Chronic Diarrhea in L-Amino Acid Decarboxylase (AADC) Deficiency: A Prominent Clinical Finding Among a Series of Ten French Patients.

Aromatic L-amino acid decarboxylase (AADC) deficiency is an autosomal recessive inborn error of metabolism, affecting catecholamines and serotonin biosynthesis. Cardinal signs consist in psychomotor delay, hypotonia, oculogyric crises, dystonia, and extraneurological symptoms. PATIENTS AND METHODS: We present a retrospective descriptive multicentric study concerning ten French children with a biochemical and molecular confirmed diagnosis of AADC deficiency. RESULTS: Clinical presentation of most of our patients was consistent with the previous descriptions from the literature (hypotonia (nine children), autonomic signs (nine children), sleep disorders (eight children), oculogyric crises (eight children), motor disorders like hypertonia and involuntary movements (seven children)). We described however some phenotypic particularities. Two patients exhibited normal intellectual abilities (patients already described in the literature). We also underlined the importance of digestive symptoms like diarrhea, which occurred in five among the ten patients. We report in particular two children with chronic diarrhea, complicated by severe failure to thrive. Vanillactic acid (VLA) elevation in urines of one of these two patients led to suspect the diagnosis of AADC deficiency, as in two other patients from our population. CONCLUSION: Some symptoms like chronic diarrhea were atypical and have been poorly described in the literature up to now. Diagnosis of the AADC deficiency is sometimes difficult because of the phenotypic heterogeneity of the disease and VLA elevation in urines should suggest the diagnosis.

Phenotype and genotype in 101 males with X-linked creatine transporter deficiency.

BACKGROUND: Creatine transporter deficiency is a monogenic cause of X-linked intellectual disability. Since its first description in 2001 several case reports have been published but an overview of phenotype, genotype and phenotype--genotype correlation has been lacking. METHODS: We performed a retrospective study of clinical, biochemical and molecular genetic data of 101 males with X-linked creatine transporter deficiency from 85 families with a pathogenic mutation in the creatine transporter gene (SLC6A8). RESULTS AND CONCLUSIONS: Most patients developed moderate to severe intellectual disability; mild intellectual disability was rare in adult patients. Speech language development was especially delayed but almost a third of the patients were able to speak in sentences. Besides behavioural problems and seizures, mild to moderate motor dysfunction, including extrapyramidal movement abnormalities, and gastrointestinal problems were frequent clinical features. Urinary creatine to creatinine ratio proved to be a reliable screening method besides MR spectroscopy, molecular genetic testing and creatine uptake studies, allowing definition of diagnostic guidelines. A third of patients had a de novo mutation in the SLC6A8 gene. Mothers with an affected son with a de novo mutation should be counselled about a recurrence risk in further pregnancies due to the possibility of low level somatic or germline mosaicism. Missense mutations with residual activity might be associated with a milder phenotype and large deletions extending beyond the 3' end of the SLC6A8 gene with a more severe phenotype. Evaluation of the biochemical phenotype revealed unexpected high creatine levels in cerebrospinal fluid suggesting that the brain is able to synthesise creatine and that the cerebral creatine deficiency is caused by a defect in the reuptake of creatine within the neurones.

[Diagnosis and care of Wilson disease with neurological revelation]. / Maladie de Wilson, penser aux formes neurologiques chez l'enfant.

Wilson disease is an autosomal recessive disease that produces a copper accumulation in many organs, initially in the liver, progressing to liver cirrhosis, and in the brain, with different neurologic symptoms. Diagnosis is based on clinical, biochemical, and genetic tests. Different treatments based on chelating agents may help reduce the disease's spontaneous morbidity and mortality. We describe three patients who presented Wilson disease before 18 years of age, with initial neurologic symptoms between 1998 and 2010. After comparison with literature reports, their clinical symptoms, progression, and care allowed us to propose a treatment algorithm. Neurologic symptoms are present in 35% of the patients with Wilson disease such as dystonia, extrapyramidal syndrome, dysarthria, dysphagia, and psychiatric symptoms. The time to diagnosis remains too long and may account for the increased severity of the illness encountered and problems treating these patients. The first treatment choice must be triethylenetetramine, which causes fewer side effects of initial worsening of symptoms compared to D-penicillamine. Zinc therapy is the first treatment for asymptomatic patients or those on maintenance treatment. Finally, liver transplantation is a potential treatment even if the patient presents severe neurological disability because it may improve clinical symptoms. However, further research is warranted on this matter.

Severe neonatal episodic laryngospasm due to de novo SCN4A mutations: a new treatable disorder.

BACKGROUND: Myotonia is unusual in infants, and not well-known. METHODS: We describe neonatal life-threatening features of myotonia caused by de novo mutations in the muscle sodium channel gene SCN4A. RESULTS: Three male neonates initially displayed episodic laryngospasms, with face and limb myotonia appearing later. We found SCN4A de novo mutations in these neonates: p.Gly1306Glu in 2 unrelated cases and a novel mutation p.Ala799Ser in the third. Two patients survived their respiratory attacks and were efficiently treated by sodium channel blockers (mexiletine, carbamazepine) following diagnosis of myotonia. CONCLUSION: Severe neonatal episodic laryngospasm is a new phenotype caused by a sodium channelopathy, which can be alleviated by channel blockers.

[Usefulness of systematic brain magnetic resonance imaging in children with neurofibromatosis type 1]. / La réalisation systématique de l'imagerie par résonance magnétique cérébrale a-t-elle un intérêt chez l'enfant atteint de neurofibromatose de type 1?

BACKGROUND AND AIM: The aim of this study was to evaluate the usefulness of systematic screening of asymptomatic neurofibromatosis type 1 (NF1) children with magnetic resonance imaging (MRI). PATIENTS AND METHODS: We retrospectively reviewed the MRIs of children diagnosed with NF1 disease according to the National Institutes of Health criteria, who had been followed for at least 1 year by the department of pediatric neurology (Lyon, France). Brain MRI was systematically performed in asymptomatic patients under 6 years of age. RESULTS: One hundred patients with a median follow-up of 3.7 years (range, 1-8.6 years) were reviewed. Brain MRI was performed in a total of 94 children. Nine optic pathway gliomas were detected in symptomatic patients. Six children had symptoms caused by the tumor. Gliomas remained stable in 10 patients; 1 symptomatic glioma in an 8-year-old girl required treatment. Spontaneous regression was seen in 1 patient. CONCLUSION: Our results suggest that MRI screening of asymptomatic children to detect optic pathway gliomas does not improve the therapeutic decision and should not be performed systematically. We suggest further investigation in collaboration with the French NF Network.

[Acute hemiparesis revealing a neuroborreliosis in a child]. / Hémiparésie aiguë révélatrice d'une neuroborréliose chronique chez un enfant.

We report on a 11-year-old boy who had 2 acute hemiparesis episodes over a period of 1 month. He suffered from headache and fatigue since 1 year. He could not remember neither a tick bite nor a local erythematous skin lesion. The diagnosis of neuroborreliosis was based on intrathecal production of specifics antibodies. Furthermore, the CSF/blood glucose ratio was decreased (0.14), which was rarely described. Cranial MRI showed left capsulothalamic inflammation and a vasculitis. The patient was successfully treated by ceftriaxone. Neuroborreliosis should be considered in all children with stroke-like episode, even in the absence of a history of a tick bite.