C level was very low. The child was diagnosed with scurvy and was started on vitamin C replacement therapy at a dose of 300 mg per day. Over the following 3 months, his general condition, the pain in the legs, and the radiologic features improved; the plasmatic vitamin C level was normalized; and the child started walking. In summary, this case demonstrates that scurvy is a new and severe complication of improper use of almond drinks in the first year of life. Manufacturers should indicate that these beverages are inappropriate for infants who consume a vitamin C-deficient diet.

Parenteral Nutrition in Very Low Birth Weight Preterm Infants.

Parenteral nutrition (PN) must be initiated as soon as possible after delivery in very low birth weight (VLBW) preterm infants in order to prevent postnatal growth failure and improve neurodevelopmental outcome. When administered early, high levels of parenteral amino acids (AA) are well tolerated and prevent negative nitrogen balance. Although proteins are the driving force for growth, protein synthesis is energy-demanding. Intravenous lipid emulsions (ILE) constitute a good energy source because of their high energy density and provide essential fatty acids (FA) along with their long-chain polyunsaturated fatty acid (LC-PUFA) derivatives necessary for central nervous system and retinal development. Early supply of ILE is not associated with increased morbidity. No significant differences were found between ILE based on soybean oil only and mixed ILE containing soybean oil in combination with other fat sources, except for a reduction in the incidence of sepsis with non-pure soybean ILE, and possibly less PN-associated liver disease with mixed ILE containing some fish oil. In preterm infants glucose homeostasis is still immature in the first days of life and abnormalities of glucose homeostasis are common. VLBW infants may not tolerate high levels of glucose infusion without hyperglycemia. Administering lower levels of glucose infusion as part of full early PN seems more successful than insulin at this stage. Postpartum there is a transition period when the water and electrolyte balance may be severely disturbed and should be closely monitored. Avoiding fluid overload is critical for preventing respiratory and other morbidities.

Vitamin Supplementation in the Elderly.

Vitamin supplementation is fairly common among the elderly. Supplements are often used to prevent disease and improve health. In the United States, the use of dietary supplements has continued to increase over the last 30 years, and more than half of adults report using one or more dietary supplements. Epidemiologic evidence suggests that a diet rich in fruits and vegetables does have a protective effect on health. However, clinical trials on the use of vitamin supplements for promotion of health and prevention of disease have failed to demonstrate the strong associations seen in observational studies.

Byler disease: early natural history.

OBJECTIVES: Byler disease, originally described in Amish kindred, results from mutations in ATPase Class I Type 8b Member 1 (ATP8b1). Specific clinical reports of Amish Byler disease were last published 40 years ago. These investigations were directed at the present detailed clinical understanding of the early course of hepatic manifestations of Byler disease. METHODS: This study analyzed routine clinical practice and outcomes of children with Byler disease (defined by homozygous c.923G>T mutation in ATP8b1), who initially presented to Children's Hospital of Pittsburgh of UPMC between January 2007 and October 2014. Data were analyzed to the earlier of 24 months of age or partial external biliary diversion. RESULTS: Six children presented between 1 and 135 days of life: 2 presented with newborn direct hyperbilirubinemia, 2 had complications of coagulopathy, 1 had failure to thrive and rickets, and 1 sibling was identified by newborn genetic testing. Intensive fat-soluble vitamin supplementation was required to prevent insufficiencies in vitamins D, E, and K. Hyperbilirubinemia was variable both over time and between children. Serum bile acid levels were elevated, whereas γ-glutamyltranspeptidase levels were low normal. Scratching behavior (pruritus) was intractable in 4 of 6 children with onset between 6 and 12 months of age. Features of portal hypertension were not observed. Partial external biliary diversion was used during the second year of life in 4 children. CONCLUSIONS: Detailed analysis of Byler disease revealed varied disease presentation and course. Nutritional issues and pruritus dominated the clinical picture in the first 2 years of life.

Growth failure and nutrition considerations in chronic childhood wasting diseases.

Growth failure is a common problem in many children with chronic diseases. This article is an overview of the most common causes of growth failure/growth retardation that affect children with a number of chronic diseases. We also briefly review the nutrition considerations and treatment goals. Growth failure is multifactorial in children with chronic conditions, including patients with cystic fibrosis, chronic kidney disease, chronic liver disease, congenital heart disease, human immunodeficiency virus, inflammatory bowel disease, short bowel syndrome, and muscular dystrophies. Important contributory factors to growth failure include increased energy needs, increased energy loss, malabsorption, decreased energy intake, anorexia, pain, vomiting, intestinal obstruction, and inflammatory cytokines. Various metabolic and pathologic abnormalities that are characteristic of chronic diseases further lead to significant malnutrition and growth failure. In addition to treating disease-specific abnormalities, treatment should address the energy and protein deficits, including vitamin and mineral supplements to correct deficiencies, correct metabolic and endocrinologic abnormalities, and include long-term monitoring of weight and growth. Individualized, age-appropriate nutrition intervention will minimize the malnutrition and growth failure seen in children with chronic diseases.

Two cases of rickets presenting with poor growth, hypotonia, and respiratory problems.

Rickets is a rare disease in developed countries. In children, it is a disease which affects growing bone. Depending on the severity, it can present with a wide variety of symptoms. Because it is such a rare disease in developed countries, symptoms suggesting rickets are often not easily recognized. This can cause a delay in diagnosing and treating rickets. Often unnecessary and sometimes invasive investigations are performed. First leading clues to rickets on physical examination are poor growth, especially length, thickening of wrists, bow legs, and craniotabes. At further examination, special attention should be paid to osteopenia and cupping and fraying at the metaphyses on X-rays. Laboratory results suggestive for rickets are elevated alkaline phosphatase and disturbances in calcium and phosphate homeostasis. In this report, we present two cases presenting with poor growth, severe pain, and respiratory problems secondary to calcipenic rickets.

[Clinico-biological and immunohaematological profile of patients with ß-thalassemia in Tunisia: about 26 cases]. / Profil clinico-biologique et immunohématologique des patients atteints de ß-thalassémie en Tunisie : à propos de 26 cas.

AIM OF THE STUDY: To study the clinical and biological profile of ß-thalassemic patients in our region, reflecting the quality of their care. PATIENTS AND METHODS: A retrospective study (2010-2011) on 26 ß-thalassemic patients followed in the pediatrics service at CHU Farhat Hached Sousse, Tunisia. Epidemiological, clinical and biological data were collected from medical records and transfusion files of patients. The transfusion protocol adopted was to maintain a hemoglobin level>10g/dL by regular transfusions every 3-4 weeks. Iron chelation therapy, in order to maintain serum ferritin<1500ng/mL, was introduced when serum ferritin exceeded 800-1000ng/mL. RESULTS: The mean age of patients at diagnosis was 15 months. The clinical impact of anemia had resulted in failure to thrive in 54% of patients and facial dysmorphism in 23%. The average transfusion requirement was estimated at 311.02mL/kg/year with 6 cases of hyperconsumption. The immunohaematological monitoring showed the appearance of anti-RBC alloimmunization in one patient and 4 cases of autoimmunization. Poor adherence of chelation therapy was 62% and causing 5 cases of cardiac complications, 4 cases of liver injury and 14 cases of endocrine complications. CONCLUSION: Improving the therapeutic care of ß-thalassemic children requires better monitoring of transfusion recovery and improved adherence to chelation therapy.

Growth in children with congenital diaphragmatic hernia during the first year of life.

PURPOSE: Infants with congenital diaphragmatic hernia (CDH) have high rates of mortality and long-term morbidity, including poor growth and failure to thrive. The aim of this study was to describe growth patterns during the first year of life in infants with congenital diaphragmatic hernia in a non-ECMO cohort. METHODS: Medical records of infants with CDH admitted to our center between January 2005 and December 2011 were reviewed. Infants with anthropometric measurements at 3, 6 and 12months were included. Anthropometric measurements were obtained for the first year of life. Logistic regression analyses were performed to find predictive associations with failure to thrive (FTT). RESULT: Of the 45 survivors, 38 were seen twice (84%) and 24 (53%) were seen on three occasions to age 12months. Poor growth was observed with weight being most affected. FTT was present in 63% during the first six months of life. Days of mechanical ventilation were the only predictor of FTT. Besides poor weight gain, height and head circumference were also reduced. However, catch-up growth occurred during the second half of infancy and at age 12months failure to thrive had reduced by two thirds to 21%. CONCLUSIONS: Poor growth is a common early finding in CDH patients, which improves during infancy. This emphasizes the importance of close follow-up and aggressive nutritional management in CDH patients.

The problematic Soave cuff in Hirschsprung disease: manifestations and treatment.

PURPOSE: Following a Soave pull-through for Hirschsprung disease (HD), some children struggle with obstructive symptoms. We hypothesized that these symptoms could result from a functional obstruction of the pull through caused by the Soave cuff, and that cuff resection might improve bowel emptying. METHODS: We reviewed patients referred to our center from 2008 to 2012 with obstructive problems following a Soave pull-through for HD (CCHMC IRB # 2011-2019). Only patients with an obstructing Soave cuff were analyzed. Patients with other reasons for obstruction (anastomotic stricture, transition zone, aganglionic segment) were excluded. RESULTS: Thirty-six patients underwent reoperation at our center for obstructive symptoms after an initial Soave pull-through. Seventeen of these patients had a Soave cuff only as the potential source of obstruction. Pre-operative symptoms included enterocolitis (10), constipation (6), and failure to thrive (1). Nine patients (53%) required irrigations to manage distension or enterocolitis pre-operatively. 14/17 patients (82%) had a palpable cuff on rectal exam. Eight patients (47%) had radiographic evidence of a cuff demonstrated by distal narrowing (4) or a prominent presacral space (4). Four children (23%) underwent excision of the cuff only. Thirteen (76%) had removal of the cuff and proximally dilated colon [(average length 7.2cm) (12 performed transanally, and five needed laparotomy as well.)] Post-operatively, episodes of enterocolitis were reduced to zero, and need for irrigation to treat distension was reduced by 50%. Nine patients have voluntary bowel movements, and five are clean on enemas. 3/6 patients with pre-operative constipation or impaction now empty without enemas. (Follow up 1-17months, mean 7months.) CONCLUSIONS: Recurrent enterocolitis, constipation, or failure to thrive can indicate a functional obstruction due to a Soave cuff when no other pathologic cause exists. Physical exam or contrast enema can identify a problematic cuff. Reoperation with cuff resection can dramatically improve bowel emptying.

Gitelman syndrome as a cause of psychomotor retardation in a toddler.

INTRODUCTION: Gitelman syndrome (GS) is a very rare autosomal recessive tubulopathy due to loss-of-function or mutation in solute carrier family12, member 3 gene (SLC12A3 gene) encoding thiazide-sensitive NaCl co-transporter in the distal convoluted tubule, leading to hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria and low-to-normal blood pressure. Clinical signs are mostly secondary to chronic hypokalemia and include dizziness, fatigue, constipation and weakness. Patients can also present with muscle cramps, tetany, fatigue and convulsions due to severe metabolic alkalosis or hypomagnesemia. Manifestations of GS are rarely apparent before the age of five, and the syndrome is usually diagnosed during adolescence or adulthood. Here we describe a case of GS presenting in infancy with hypokalemia and psychomotor retardation. CASE REPORT: We present an 18-month-old boy who presented with psychomotor retardation and failure to thrive. Investigations revealed hypokalemia at 2.7 mmol/L, metabolic alkalosis, hypocalciuria and normal serum magnesium level. The diagnoses of Barter syndrome (BS) and Gitelman syndrome (GS) were considered. Genetic studies confirmed the diagnosis of GS and three different mutations of in SLC12A3 gene were detected. Two mutations (c.2576T>C and c.2929C>Ty) were considered as causal ones, with the patient´s parents being the heterozygous carriers. Oral potassium supplementation resulted in normalisation of the hypokalemia and psychomotor improvement. CONCLUSION: We report a rare case of psychomotor retardation occurring at an early age in genetically confirmed GS. In spite of being a rare disorder, GS has to be considered in children with developmental delay and muscle weakness. With adequate treatment, GS patients have an excellent prognosis.

[Eat a citrus fruit, stay healthy--a case report of scurvy].

Scurvy is a disease that results from a vitamin C deficient diet. Since vitamin C is available in many food products, and especially in citrus fruits, the disease is rare in developed countries. Clinical manifestations of scurvy include general weakness, cutaneous and gum bleeding, pain in the lower limbs and inability to stand and walk (pseudo paralysis). The diagnosis of scurvy requires a high level of clinical suspicion, typical radiographic features and low Levels of vitamin C in the plasma. We report a case of a 7-year-old patient with a medical history of hydrocephalus, failure to thrive and severe psychomotor retardation due to complications of prematurity. On admission she had gum bleeding, severe anemia, pain in the lower limbs and refused to stand and walk. According to her parents, her diet was restricted, without vegetables or fruit consumption. Our investigation ruled out coagulopathy, malignancy and infection. Serum vitamin C levels were low and radiographic findings were consistent with the diagnosis of scurvy. The patient improved rapidly after the initiation of vitamin C supplements. Despite being rare, scurvy should be considered in the differential diagnosis of bleeding and pain in the lower limbs, especially in a malnourished patient.

Classic Bartter syndrome: a rare cause of failure to thrive in a child.

Bartter syndrome is a group of rare autosomal-recessive disorders caused by a defect in distal tubule transport of sodium and chloride. Blood gases and plasma electrolytes raise suspicion of this diagnosis and the definitive diagnosis is made by genetic study. Early treatment improves prognosis. The authors present the case of an 11-month-old child with early failure to thrive and severe regurgitation. Blood gases revealed hypochloraemic metabolic alkalosis, hyponatraemia and hypokalaemia. Blood pressure was normal and polyuria was documented. She began therapy with potassium chloride supplementation and indomethacin. There was clinical improvement and plasma potassium and bicarbonate normalised. The molecular study confirmed it was the classic form of Bartter syndrome. Despite being rare in clinical practice, which may lead to unnecessary medical investigation and diagnosis delay, in a child with failure to thrive, hypochloraemic metabolic alkalosis and hypokalaemia, this diagnosis must be considered.

[Pseudohypoaldosteronisme type I: a rare cause of failure to thrive]. / Une cause rare de stagnation pondérale à la naissance : le pseudohypoaldostéronisme de type I.

We report on a boy, born on term, presenting with a weight loss and a persistent failure to thrive after 10 days despite a normal behavior under bottle-feeding. The clinical examination was normal and biological assessment revealed hyponatremia with hyponatriuria, normal kaliemia and elevated aldosterone values, leading to type I pseudohypoaldosteronism diagnosis. Treatment with salt supplementation allowed growth improvement. The diagnosis was confirmed by the identification of a mutation in the mineralocorticoid receptor. This change was also found in several family members.

Nutritional and metabolic findings in patients with Prader-Willi syndrome diagnosed in early infancy.

OBJECTIVE: Early treatment (growth hormone and nutritional support) improves development in infants with Prader-Willi syndrome. This study aimed to evaluate the nutritional and metabolic condition of nine patients who were diagnosed and treated in early infancy. METHODS: Nine patients were hospitalized at the age of \xe2\u20ac\xa810 days to 11 months because of severe feeding difficulties, failure to thrive, or developmental delay. The diagnosis of Prader-Willi syndrome was confirmed by fluorescence in situ hybridization or other molecular genetic techniques. Nutritional and metabolic investigations including urinary organic acid analysis, blood amino acid, and acylcarnitine profiles were performed. RESULTS: The diagnosis was made at the mean age of 6.3 months. A deletion of the paternal gene in the 15q11-13 region was detected in all patients. Eight patients had ketosis, seven had malnutrition, five had hyperammonemia, three had liver dysfunction, three had low blood cholesterol level, and two had hypoglycemia. All patients had reduction of serum multiple amino acids and free carnitine. Significant arginine deficiency was found in all patients. Six patients had mildly elevated blood long-chain and very long-chain acylcarnitine. After supplementation with l-arginine, medium-chain fatty acids, l-carnitine, and vitamins, all patients responded with improvement of motor development and nutritional conditions. Four patients were almost caught up on physical and psychomotor development. CONCLUSIONS: Patients with Prader-Willi syndrome are in bad metabolic condition in the early period. Early diagnosis and individual nutritional interventions may improve the nutritional and developmental progress and decrease death rate in infancy.