Federica Ciani

Two novel genetic lesions and a common BH4-responsive mutation of the PAH gene in Italian patients with hyperphenylalaninemia

Hyperphenylalaninemia (HPA), due to a deficiency of phenylalanine hydroxylase (PAH) enzyme, is caused by mutations in the PAH gene. Molecular analysis in 23 Italian patients with PAH deficiency identified two novel (P281R, L287V) and 20 previously described genetic lesions in the PAH gene. The detection of the A403V amino acid substitution in combination with null mutations in patients with BH4-responsive PAH deficiency leads us to correlate it with BH4 responsiveness.

Neonatal onset of hyperornithinemia-hyperammonemia-homocitrullinuriasyndrome with favorable outcome

We report on a neonate with hyperammonemic coma in whom hyperornithinemia-hyperammonemia-homocitrullinuria syndrome was diagnosed. Appropriate treatment led to rapid clinical and metabolic improvement. The incorporation of 14C-ornithine on cultured fibroblasts confirmed the diagnosis. At the age of 18 months, the patient is in excellent clinical condition.

Fatal Malonyl CoA Decarboxylase Deficiency Due to Maternal Uniparental Isodisomy of the Telomeric End of Chromosome 16

Malonic aciduria is a rare autosomal recessive disorder caused by deficiency of malonyl‐CoA decarboxylase, encoded by the MLYCD gene.

Lethal late onset cblB methylmalonic aciduria.

Objective To alert the physicians to the possibility of a late-onset inborn error of metabolism in an apparently previously healthy patient with acute clinical presentation. Design Case report. Setting Pediatric unit and general intensive care unit Patient An apparently previously healthy 12-yr-old female presented acutely with vomiting, fever, bronchopneumonia, and progressive loss of consciousness associated with ketoacidosis, hyperglycemia, and hyperammonemia. She died 3 days later with a diagnosis of insulin-dependent diabetes mellitus. Interventions Intravenous hydration, glucose and insulin, mechanical ventilation. Measurements and Main Results Organic acid analysis on a postmortem sample of aqueous humor revealed high levels of methylmalonic acid. Enzymatic studies on cultured fibroblasts were consistent with the diagnosis of cblB methylmalonic aciduria. Conclusions The diagnosis of cblB methylmalonic aciduria was made in a postmortem patient who died with a misdiagnosis of insulin-dependent diabetes mellitus. Unclear biochemical findings and positive family history should strongly lead to suspicion of an inborn error of metabolism in an apparently previously healthy critically ill patient.

Genetic and biochemical approach to early prenatal diagnosis in a family with mut methylmalonic aciduria

Genetic and biochemical prenatal diagnosis was performed at 11 weeks of gestation in a family with a proband affected by mut methylmalonic aciduria (MMA) and homozygotes for the MUT gene c.643G>A (p.Gly215Ser) mutation. Both chorionic villus and amniotic fluid samples were used. The presence of high levels of methylmalonic acid and propionylcarnitine determined by gas chromatography/mass spectrometry and LC/MS/MS analysis, respectively, and the identification of the p.Gly215Ser at a homozygous level in foetal DNA allowed a certain, rapid and early diagnosis. To our knowledge, this is the first mut MMA prenatal diagnosis carried out by genetic and biochemical approach.

Two new mutations in children affected by partial biotinidase deficiency ascertained by newborn screening

Mutation analysis performed on DNA from 6 Italian patients with partial biotinidase deficiency ascertained by newborn screening allowed the identification of two new mutations, c1211C>T (T404I) and a single base deletion c594delC. All patients were compound heterozygous for the D444H amino acid substitution showing that this mutation is also common in Italian patients affected by partial biotinidase deficiency.

Fructose-1,6-Diphosphatase Deficiency Misdiagnosed as Reye Syndrome

can cause life-threatening hypoglycemic episodes with lactic acidosis and ketosis. In approximately half of cases, the disease presents in the neonatal period with hyperventilation, dyspnea, apneic episodes, tachycardia, irritability, lethargy, coma, muscular hypotonia, hepatomegaly, hypoglycemia, severe metabolic acidosis, and hyperlactacidemia.2 2 In infancy and early childhood, hypoglycemia is triggered by intercurrent infections, prolonged fasting, and vomiting.2 2

Electromyographic Alterations in Hyperphenylalaninemia due to Dihydropteridine Reductase Deficiency

The electroneurography and electromyography (EMG) were performed using a Viking II (Nicolet) electromyograph. Right peroneal and left median nerve motor conduction were recorded by surface electrodes, after the application of a supramaximal stimulus (duration: 0.2 ms; band width: 2Hz-lOkHz). A concentric needle electrode (20Hz-lOkHz) was used for the electromyographic recordings. The testing was performed at rest (3 different sites for 30 seconds each) and during voluntary or reflex (for 10 seconds) activity, in the anterior tibialis and deltoid muscles. Analysis of motor unit potentials was also performed in five insertions. Twenty potentials were analyzed by the automatic motor unit potentials analysis; the system extracts, identifies, and stores the motor units (maximum 42 samples), and then averages three motor units and calculates duration, amplitude, phases (number and percentage), and turns. Reflex activity was elicited in the anterior tibialis and deltoid muscles by tickling the sole of the foot and pinching the axilla respectively. Follow-up studies were performed at 2 months, 1 year, and 2 years after the first examination.