Congenital ocular motor apraxia (COMA), first described by Cogan [Trans Am Acad Ophthalmol Otolaryngol 1952;56:853-862], is a rare disorder characterized by impairment of voluntary and optically induced horizontal eye movements and compensatory head thrust. The causes and pathogenesis of COMA are poorly understood. It frequently occurs in association with other neurologic abnormalities including non-progressive congenital disorders of the central nervous system (CNS), various systemic diseases and chromosomal alterations. Here, we report the case of a 6-month-old girl with psychomotor retardation, myopathy and clinical features of COMA, associated with external hydrocephalus and mitochondrial dysfunction (partial deficiency of the respiratory-chain enzyme NADH dehydrogenase). In view of this finding, we recommend that tests to characterize patients with COMA should include determination of blood levels of lactic and pyruvic acid.

Apraxias↗

PubMed1998

Clinical heterogeneity associated with mitochondrial DNA depletion in muscle.

We studied 10 patients with a variable degree of mtDNA depletion in muscle. Seven patients showed a clear-cut myopathic pattern, while the three remaining had brain involvement. There was no relationship between age at onset and relative mtDNA copy number in muscle, but we found an apparent correlation between clinical severity and degree of muscle mtDNA depletion. Muscle morphology showed that mtDNA depletion was associated with mitochondrial proliferation and cytochrome c oxidase negative fibers. Biochemical studies revealed single or combined defects of mtDNA-dependent respiratory chain complexes. Our data indicate that patients with mtDNA depletion may have a more variable age at onset and clinical evolution and wider phenotype than previously thought. The diagnosis of this condition, so far regarded as rare, may have been overlooked to some extent.

Age Factors↗

PubMed1998

Serum carnitine levels in epileptic children before and during treatment with valproic acid, carbamazepine, and phenobarbital.

Serum levels of free, acyl, and total carnitine were determined in 32 patients with seizures, before and after 3, 6, and 12 months of treatment with valproic acid (17 patients), carbamazepine (10 patients), or phenobarbital (5 patients). In all three treated groups, both free and total carnitine levels showed a significant decline with respect to pretreatment levels. This decline was most marked and most consistent in patients treated with valproic acid. In 35% of the patients in this group, carnitine deficiency (ie, total carnitine < 30 micromol/L) was observed by month 12. In none of the three groups were serum carnitine levels significantly correlated with the serum concentration of the drug. These findings suggest a need to monitor serum carnitine levels in children treated with any of these drugs.

Adolescent↗

PubMed1998

[Protocols and basic clinical norms to follow in order to obtain the certificate of eradication of poliomyelitis in Spanish territory].

Explore the source record for details and available documents.

Adolescent↗

PubMed1998

[3-hydroxy-3-methylglutaric aciduria and recurrent Reye-like syndrome].

INTRODUCTION: 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA lyase) is an inborn error of ketogenesis and Leucine catabolism. HMG-CoA lyase catalyses the final step in leucine degradation, converting HMG-CoA to acetyl-CoA and acetoacetic acid. Clinical manifestations include hepatomegaly, lethargy or coma and apnoea. Biochemically there is a characteristic absence of ketosis with hypoglycemia, acidosis, hipertransaminasemia and variable hyperammoniemia. The urinary organic acid profile includes elevated concentrations of 3-hydroxy-3-isovaleric, 3-hydroxy-3-methylglutaric, 3-methylglutaconic and 3-methylglutaric acids. CLINICAL CASE: Here, we report the case of a 17-year-old girl who presented in both ten months and five years of age a clinical picture characterized by lethargy leading to apnea and coma, hepatomegaly, hypoglycemia, metabolic acidosis, hyperammoniemia, elevated serum transaminases and absence of ketonuria. Diagnostic of Reye syndrome was suggested by hystopathologic finding of hepatic steatosis and clinical and biochemical data. As of 11 years old, laboratory investigations revealed carnitine deficiency and characteristic aciduria. Confirmatory enzyme diagnosis revealing deficiency of HMG-CoA lyase was made in cultured fibroblasts. CONCLUSION: Our report constitutes an example of the presentation of HMG-CoA lyase deficiency as recurrent Reye-like syndrome.

Acidosis↗

PubMed1998

[Western type cerebro-muscular dystrophy and congenital merosin deficiency muscular dystrophy: two terms for the same disorder].

INTRODUCTION: Congenital muscular dystrophies (CMD) are a clinically heterogeneous group of muscular disorders characterized by hypotonia, muscle weakness and early or congenital joint contractures. Electromyography reveals a myopathic pattern, creatine-kinase (CK) may be moderately elevated and muscle biopsy shows pathological changes consistent with a dystrophic process. OBJECTIVE: Report the cases of two brothers with 'Occidental type cerebro-muscular dystrophy' versus 'merosin-deficient CMD'. PATIENTS AND METHODS: Two children, a boy and a girl, of a first consanguineous parents. In the first case, the diagnosis of Occidental type cerebro-muscular dystrophy was made in 1983, at the age of 4 years, according to clinical, biochemical, electromyographic, pathological and neuroradiological data. In the second case, the diagnosis of merosindeficient form of CMD was made with the same criteria and with immunohistochemistry and Western blot techniques in 1997, when she was 6 months old. CONCLUSION: Occidental type cerebro-muscular dystrophy, described 13 years ago by one member of our group, corresponds with merosin-deficient form of CMD.

Brain↗

PubMed1998

[Mitochondrial encephalomyopathies starting in childhood and adolescence].

INTRODUCTION: In this chapter we carry out a review of the current basic clinical and diagnostic aspects of mitochondrial cytopathies due to deficiencies in the mitochondrial respiratory chain complexes, which appear clinically during childhood and/or adolescence. DEVELOPMENT: The description has been divided into two groups: mitochondrial cytopathies secondary to alterations of the mitochondrial DNA (mtDNA) and mitochondrial cytopathies secondary to alterations of the nuclear DNA (nDNA). CONCLUSIONS: We conclude by considering the importance of such conditions at this age.

Adolescent↗

PubMed1998

[Treatment of mitochondrial diseases in childhood and adolescence].

The advances made in recent years in understanding this large group of disorders has led to the development of ways of approaching their treatment, although in most cases it is neither definitive nor curative. In this article we review current aspects of the treatment of defects: of substrate transport, substrate use, the Krebs cycle, the mitochondrial respiratory chain and oxidation-phosphorylation coupling. We conclude with comments on possible future treatment.

Adolescent↗

PubMed1997

[Hypomelanosis of Ito: autism, segmental dilatation of colon and unusual neuroimaging findings].

INTRODUCTION: Hipomelanosis of Ito (HI) also called Incontinentia pigmenti achromians, is the third most frequent neurocutaneous disorder. The abnormal skin lesions are more evident under Wood's lamp and consist of hypopigmented areas with irregular borders, streaks, whorls or patches which are usually distributed on the trunk or on the limbs. Non-cutaneous abnormalities, particularly of the central nervous system, eye, teeth and skeleton, have been reported in 76-94% of patients. CLINICAL CASES AND CONCLUSIONS: In the present paper, we report two cases of Hipomelanosis of Ito in two female girls with facial coarse features. In the first case the psychomotor development was normal. Segmental dilatation of the colon, precocious pubarchy, abnormal periventricular white matter hipersignal on MRI and nodular mass on left caudate nuclei were also present. In the second case a severe developmental delay and autistic behaviour were the prominent features. To our knowledge, findings described in case 1 were not previously reported in association with HI.

Autistic Disorder↗

PubMed1997

A two-base deletion in exon 6 of the 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL) gene producing the skipping of exons 5 and 6 determines 3-hydroxy-3-methylglutaric aciduria.

A novel two-base deletion in the 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL) gene was found in a Spanish patient with homozygous 3-hydroxy-3-methylglutaric aciduria. Amplification by RT-PCR of the mRNAs showed that the gene was transcribed into three different mRNAs. One showed the complete deletion of exons 5 and 6 located between nucleotides 348 and 561 of the HL cDNA. The second transcript showed deletion of exon 6 only, and the third contained a two-base deletion CT in exon 6, corresponding to nucleotides 504 and 505 of the HL cDNA. These aberrant mRNAs are predicted to encode three abnormal HMG-CoA lyase proteins; the first (from skipped exons 5 and 6) lacks 71 amino acids, which represents 24% of the mature protein; the second, (from the skipping of exon 6, producing a frameshift) contains only 192 amino acids, the last 26 of which are missense amino acids preceding a stop codon; the third contains only 175 amino acids, the last 7 of which are missense. Northern blot analysis showed that the HL mRNA levels of the patient were 4% of the control. PCR quantitative analysis indicated that the mRNA lacking exons 5 and 6 was the most abundant, representing 88% of the total. The other two mRNAs represented 8% and 4%, respectively. In the genomic DNA only one CT deletion was found at positions +7 and +8 at beginning of exon 6. No mutations were observed in the splice donor, splice acceptor, or pyrimidine-rich sequences of the intronic regions flanking exons 5 and 6. All three aberrant mRNAs resulted only from the deletion of nucleotides CT. We suggest that this deletion may affect the interaction between the small nuclear ribonucleoproteins (snRNPs) and exon 6, and that, as a result, the abnormal splicing of the pre-mRNA produces two different aberrant transcripts.

Adolescent↗

PubMed1997

[Striated osteopathy with cranial sclerosis and macrocephaly in childhood. Report of 2 cases].

INTRODUCTION: Osteopathia striata with cranial sclerosis (OS-CS) is a specific and rare bone dysplasia, with autosomal dominant inheritance. Radiographic features are typical: linear striations, particularly of long bones, and increased density mostly of the cranial basis. Facial impression is also typical, with frontal bossing, hypertelorism, epicanthic folds and both broad and depressed nasal bridge. Macrocephaly, usually present at birth, is likely to be the initial manifestation and has an uneventful course. CLINICAL CASES: Two girls, aged 3 years-5 months and 5 years-4 months with OS-CS and macrocephaly are reported here. They were evaluated from neonatal period for macrocephaly not complicated associated with peculiar facial appearance. At age of 3 years, radiologic examination showed linear striations of the long bones and sclerosis of the skull base. Their development were normal and no related deficiency was detected. Parents roentgenographs were normal. CONCLUSION: We conclude that OS-CS should be considered in the differential diagnosis in infants with macrocephaly without complications, specially if the facial appearance is striking.

Bone Diseases↗

PubMed1996

Congenital myopathy with type II muscle fiber hypoplasia.

An unusual congenital neuromuscular disease characterized by atypically small type II muscle fibers is reported. The patients were a 9-year-old boy and a 3-year-old boy, both of whom showed motor retardation with proximal muscle wasting and hypotonia. Muscle biopsy revealed hypoplastic type II fibers and normal type I fibers. The observed hypoplasia seems to be a primary alteration.

Biopsy↗

PubMed1996

Cerebrospinal fluid purine metabolites after complex febrile convulsions.

Adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine and uric acid were determined in cerebrospinal fluid (CSF) of 15 children after complex febrile seizures (CFS) and in 27 after simple febrile seizures (SFS), and compared with those in a control group of 63 children. There was no statistically significant difference between the groups for any of these metabolites, suggesting that CFS and SFS neither significantly disturb the metabolism of nucleotides, nucleosides or bases nor significantly deplete neuron adenosine triphosphate levels.

Child, Preschool↗

PubMed1996

Autosomal recessive hydrocephalus with aqueductal stenosis.

We report the case histories of three sisters with congenital hydrocephalus associated with stenosis of the cerebral aqueduct. The parents were a young consanguineous couple. In two cases hydrocephalus was detected before birth by ultrasonography. We consider these three cases to be of the rare autosomal form of hereditary hydrocephalus.

Cerebral Aqueduct↗