The Italian External Quality Assessment Program for Cystic Fibrosis Sweat Chloride Test: Does Active Participation Improve the Quality?

(1) Background: Diagnostic testing for cystic fibrosis (CF) is based on a sweat chloride test (SCT) considering the appropriate signs and symptoms of the disease and results of a gene mutation analysis. In 2014, the Istituto Superiore di Sanità (ISS) established a pilot Italian external quality assessment program for CF SCT (Italian EQA-SCT), which is now a third party service carried out by the ISS. (2) Methods: The ongoing scheme is prospective, enrollment is voluntary, and the payment of a fee is required.

The Italian pilot external quality assessment program for cystic fibrosis sweat test.

Objectives: Sweat chloride test is the gold standard test for cystic fibrosis (CF) diagnosis. In 2014 the Istituto Superiore di Sanità established the Italian pilot external quality assessment program for CF sweat test (IEQA-ST).

Design And Methods: Ten laboratories, included among the 33 Italian CF Referral Centers, were selected and enrolled on the basis of their attitude to perform sweat test (ST) analysis by using methods recommended by the Italian Guidelines.

A neonatal case of 3-hydroxy-3-methylglutaric-coenzyme A lyase deficiency.

3-hydroxy-3-methylglutaric aciduria (OMIM 246450) is a rare autosomal recessive inborn of metabolism due to the deficiency of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase, an enzyme involved both in the ketogenic pathway and leucine catabolism. Acute decompensations present with lethargy, cianosis, hypotonia, vomiting and metabolic acidosis with hypoketotic hypoglycemia. We report the case of a 3 days male with sudden hypoglycemic crisis initially misdiagnosed as a sepsis.

Sudden unexpected infant death (SUDI) in a newborn due to medium chain acyl CoA dehydrogenase (MCAD) deficiency with an unusual severe genotype.

Medium chain acyl CoA dehydrogenase deficiency (MCAD) is the most common inborn error of fatty acid oxidation. This condition may lead to cellular energy shortage and cause severe clinical events such as hypoketotic hypoglycemia, Reye syndrome and sudden death. MCAD deficiency usually presents around three to six months of life, following catabolic stress as intercurrent infections or prolonged fasting, whilst neonatal-onset of the disease is quite rare.

Intermittent-relapsing pyruvate dehydrogenase complex deficiency: a case with clinical, biochemical, and neuroradiological reversibility.

Pyruvate dehydrogenase complex (PDHC) deficiency causes encephalomyopathies, of which there are four major categories: (1) neonatal encephalopathy with lactic acidosis; (2) an early infantile form, which (3) at times resembles Leigh syndrome; and (4) a later-onset form. Long-term clinical and radiological follow-up is still incompletely elucidated. We report a 12-year-old male with intermittent-relapsing PDHC deficiency who presented with three typical acute episodes of metabolic decompensation over 7 years.

Peroxisomal acyl-CoA-oxidase deficiency: two new cases.

We report on two new patients with straight-chain acyl-coenzyme A oxidase deficiency. Early onset hypotonia, seizures and psychomotor delay were observed in both cases. Plasma very-long-chain fatty acids were abnormal in both patients, whereas the plasma levels of phytanic acid, pristanic acid, the bile acid intermediates DHCA and THCA, and erythrocyte plasmalogen levels were normal.

Spectrum of MMACHC mutations in Italian and Portuguese patients with combined methylmalonic aciduria and homocystinuria, cblC type.

Methylmalonic aciduria (MMA) and homocystinuria, cblC type (MIM 277400) is the most frequent inborn error of vitamin B(12). The recent identification of the disease gene, MMACHC, has permitted preliminary genotype-phenotype correlations. We studied 24 Italian and 17 Portuguese patients with cblC defect to illustrate the spectrum of mutations in a southern European population and discuss the impact that mutation identification has on routine diagnostic procedures.

Severe epilepsy in X-linked creatine transporter defect (CRTR-D).

Disorders of creatine synthesis or its transporter resulting in neurological impairment with mental retardation and epilepsy have only been recognized in recent years. To date, the epileptic disorder observed in creatine transporter deficiency (CRTR-D) has been described as a mild phenotype with infrequent seizures and favorable response to common antiepileptic drugs. We report on a 5 year-old boy with known speech delay who presented with severe and refractory epilepsy.

Effect of carnitine supplementation on lipid profile and anemia in children on chronic dialysis.

We prospectively evaluated the effects of L-carnitine supplementation on plasma free carnitine (FC) levels, serum lipid profile, and erythropoietin (rhEPO) requirement in 24 children treated with peritoneal dialysis (PD; n=16) or hemodialysis (HD; n=8). The study was divided into a 3-month observation period, and a 3-month treatment period during which patients received 20 mg/kg per day of L-carnitine given orally. Clinical, biochemical, and hematological data were collected every 3 months.

A case of ethylmalonic encephalopathy with atypical clinical and biochemical presentation.

A child is reported presenting with a clinical picture suggestive of genetic connective tissue disorders (vascular fragility, articular hyperlaxity, delayed motor development, and normal cognitive development), an absence of pathological ethylmalonic acid excretion during inter-critical phases and a homozygous R163W mutation in the ETHE1 gene. This case suggests that ethylmalonic aciduria is not a constant biochemical marker of ethylmalonic encephalopathy and that its normal excretion outside of metabolic decompensation episodes does not exclude this metabolic disease.

X-linked creatine transporter deficiency: clinical description of a patient with a novel SLC6A8 gene mutation.

Creatine transporter deficiency is an X-linked disorder characterized by mental retardation and language delay. The authors report a patient affected by creatine transport deficiency caused by a novel mutation in the SLC6A8 gene. Impairment in social interaction represents a consistent clinical finding in the few cases described to date and may be a diagnostic clue for creatine transporter deficiency in males affected by mental retardation, seizures, and language impairment.

The secretion of ibuprofen metabolites interferes with the capillary chromatography of urinary homovanillic acid and 4-hydroxy-3-methoxymandelic acid in neuroblastoma diagnosis.

Neuroblastoma is the most common extracranial solid tumor in children. Abnormal secretion of catecholamines in tissues and body fluids allows for the differential diagnosis of neuroblastoma from other neoplasms and its distinction from non-neoplastic inflammatory diseases. This is achieved by assaying homovanillic acid and 4-hydroxy-3-methoxymandelic acid, the catabolites of catecholamine metabolism.

Severe lactic acidosis due to thiamine deficiency in a patient with B-cell leukemia/lymphoma on total parenteral nutrition during high-dose methotrexate therapy.

An 11-month-old girl with B-cell leukemia/lymphoma developed profound lethargy due to severe lactic acidosis during chemotherapy and total parenteral nutrition (TPN). Initial treatment with NaHCO3 was ineffective. Treatment with a vitamin cocktail (OH-cobalamin, pyridoxine, thiamine, riboflavine, biotin, carnitine) at pharmacologic doses rapidly improved the child's clinical and laboratory status.

Characteristic acylcarnitine profiles in inherited defects of peroxisome biogenesis: a novel tool for screening diagnosis using tandem mass spectrometry.

Patients with inherited defects of peroxisomal metabolism, a class of diseases with marked clinical and genetic heterogeneity, show a characteristic phenotype in most cases with severe neurologic impairment, craniofacial abnormalities, and hepatic and kidney dysfunction. For the differential diagnosis of clinically suspected cases, a complex biochemical and genetic approach is required. Analysis of plasma very-long-chain fatty acids is a reliable screening method to detect most but not all peroxisomal disorders.

Early-onset cobalamin C/D deficiency: epilepsy and electroencephalographic features.

Purpose: To describe epilepsy and EEG findings in the early-onset cobalamin (Cbl) C/D deficiency, an inborn error of intracellular Cbl metabolism characterized by high plasma levels of methylmalonic acid, homocystine, and homocysteine.

Methods: Type and frequency of seizures were studied in 10 patients (six boys and four girls) who underwent waking and sleep EEG.

Results: Half of patients had seizures in the first year of life (either concurrent with the other symptoms of disease or some months after the onset of disease); seizures occurred after 2 years in the other half of patients.

Inborn errors of metabolism in the Italian pediatric population: a national retrospective survey.

Objective: To estimate at the national level the overall and disease-specific incidence of inborn errors of metabolism not mass screened at birth.

Study Design: Prospective nonconcurrent study (1985-1997) on patients 0 to 17 years of age, diagnosed in 23 Italian pediatric reference centers.

Results: Cases (n = 1935) were recruited representing an incidence of 1:3707 live births for approximately 200 diseases.