Panagiota Triantafyllou

Niemann-pick type C disease associated with peripheral neuropathy

Niemann-Pick type C disease is an autosomal-recessive, inherited neurovisceral lipid storage disorder. This disease results from either protein NPC1 or HE1 deficiency, which leads to cholesterol metabolism disturbance and is characterized by early hepatosplenomegaly and progressive ataxia, dystonia, cataplexy, dysarthria, and dementia. We describe a 3 1/2-year-old patient with Niemann-Pick type C disease, who presented with regression in both cognitive and motor domains. Almost 10 months before admission to the hospital, the child developed progressive speech and behavioral changes, as well as gait disturbances with frequent falls. The examination demonstrated hepatosplenomegaly, ataxia, and vertical gaze palsy. Nerve conduction velocities demonstrated mild demyelinating peripheral neuropathy. Bone marrow examination revealed foam cells, and cholesterol esterification studies found massive accumulation of unesterified cholesterol and very low intracellular esterification of exogenous lipoprotein-derived cholesterol. These results indicate Niemann-Pick type C disease. Peripheral neuropathy is a rare complication in patients with Niemann-Pick type C disease, which certainly contributes to their neurologic deterioration.

Thelarche variant in a girl with Angelman syndrome

A case of Angelman syndrome (AS) with thelarche variant in a 4.5-year-old girl is presented. Clinical suspicion of AS was raised at the age of 15 months when she presented with mental retardation and epilepsy, absence of speech, ataxic gait with jerky movements, hyperactivity and paroxysmal episodes of laughter. Moreover, she had facial dysmorphic features such as microbrachycephaly, mid-facial hypoplasia, macrostomia and prominent mandible. Dinucleotide repeat polymorphism (DNRP) analysis, identified absence of maternal alleles at D15S543, D15S113 and GABRB3 loci, findings consistent with AS. Studies on CYP19 locus (outside the 15q11-13 region) revealed the presence of two different alleles, thus excluding the possibility of paternal isodisomy of chromosome 15 in this patient. Breast development at the age of 4.5 years, accompanied by accelerated growth velocity and bone age suggested the diagnosis of variant thelarche. This is the second case of AS with sexual precocity reported and whether this combination is a coincidence or not remains to be clarified.

Transient generalized glucocorticoid hypersensitivity.

Transient generalized glucocorticoid hypersensitivity is a rare disorder characterized by increased tissue sensitivity to glucocorticoids and compensatory hypo‐activation of the hypothalamic–pituitary–adrenal axis. The condition itself and the underlying molecular mechanisms have not been elucidated.

Glucose Levels Before the Onset of Asparaginase Predicts Transient Hyperglycemia in Children With Acute Lymphoblastic Leukemia

Transient hyperglycemia (TH) represents an acknowledged adverse event that occurs during treatment in children with acute lymphoblastic leukemia (ALL) and has recently been associated with an increased risk for developing metabolic disturbances in future life. Our aim was to estimate the incidence of TH and to identify risk factors, thus serving as markers for identifying candidates for prevention interventions.

Multiple Endocrine Disorders Associated With Adrenomyeloneuropathy and a Novel Mutation of the ABCD1 Gene

INTRODUCTION X-linked adrenomyeloneuropathy (X-AMN) is a genetic disorder that primarily affects the adrenal cortex and the nervous system. The disease shows a wide range of phenotypic expression, age of onset, and rate of progression. PATIENT DESCRIPTION We present a thalassemic 23-year-old man with X-AMN and multiple endocrine disorders. At age 2 years, he was diagnosed with thalassaemia intermedia, and he was receiving occasional blood transfusions and maintaining an adequate hemoglobin level without signs of extramedullar hematopoiesis or hemosiderosis. During adolescence, he was diagnosed with growth hormone deficiency, primary hypothyroidism, and primary adrenal insufficiency. In his early 20s he demonstrated progressive tetraparesis, and the diagnosis of X-AMN was confirmed by DNA analysis of the ABCD1 gene. CONCLUSION This patient expands the phenotype X-AMN by adding growth hormone deficiency and hypothyroidism.

Early-onset diabetes mellitus and neurodevelopmental retardation: the first Greek case of Wolcott-Rallison syndrome

Abstract Wolcott-Rallison syndrome (WRS) is a very rare genetic disorder, which is transmitted by autosomal recessive inheritance and results from mutations in the gene encoding the eukaryotic initiation factor 2-α kinase-3 (EIF2AK3). The cardinal features of the syndrome include early-onset insulin-dependent diabetes mellitus, multiple epiphyseal dysplasia, and growth retardation. We present the case of a 13-year-old Greek boy with a known history of infancy-onset diabetes mellitus and was found to have WRS at the age of 4 years. He presented with acute liver and renal insufficiency in addition to skeletal dysplasia and neurodevelopmental retardation. The clinical suspicion of WRS was confirmed by molecular analysis of the EIF2AK3 gene. The patient was found to be a compound heterozygote with two different novel mutations (c.2776C>T, p.R902X and c.3038A>G, p.Y989C). The current patient is one of the longer survivors.

Level of Internet use among Greek adolescents with type 1 diabetes

Abstract Background Compulsive Internet use has emerged as a contemporary addictive behavior. Our aim was to investigate the reasons for Greek adolescents with type 1 diabetes mellitus (T1DM) and their families to use the Internet and additionally to investigate the level of Internet use and its associations to demographic, socio-economic parameters and glycemic control. Methods Patients with T1DM, aged >12 years and their parents were recruited during their regular visits to the Pediatric Diabetes Clinic. A similar group of healthy children, age- and sex-matched served as a control group. All participants were asked to fill out the Greek translated version of the Internet Addiction Test (IAT). Caregivers of patients with T1DM were asked to complete a second questionnaire consisting of questions regarding demographic and socio-economic data of the family and data concerning disease management. Results Thirty-five patients with T1DM (mean decimal age of 14.95 ± 1.90 years) and 35 controls participated in the study. Nine patients were on an insulin pump whereas the rest were on multiple daily injections. The mean total score of the patients’ IAT questionnaires was significantly lower compared to the controls (26.26 ± 12.67 vs. 39.91 ± 18.55, p = 0.003). Controls were characterized as exhibiting moderate addictive behavior at a significantly higher percentage than patients (31.43% vs. 2.86%, p = 0.002). All patients on insulin pumps demonstrated normal Internet use. Mild addictive behavior was associated with a lower parental educational level. Finally, level of Internet use (IAT score) was positively associated to glycemic control (HbA1c value) with a correlation that was approaching significance (r = 0.315, p = 0.065). Conclusions Adolescents with T1DM and especially those on an insulin pump exhibit normal Internet use compared to their healthy peers. Time consumed on Internet correlates reversibly with glycemic control.

Growth hormone replacement therapy in Costello syndrome.

Costello syndrome (CS) is considered an overgrowth disorder given the macrosomia that is present at birth .However, shortly after birth the weight drops dramatically and the patients are usually referred for failure to thrive. Subsequently, affected patients develop the distinctive coarse facial appearance and are at risk for cardiac anomalies and solid tumor malignancies. Various endocrine disorders, although not very often, have been reported in patients with CS, including growth hormone deficiency, hypoglycemia, ACTH deficiency, cryptorchidism and hypothyroidism. We report a case of Costello syndrome with hypothyroidism, cryptorchidism and growth hormone deficiency and we evaluate the long-term safety and efficacy of growth hormone replacement therapy. The index patient is a paradigm of successful and safe treatment with growth hormone for almost 7 years. Since patients with CS are at increased risk for cardiac myopathy and tumor development they deserve close monitoring during treatment.

A girl with progressive fatigue and hyponatremia: question

Case summary A 9-year-oldgirl was admittedtohospitalduetoemesis,fatigue and lethargy. She is the only child of unrelated Caucasian parents. Her mother has recently been diagnosed with Crohn’s disease and diabetes mellitus type I. During the 3 months preceding admission, the child had three episodes of gastroenteritis-like illness with vomiting and lethargy; for the two of these episodes, she was admitted to hospital where hyponatraemia was determined. The patient was treated with intravenous fluids, and she quickly recovered. The current episode was the fourth one of emesis and had started 24 h prior to admission, with recurrent abdominal pain and no diarrhoea. On the day of admission she deteriorated and became lethargic. She was afebrile. The mother had noticed progressive fatigue and weakness during the last few months as well as aw eight loss of 5 kg.

A girl with progressive fatigue and hyponatremia: answer

1. During the last few months preceding admission, the patients mother noticed progressive fatigue and weakness as well as a craving for salt. Clinical examination revealed moderate hyperpigmentation, particularly at the elbows, knees, palmar creases and buccal mucosa. The patient’s mother noted that, contrary to previous years, the patient’s suntan had not faded, even by the middle of the fall. 2. Typical but not specific symptoms and hyperpigmentation suggested the diagnosis of adrenal insufficiency despite a normal plasma K concentration. 3. The patient was asked to perform an adrenocorticotropic hormone (ACTH) stimulation test 1 week after admission, when she was clinically and biochemically stable. This test revealed elevated ACTH (result 273 pg/ml, normal range 9–52 pg/ml) and very low cortisol levels (1.0 mg/dl before and 1 h after ACTH administration). The aldosterone level was low (0.8 ng/dl), but the renin level was in the normal range. The test for antibodies to the adrenals was negative. An abdominal ultrasound scan and magnetic resonance imaging revealed no pathology of the adrenals. These results are consistent with a diagnosis of Addison’s disease. The patient was subsequently treated with hydrocortisone (15 mg/m/day) and fludrocortisone (1 mg/day). She remained stable with normal Na and K levels and was discharged with guidelines on stress dose of hydrocortisone in the case of coincidental illness or surgery. She has been closely followed up and remains in good health at 6 months post-diagnosis.