A Case of Glycogen Storage Disease Type 1a Mimicking Familial Chylomicronemia Syndrome.

Glycogen storage disease type 1a (GSD1a) is an autosomal recessively inherited inborn error of metabolism caused by a mutation in the G6PC gene, which encodes the catalytic subunit of glucose-6-phosphatase-α (G6Pase-α) enzyme. This enzyme plays a role in the final step of gluconeogenesis and glycogenolysis. Patients carrying GSD1a show growth retardation, hypoglycemia, hepatomegaly, hepatic steatosis, hyperlipidemia, hyperuricemia and lactic acidemia. Long-term symptoms include gouty arthritis and uric acid stones, osteoporosis, renal failure, intestinal impairment, cirrhosis and hepatic adenomas, and eventually, hepatocellular carcinoma. Hyperlipidemia is the indicator of poor metabolic control in GSD1a. Patients with variable levels of triglycerides (TGs) have been reported in the literature. We present a case of GSD1a that presented with severe hypertriglyceridemia (HTG) mimicking familial chylomicronemia syndrome.

A 7-year-old Boy with Hand Tremors and a Novel Mutation for L-2-hydroxyglutaric Aciduria.

L-2-hydroxyglutaric aciduria (L2HGA), which is a rare autosomal recessive metabolic disorder caused by mutations in the encoding L2HGDH gene. Neurological symptoms are the main predominant clinical signs. The distinctive feature is the specific multifocal lesion of the white matter detected on magnetic resonance imaging (MRI). A 7-year-old male patient of Turkish origin was admitted to the hospital because of hand tremors. Physical examination revealed macrocephaly, intention tremors, walking disability and ataxic gait. Urine organic acid analysis showed increased excretion of L-2-hydroxyglutaric acid (L2HG acid). Analysis of the L2HGDH gene revealed a novel homozygous c.368A>G, p. (Tyr123Cys) mutation. L-2-hydroxyglutaric aciduria is a cerebral organic aciduria that may lead to various neurological complications. Early recognition of symptoms of L2HGA is important for initiation of supportive therapy that may slow down the progression of the disease.

Phenotype-genotype correlations in patients with Marinesco-Sjögren syndrome.

Marinesco-Sjögren syndrome (MSS; MIM 248800) is an autosomal recessive disorder characterized by congenital cerebellar ataxia, early cataracts, developmental delay, myopathy and short stature. Alterations in the gene SIL1 cause MSS in some patients with typical findings. In this study, molecular investigations including sequencing of the SIL1 gene, western blotting and microscopic investigations in fibroblast cultures were carried out in a cohort of 15 patients from 14 unrelated families, including the large, inbred family reported by Superneau et al., having the clinical features of MSS to provide insights into the pathophysiology of the disorder. A total of seven different mutations were found in eight of the patients from seven families. The mutations caused loss of the BIP-associated protein (BAP) protein in four patients by western blot. Novel clinical features such as dental abnormalities, iris coloboma, eczema and hormonal abnormalities were noticed in some patients, but there was no clear way to distinguish those with and without SIL1 mutations. Cultured fibroblasts contained numerous cytoplasmic inclusion bodies, similar to those identified in the brain of the whoozy mouse in five unrelated patients, three with and two without SIL1 mutations, suggesting some SIL1 negative patients share a common cellular pathogenesis with those who are SIL1 positive.

An infantile case of Zellweger syndrome presented with Kabuki-like phenotype.

Zellweger syndrome is a peroxisomal disorder resulting from the mutations in PEX genes generally presenting in the neonatal period with profound hypotonia seizures, inability to feed, liver cysts with hepatic dysfunction, chondrodysplasia punctata. Kabuki make-up syndrome is a multiple congenital anomalies and mental retardation syndrome with characteristic facial appearance, skeletal abnormalities, dermatoglyphic abnormalities, mental retardation and short stature. Abnormal liver functions and some atypical findings were also reported in some patients with Kabuki syndrome. In this report a case with late onset Zellweger syndrome who had some phenotypical findings which are also seen in Kabuki Syndrome will be presented. The inclusion of Zellweger syndrome into the differential diagnosis of the patients with Kabuki-like phenotype in addition to abnormal liver functions is emphasized.

Effect of enteral and parenteral nutrition on growth parameters of hospitalized Turkish children.

This study was conducted to investigate growth and the complications in the hospitalized pediatric patients receiving either enteral (n = 26) or parenteral (n = 15) nutrition. Anthropometric measures as well as the results of biochemical analyses and complete blood counts were recorded. Weight, height and weight for height were expressed in z scores. The improvement in z scores for the 26 children receiving enteral nutrition in weight for age (P = 0.001), height for age (P = 0.002) and weight for height (P = 0.008) were all statistically significant. There were also significant correlations between the changes in weight for age (r2 = 0.15, P = 0.0049) and height for age (r2 = 0.64 and P = 0.0001) z scores and the time for follow up. Corresponding z scores in the parenteral nutrition group were not statistically significant. This study indicated that enteral nutrition provides significant improvement not only in weight but also height of sick hospitalized pediatric patients.

Autoimmune polyglandular syndrome type I. A case report.

Autoimmune polyglandular syndrome (APS) type I is a disorder that consists of three primary diseases: hypoparathyroidism (HPT), adrenocortical insufficiency (ACI) and chronic mucocutaneous candidiasis. Several other disorders may be associated. The diagnosis of APS type I was made in a 16-year-old patient with HPT, Hashimato's thyroiditis and ACI in our department. She has been observed for more than four years for other possible endocrine and non-endocrine disorders.

SRD5A3-CDG: a patient with a novel mutation.

Congenital disorders of glycosylation (CDG) are genetic diseases with an extremely broad spectrum of clinical presentations due to defective glycosylation of glycoproteins and glycolipids. Some 45 CDG types have been reported since the first clinical description in 1980. Protein glycosylation disorders are defects in protein N- and/or O-glycosylation. Dolichol phosphate is the carrier of the N-glycan during their assembly first at the outside and subsequently at the inside of the endoplasmic reticulum (ER) membrane, and hence is a key molecule in protein glycosylation. Recently, defects have been identified in the last three steps of the dolichol phosphate biosynthesis: dolicholkinase deficiency (DK1-CDG), steroid 5alpha-reductase type 3 deficiency (SRD5A3-CDG), and dehydrodolichyl diphosphate synthase deficiency (DHDDS-CDG). We report on a patient with SRD5A3-CDG carrying a novel (homozygous) mutation. The diagnostic features of this novel inborn error of glycosylation are psychomotor retardation, nystagmus, visual impairment due to variable eye malformations, cerebellar abnormalities/ataxia, and often ichthyosiform skin lesions.

Plasma leptin levels of large for gestational age and small for gestational age infants.

The hormone leptin produced in the adipose tissue is involved in the regulation of body weight. This study investigates whether plasma leptin levels are related to an infant's birthweight, and whether the levels change with feeding. We measured plasma leptin levels from infants who were large for gestational age (n = 21), small for gestational age (n = 21), and appropriate for gestational age (n = 20). Two blood samples were collected before and after breastfeeding from each infant and plasma leptin concentrations were determined by radioimmunoassay. Leptin concentration was found to be increased in large for gestational age infants and to be decreased in small for gestational age infants compared with the level in appropriate for gestational age infants. There was a positive correlation between plasma leptin levels and both the infants' birthweights and the body mass indexes. Plasma leptin concentrations were found to be decreased during fasting and to be increased after feeding (p < 0.01). It is concluded that the plasma leptin levels correlate with the size of adipose tissue mass and are related to the nutritional status.

Cerebrospinal fluid and serum nitric oxide levels in asphyxiated newborns.

Hypoxic-ischemic encephalopathy (HIE) is the result of a chain of events caused mainly by cytokines and nitric oxide (NO) release, which is later on followed by free oxygen radical injury. To investigate NO involvement in asphyxiated newborns, serum and cerebrospinal fluid (CSF) values of NO levels in 17 neonates with HIE were detected. Infants at or above 37 weeks of gestation were classified to have mild, moderate and severe HIE due to Sarnat and Sarnat. Samples obtained between 24 and 72 h of life were immediately frozen at -70 degrees C till the time of measurement by Sievers NOA. Five patients had mild, 6 patients had moderate and 6 patients had severe HIE, 4 in the severe HIE group also had multisystem involvement. The CSF NO levels were significantly higher in moderate and severe HIE groups compared to the mild HIE group (p = 0.028 and p = 0.018 respectively). Our results show that NO level increases in CSF with the severity of HIE between 24 and 72 h following asphyxia. According to the animal work, this is the time period where inducible NO synthase gets activated and could cause neurotoxicity, which might perhaps be prevented by interventions.

Serum carnitine levels in newborns with perinatal asphyxia and relation to neurologic prognosis.

Neonatal hypoxic encephalopathy is one of the major causes of permanent neurological sequel. This study was conducted to investigate serum total, free and acylcarnitine levels in asphyxiated newborns with or without encephalopathy. Serum total, free and acylcarnitine levels were investigated in 21 newborns with and seven asphyxiated newborns without signs of encephalopathy. The newborns with encephalopathy were further divided into grade 1, 2 and 3 encephalopathy groups. Serum total and acylcarnitine concentrations of the whole encephalopathy group were significantly lower than the non-encephalopathy group (p = 0.042 for both). Serum total and acylcarnitine concentrations of grade 3 encephalopathy group were significantly lower than the non-encephalopathy group (p = 0.014 and p = 0.040, respectively). No significant differences were noticed for free carnitine levels. Total carnitine levels were positively correlated with birth weight and 10th minute apgar score, whereas acylcarnitine levels were found to correlate with cord blood pH and free carnitine levels with birth weight. Cord blood pH, and total carnitine levels were found to be the most significant determinants of the neurological outcome at one year of age. It was emphasized that carnitine deficiency could occur in severely affected asphyxiated newborns and it is related to the outcome at one year of age.