Neutropenia and Increased Mean Corpuscular Volume (MCV) With Abnormal Neurologic Findings: A Case of Cobalamin D Deficiency.

BACKGROUND: Disorders of intracellular cobalamin (Cbl) metabolism are classified from A to J according to biochemical phenotype, and genetic and complementation analyses. CblD-deficient patients present with developmental, hematologic, neurologic, and metabolic findings. CLINICAL OBSERVATION: An 11-year-old boy presented with neutropenia, increased mean corpuscular volume, psychomotor retardation, and seizures. His plasma total homocysteine and urinary methylmalonic acid levels were elevated, and a homozygous nonsense mutation [p. R250X (c.748C>T] leading to premature termination of translation was identified in the MMADHC gene, which was compatible with CblD defect. CONCLUSION: In the presence of increased mean corpuscular volume and other hematologic manifestations, such as leukopenia, thrombocytopenia, and megaloblastic anemia, with severe nonspecific or mild neurologic symptoms, Cbl synthesis defects should be considered.

Long-term efficacy of lipoprotein apheresis in the management of familial hypercholesterolaemia: Application of two different apheresis techniques in childhood.

Lipoprotein apheresis is used to treat patients with familial hypercholesterolemia (FH). The aim of the present study is to clarify the lipoprotein apheresis procedure performed by cascade filtration (CF) or double filtration plasmapheresis (DFPP) on pediatric patients in terms of side effects, laboratory results and cardiovascular follow-up. Data of ten pediatric patients were analyzed retrospectively. The average age of the patients was 12.1 ± 3.4 years. Percentage of long term reduction of low density lipoprotein cholesterol was 62.35 ± 7.19% (n = 3) for CF and 63.66 ± 6.63% (n = 3) for CF plus DFPP, 64.79 ± 8.29% (n = 7) for DFPP. Cardiovascular disease was not detected in thirty percent of the patients. Lesions remained stable in fifty percent of patients with heart valve lesions. Valvular lesions worsened in twenty percent of patients. Lipoprotein apheresis can be used effectively and successfully in pediatric patients as well as adults for homozygous FH.

Tyrosinemia type II: Novel mutations in TAT in a boy with unusual presentation.

Tyrosinemia type II is a rare autosomal recessive disorder caused by deficiency of tyrosine aminotransferase (TAT). It may occur with ocular and cutaneous symptoms with or without mental retardation, but epileptic seizure is a rare presentation of this disease. Herein we report the clinical, biochemical and genetic features of a 4-year-old boy who presented with afebrile seizure and photophobia. Genomic DNA was obtained from peripheral blood leukocytes from the whole family. Sequencing analysis was performed using the MiSeq next-generation sequencing platform. Sequencing of TAT indicated two new homozygous mutations p.L312P (c.935T>C) and p.T408M (c.1223C>T) for the proband and his asymptomatic sister. During a 2 year follow-up period, the patient had overall poor compliance with protein-restricted diet, but his asymptomatic sister had good compliance with the diet. Cognitive function of the patient worsened steadily, but his asymptomatic sister maintained normal mental status. Tyrosinemia type II should be considered in the differential diagnosis of children presenting with epileptic seizure and photophobia; furthermore, early diagnosis and protein-restricted regimen are important to reduce the risk of long-term complications of tyrosinemia type II such as mental disability.

Evaluation of micronutrient levels in children and adolescents with obesity and their correlation with the components of metabolic syndrome.

BACKGROUND: Obesity is a significant public health problem worldwide. Vitamin deficiencies, developing due to monotype nutrition, are more likely to be observed in patients than healthy children. The present study evaluates vitamin and micronutrient levels in children and adolescents with obesity and metabolic syndrome compared to healthy controls. METHODS: The study included 73 patients with obesity, 64 patients with metabolic syndrome and 71 healthy children (control group) aged 10 to 16 years. Physical examinations were performed, and waist circumference and systolic blood pressure measurements were recorded. Fasting blood glucose, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, insulin, vitamin A, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, folic acid and free carnitine levels were analyzed. The homeostatic model of assessment-insulin resistance (HOMA-IR) index was calculated and recorded. RESULTS: The mean age of all patients was 11.9±2.6 years. The serum insulin level and HOMA-IR index were found to be significantly higher in the obesity and metabolic syndrome groups. No significant difference was found between the groups in terms of vitamin A, vitamin B6 and free carnitine levels. Significantly decreased vitamin E, vitamin B2, vitamin B12 and folic acid and increased vitamin B1 levels were observed in the obesity and metabolic syndrome groups. CONCLUSIONS: Compared to healthy children, children with obesity and metabolic syndrome may have varying degrees of micronutrient and vitamin deficiency due to poor and unbalanced eating habits. These deficiencies should also be considered in the treatment and follow-up of obesity and metabolic syndrome.

Novel MTTP Gene Mutation in a Case of Abetalipoproteinemia with Central Hypothyroidism

Abetalipoproteinaemia (ABL) is an autosomal recessive disorder characterized by very low plasma concentrations of total cholesterol and triglyceride (TG). It results from mutations in the gene encoding microsomal TG transfer protein (MTTP). A nine-month-old girl was admitted to hospital because of fever, cough, diarrhea and failure to thrive. She had low cholesterol and TG levels according to her age. The peripheral blood smear revealed acanthocytosis. Thyroid function test showed central hypothyroidism. Cranial magnetic resonance imaging revealed the retardation of myelination and pituitary gland height was 1.7 mm. A homozygous novel mutation [c.506A>T (p.D169V)] was detected in the MTTP gene. Vitamins A, D, E, and K and levothyroxine were started. The coexistence of ABL and central hypothyroidism has not previously been reported. A homozygous novel mutation [c.506A>T (p.D169V)] was detected in the MTTP gene.

Efficacy and safety of Saccharomyces boulardii in amebiasis-associated diarrhea in children.

The efficacy and safety of adding Saccharomyces boulardii to antibiotic treatment for amebiasis-associated acute diarrhea in children were assessed in this study. Forty-five children in Group I received only metronidazole per oral for 10 days while 40 patients in Group II received S. boulardii in addition to the same medication. The major outcomes investigated were duration of acute and bloody diarrhea, frequency and consistency of stools, resolution time of the symptoms, and the tolerance and side effects of the treatment regimens. The median duration of acute diarrhea was 5 (1-10) days in Group I and 4.5 (1-10) days in Group II (p=0.965). The median number of stools on follow-up and duration of bloody diarrhea, fever, abdominal pain and vomiting were similar in the two groups. S. boulardii was well tolerated by the children and no side effects were recorded. Addition of S. boulardii to antibiotic treatment of amebiasis-associated acute diarrhea in children does not seem to be more effective than metronidazole treatment alone.

Arthropathy-like findings and a carpal tunnel syndrome as the presenting features of Scheie syndrome: Three cases from the same family.

Gökay S, Kardas F, Kendirci M, Sözeri B. Arthropathy-like findings and a carpal tunnel syndrome as the presenting features of Scheie syndrome: Three cases from the same family. Turk J Pediatr 2018; 60: 344-347. Mucopolysaccharidosis (MPS) type I is a rare autosomal recessive disease caused by a deficiency of the lysosomal enzyme α-L-iduronidase. MPS I is divided into three subtypes based on the severity of symptoms: Hurler, Hurler-Scheie, and Scheie syndrome (severe, intermediate, and mild forms, respectively). Musculoskeletal involvement may be the only presenting sign in the patients with Scheie syndrome. We have reviewed three cases with prominent features of carpal tunnel syndrome (CTS) at the onset of their disease. Diagnosis was delayed in almost all cases (range 16-19 years). During one year of follow-up period, alleviations of the pain in the hands of patients were observed after enzyme replacement therapy. MPS type I should be considered in the differential diagnosis of the patients with CTS in the first and second decades of life, particularly with stiffness of the fingers and difficulty using the hands without an inflammatory component. An increased awareness of the disease may contribute to more accurate diagnosis, and patients may benefit from early intervention.

Glutaric Acidemia Type 1: A Case of Infantile Stroke.

BACKGROUND: Glutaric acidemia Type 1 (GA-1) is an autosomal recessively inherited metabolic disorder which is associated with GCDH gene mutations which alters the glutaryl-CoA dehydrogenase, an enzyme playing role in the catabolic pathways of the amino acids lysine, hydroxylysine, and tryptophan. Clinical findings are often encephalopathic crises, dystonia, and extrapyramidal symptoms. CASE REPORT: A 9-month-old male infant referred to our department with focal tonic-clonic seizures during rotavirus infection and acute infarcts in MRI. Clinical manifestation, MRI findings, and metabolic investigations directed thoughts towards GA-I. Molecular genetic testing revealed a homozygous c.572T>C (p.M191T) mutation in GCDH gene which confirmed the diagnosis. Application of protein restricted diet, carnitine and riboflavin supplementations prevented the progression of Magnetic Resonance Imaging (MRI) and clinical pathologic findings during the 1 year of follow-up period. CONCLUSION: This case is of great importance since it shows possibility of infantile stroke in GA-1, significance of early diagnosis and phenotypic variability of disease.

The outcome of seven patients with hereditary tyrosinemia type 1.

BACKGROUND: Hereditary tyrosinemia type 1 (HT1) is a rare, inborn error of tyrosine metabolism. It is a fatal disorder without treatment. Early treatment may prevent acute liver failure, renal dysfunction, liver cirrhosis, hepatocellular carcinoma (HCC) and improves survival. The aim of the present study is to describe the clinical, biochemical, imaging and follow-up of seven patients with HT1 and to define the consequences of the late and interrupted treatment. METHODS: A retrospective study was carried out with seven HT1 patients. RESULTS: The median age at onset of clinical symptoms was 11.2 months (range, 3-28 months) and the median age at diagnosis was 22 months (range, 6-58 months). Liver enzymes and coagulation parameters were back to normal in all symptomatic patients in about 2 weeks. Alfa-fetoprotein (AFP) levels were normalized within the first year of therapy. Hypoechoic nodule formation was detected in two of the seven patients despite drug treatment without an increase of AFP and any dysplastic changes in the biopsies. One patient died due to metastatic HCC because of the late diagnosis and the poor compliance of the follow-up. CONCLUSIONS: This study showed once again that adherence to the treatment and a follow-up schedule of the patients are very important. Also it should not be forgotten that nodule formation can occur despite nitisinone treatment without an increase of AFP. Despite nitisinone treatment, HT1 patients still carry the risk of HCC. HCC must be detected before metastasis to other organs otherwise, patients may lose the chance for liver transplantation.