[Pontocerebellar hypoplasia type 1: a case report]. / Hipoplasia pontocerebelosa tipo 1: aportación de un caso.

INTRODUCTION: Pontocerebellar hypoplasias constitute a group of hereditary neurodegenerative disorders of uncertain aetiopathogenesis. They have been reported as being associated with deficiencies of complexes in the mitochondrial respiratory chain (MRC) and with congenital disorders of glycosylation. On the basis of clinical and neuropathological criteria, two phenotypes can be distinguished in this condition. Pontocerebellar hypoplasia type 1 is characterised by hypoplasia of the pons and the cerebellum associated with the degeneration of the motor neurons in the anterior horn of the spinal cord. CASE REPORT: A 4-year-old female with symptoms of severe psychomotor retardation associated with microcephaly, important generalised hypotonia, muscle hypotrophy, contractions in the four limbs, absence of stretch reflex and epilepsy with onset in the neonatal period. Magnetic resonance imaging of the brain revealed pontocerebellar hypoplasia. An electroneuromyography showed a trace that was compatible with axonal neuropathy and a biopsy of the deltoid muscle revealed the existence of neurogenic muscular atrophy. In the MRC study conducted in muscle homogenate and in skin fibroblasts, complex IV values were found to be at the lower limits of what could be considered to be normal levels. Results of the genetic study for spinal muscular atrophy were negative. CONCLUSIONS: The case reported here could be included as a case of pontocerebellar hypoplasia type 1. MRC studies can be of interest in cases of pontocerebellar hypoplasia in order to explain the role it plays in this disorder.

Congenital hydranencephalic-hydrocephalic syndrome associated with mitochondrial dysfunction.

We report the case of a 3-year-old girl, the only child of a nonconsanguineous couple without relevant antecedents, who was born with hydranencephalic-hydrocephalic syndrome diagnosed by ultrasonography at gestation week 28, and who was treated during the neonatal period by implantation of a ventriculoperitoneal shunt. She showed severe mental retardation, and died at age 4 years following an acute respiratory infection. Due to persistently high lactic acid levels in blood, muscle and skin biopsies were taken. Analysis of muscle biopsies revealed microscopic and ultrastructural alterations typical of mitochondrial disorders, and low levels of complexes III and IV of the mitochondrial respiratory chain. The enzymes of the pyruvate dehydrogenase complex showed normal activities in cultured skin fibroblasts. These findings raise the possibility that at least some cases of congenital hydranencephalic-hydrocephalic syndrome may be due to alterations in the mitochondrial respiratory chain.

Leber's congenital amaurosis associated with mitochondrial dysfunction.

We report the case histories of two 6-month-old girls, both with young, nonconsanguineous parents, referred to us for suspected blindness. In both cases, Leber's congenital amaurosis was diagnosed. Due to persistently high lactic acid levels in blood, muscle biopsies were taken. Analysis of biopsies revealed that both patients had low levels of complex IV of the mitochondrial respiratory chain; one patient additionally had low levels of complex III. Microscopic and ultrastructural alterations of muscle, typically observed in mitochondrial disorders, were observed only in the second patient. These observations raise the possibility that at least some cases of Leber's congenital amaurosis may be due to alterations in the mitochondrial respiratory chain.

Congenital hydranencephalic-hydrocephalic syndrome with proliferative vasculopathy: a possible relation with mitochondrial dysfunction.

We report the case of a fetus aborted at gestation week 20 because of hydranencephalic-hydrocephalic syndrome. The fetus was the third pregnancy of a nonconsanguineous couple whose first child exhibited congenital hydranencephalic-hydrocephalic syndrome associated with muscle histology findings consistent with mitochondrial cytopathy and deficiency of complexes III and IV of the respiratory chain and whose second pregnancy had terminated in an elective abortion on detection of progressive hydrocephalus at gestation week 19. The third pregnancy had a normal course according to obstetric and ultrasonography examinations performed at gestation weeks 5, 10, and 15, and negative results were obtained in standard serologic and polymerase chain reaction (PCR) tests for prenatal infections of the mother. However, the ultrasonography examination at gestation week 18 revealed hydrocephalus, in response to which the parents requested an abortion, which was performed at gestation week 20; the fetus was male and with no evident external malformations. Histopathologic studies of the brain and medulla oblongata revealed proliferative vasculopathy (glomeruloid vessels, intracytoplasmic inclusions, and microcalcifications) and intracytoplasmic inclusions in the voluntary muscle. Microbiologic and PCR tests of hepatic and spleen tissue were negative for prenatal infections. In view of the precedent of a sister with mitochondrial dysfunction, these findings raise the pos sibility that at least some cases of familial syndrome of congenital hydranencephalic-hydrocephalic syndrome with proliferative vasculopathy can be attributed to alterations in the mitochondrial respiratory chain.

Intradural cervical chordoma. Case report.

We describe a rare case of an intradural spinal chordoma. Only two cases have been previously reported and it is the second case diagnosed with MRI. A 65-year-old man presented with progressive disturbance of gait and weakness in the lower extremities. MRI revealed a intradural C6-C7 isointense mass, on T1- and T2-weighted images. The lesion enhanced after injection of gadolinium. The lesion was totally removed without difficulty by a C6-D1 laminectomy. Microscopic examination of the tumor revealed a chordoma. This is the third case in the literature of an intradural spinal chordoma. The appearance of this tumor with MRI may be similar to the chordomas of other locations.

[Epidermoid cyst: a rare cause of cystic liver disease]. / Quiste epidermoide: una causa infrecuente de patología quística hepática.

We present the case of a 42-year-old male patient with a large hepatic cyst, simulating a hydatid cyst. Subtotal cystectomy was performed. Thirteen months after this procedure the patient relapsed and a second laparotomy and total cystectomy were performed. A histopathological diagnosis of epidermoid cyst of the liver was made. The differential diagnosis of epidermoid cysts of the liver is broad and definitive diagnosis is usually only obtained after pathological examination of the surgical specimen. For this reason, and because of the potential for neoplasia, complete resection of the hepatic lesion should be attempted.

[Cemento-ossifying fibroma of the skull]. / Fibroma cemento osificante del cráneo.

Cemento-ossifying fibroma (cementoma) is benign fibro-osseous lesion of bone that generally is first seen during childhood or young adulthood as asymptomatic or painful intraosseous mass that commonly involved the maxilla. This paper describes the case of a young boy with a cemento-ossifying fibroma of the skull.

[Early onset adhalinopathy (LGMD2D) mimicking congenital muscular dystrophy]. / Adhalinopatía primaria (LGMD2D) de inicio en los primeros meses de la vida que simula una distrofia muscular congénita.

INTRODUCTION: The recent discovery of the dystrophin-associated complex of glycoproteins led to the delineation of sarcoglycanopathies, a phenotypically similar to dystrophinopathies group of clinically heterogeneous and progressive muscular dystrophies. The objective of this paper is to report the clinical, biochemical, histological, immunohistochemical and molecular genetics characteristics observed in a case of adhalinopathy (alpha-sarcoglycanopathy or LGMD2D) presenting in early months of life and resembling congenital muscular dystrophy. CLINICAL CASE: An 12-year old school boy, the third son of a healthy, young, non consanguineous couple, presented at birth with bilateral cleft lip, cleft palate and mild hypotonia. At age 6 months it was believed he suffered from a benign form of congenital muscular dystrophy on the basis of clinical, biochemical, electrophysiological and histological findings. From 5 years onwards he had frequent falls and climbing stairs had become increasingly difficult. Also, a positive Gowers 'sign, mild calf hypertrophy, high serum creatine-phosphokinase level and myopathic electromyographic features were present; otherwise, cardiological evaluation and intelligence were normal. A repeated muscular biopsy at 10 years showed dystrophic features as well as selective deficiency of adhalin on immunostaining. DNA analysis demonstrated the patient being homozygote for a R77C mutation. Actually, a marked lumbar lordosis and waddling gait, an impossibility of climbing stairs and arising from the floor in addition to absent rotulian reflexes and mild Achilles retraction are present. CONCLUSIONS: LGMD2D may present in the first months of life mimicking congenital muscular dystrophy. It seems reasonable that biopsies of all new cases of muscular dystrophies be selectively immohistochemical analyzed, and when it is possible the diagnosis should be confirmed by DNA analysis.

[Muscular dystrophy due to a deficit of gamma-sarcoglycan. A report of three patients with the Delta-521t mutation]. / Distrofia muscular por déficit de gamma-sarcoglicano. Aportación de tres pacientes con la mutación Delta-521T.

INTRODUCTION: gamma-sarcoglicanopathies, also classified as limb girdle muscular dystrophy type 2C (LGMD2C) are a group of autosomal recessive muscular dystrophies due to mutations in 13q12 and subsequent g sarcoglican deficiency. The protein is one of the components of the dystrophin associated glycoprotein complex and is thought to impart structural integrity to the myofibre. The clinical course of the disease may be heterogeneous, ranging from severe forms with onset in the first decade and rapid progression resembling Progressive Duchenne muscular dystrophy (DMD) to milder forms with later onset and slower course. Cases hitherto reported in Spain corresponds to gypsie patients, homozygous for C283Y missense mutation. CASE REPORTS: Here, we report three new galician (Northwest Spain) patients (one male and one female sibling cases) with a severe DMD like muscular dystrophy homozygous for D 521T. In the first male familial case, initial diagnosis of DMD was made. On reevaluation fourteen years later, inmunohistochemical and molecular studies allowed for a definitive g sarcoglicanopathy diagnosis. CONCLUSIONS: Patients with a primary sarcoglycanopathy may be clinically indistinguishable from those with the primary dystrophinopathies. Probably, the diagnosis of LGMD are underestimated and a number of male patients diagnosed as DMD really corresponds to a recessive form o muscular dystrophy. Consequently, a definitive diagnosis rests on appropriate inmunohistochemical and molecular analysis, specially in those patients showing a normal pattern of dystrophin and/or suggestive for an autosomal recessive mode of inheritance.

[Mixed hypotonia, neurological regression and atrophy of the cerebellum: manifestations that suggest infantile neuroaxonal dystrophy]. / Hipotonía mixta, regresión neurológica y atrofia cerebelosa: manifestaciones sugestivas de distrofia neuroaxonal infantil.

INTRODUCTION: Infantile neuroaxonal dystrophy (INAD), or Seitelberger disease, is a neurodegenerative disease of unknown origin which is transmitted by autosomal recessive inheritance. Clinically, it courses with psychomotor stagnation and regression that begins at the age of one or two years, associated to hypotonia with mixed clinical features (segmentary and suprasegmentary) that progresses towards spastic tetraplegia and progressive optic atrophy and dementia; this leads to death before the age of ten years. AIMS. To present the case of a 30 month old child with INAD, in whom a N acetylgalactosaminidase deficiency and mitochondrial cytopathy were ruled out. CASE REPORT: Male aged 30 months with an initial overall retardation, and later regression, of psychomotor acquisitions. In the physical exploration the patient displayed serious neurological involvement with mixed hypotonia, muscular hypotrophy with generalised weakness and mild bilateral horizontal nystagmus. Complementary explorations with neuroimaging revealed a slight increase in the subarachnoid space, with atrophy of the vermis and cerebellar hemispheres. Neurophysiological tests (EMG and ENG), which were initially normal, later showed signs of denervation in the EMG, and the ENG revealed a decreased amplitude of motor responses, with preservation of conduction speed. Histological tests showed the presence of axons with axoplasm expanded by the inclusion of typical tubulovascular structures. CONCLUSION: The clinical features of our patient met all the criteria to satisfy a diagnosis of INAD, and he displayed a classic form of the disease. INAD must be considered when the clinician is faced with: 1. A clinical picture of stagnation and later regression of psychomotor development before the age of two years; 2. Hypotonia, muscular atrophy and initial overall areflexia, with later progression towards pyramidalism; 3. Initially normal EMG findings, with later signs of denervation; 4. Cerebellar atrophy (hemispheres and vermis); 5. Visual deficit, and 6. Histopathological proof of characteristic findings.

[Mitochondrial encephalomyopathies and West's syndrome: a frequently underdiagnosed association]. / Encefalomiopatías mitocondriales y síndrome de West: una asociación frecuentemente infradiagnosticada.

INTRODUCTION: West's syndrome is known to have symptomatic, cryptogenetic and idiopathic forms. Greater knowledge of the different pathologies and the development of new diagnostic techniques have allowed the list of symptomatic forms to be extended and congenital disorders of the metabolism account for a significant percentage as an aetiopathogenic factor. Yet, although it is known that mitochondrial cytopathies can trigger the development of West's syndrome, few reports exist concerning their association. AIMS: Our aim in this paper is to report on four cases of West's syndrome in which a mitochondrial cytopathy was shown to be an aetiopathogenic factor. CASE REPORTS: Two females and two males aged between 2 and 10 months, who were suffering from West's syndrome. Biochemical and neuroimaging findings suggested a possible mitochondrial cytopathy, which was later confirmed in the four cases on observing a partial deficiency of some of the complexes of the mitochondrial respiratory chain in muscles; this was found to be simple in the first three (complexes III, I and IV, respectively) and combined in the fourth (complexes I and IV). CONCLUSIONS: Infantile spasms should be considered as one of the ways mitochondrial encephalomyopathies manifest themselves. As part of the process of diagnosing West's syndrome, we recommend tests be carried out to determine the levels of lactic and pyruvic acid, carnitine and amino acids in plasma, and possibly in the cerebrospinal fluid, as well as those of amino acids and organic acids in urine. A muscular biopsy must also be carried out in patients who are strongly suspected of having a mitochondrial cytopathy, as well as the corresponding molecular genetic study.

[Multiple symmetric lipomatosis associated to polyneuropathology, atrophy of the cerebellum and mitochondrial cytopathy]. / Lipomatosis simétrica múltiple asociada a polineuropatía, atrofia de cerebelo y citopatía mitocondrial.

INTRODUCTION: Multiple symmetric lipomatosis (MSL), which is predominantly found in middle aged males, is characterised by accumulations of fat in the neck, shoulders and other parts of the trunk, and sometimes associated with different neurological manifestations, both central and peripheral. Although its aetiology is unknown, it has been described as associated with mitochondrial cytopathies. AIMS. To describe the case of a young female with MSL associated with mitochondrial encephalomyopathy. CASE REPORT: Girl aged 14 with MSL, ataxia, patellar hyperreflexia, bilateral Babinski sign, pes cavus, axonal peripheral neuropathy, involvement of the optic pathway, atrophy of the cerebellum, subsarcolemmal mitochondrial accumulations in the untrastructural examination of the vastus lateralis muscle and partial deficit of complex I in the mitochondrial respiratory chain. As regards molecular genetic aspects, the most frequent mutations of the ATPase 6 gene in lymphocytes, and mtDNA deletions and tRNALys and tRNALeu(UUR) mutations in muscles were excluded. CONCLUSIONS: Despite the fact that MSL is an entity normally found in adults, the possibility of its being diagnosed in the paediatric age must be taken into account. This case is probably the second time MSL has been observed associated with mitochondrial cytopathy in this age bracket.

[Severe form of juvenile type II glycogenosis in a compound-heterozygous boy (Tyr-292--> Cys/Arg-854-->Stop)]. / Forma grave de glucogenosis tipo II juvenil en un niño heterocigoto compuesto (Tyr-292-->Cys/Arg-854-->Stop).

INTRODUCTION: Type II glycogenosis is a glycogen storage disease inherited as an autosomal recessive trait. This molecular and clinically heterogeneous condition is due to a deficiency in a lysosomal acid 1,4-alpha-glucosidase. OBJECTIVE: To report the clinical, enzymatic and molecular characterization of a mulatto child, born to healthy Dominican mother and Caucasian father, affected by the juvenile phenotype form of type II glycogenosis. CLINICAL CASE: This 16-month-old male presented from 10 months with motor delay, limb-girdle hypotonia, prominence of calves, increased CPK value, mixed myotonic/myopathic pattern on EMG, intense glycogen muscle storage (775 micrograms/mg of protein) and severe deficiency of 1,4-alpha-glucosidase activity (< 0.03 mU/mg of protein). At 24 months he developed a rapidly progressive hypotonia and respiratory failure. The patient was found to be compound heretozygote for the novel mutation Tyr-292-->Cys, coming from the father, and Arg-854-->Stop, coming from the mother and previously reported in two Afroamerican patients, one with the adult phenotype and the other with the juvenile one. CONCLUSIONS: The present case corresponds to a severe form of type II juvenile glycogenosis. The severity of this condition may be related to the observed mutations and the associated extremely low muscle enzymatic activity.

[Western type cerebro-muscular dystrophy and congenital merosin deficiency muscular dystrophy: two terms for the same disorder]. / Distrofia cerebromuscular tipo occidental y distrofia muscular congénita deficiente en merosina: dos denominaciones para una misma entidad.

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.

[Mitochondrial encephalopathies]. / Encefalomiopatías mitocondriales.

OBJECTIVE: We carry out a review of the current basic genetic, biochemical, clinical, diagnostic and therapeutic aspects of mitochondrial cytopathies due to deficiencies in the mitochondrial respiratory chain complexes, which appear clinically during childhood and/or adolescence. DEVELOPMENT: The clinical description has been divided into two groups: mitochondrial cytopathies secondary to alterations of mitochondrial DNA (mtDNA) and mitochondrial cytopathies secondary to alterations of the nuclear DNA (nDNA); we also consider about the importance of such conditions at this age.

[Hereditary neuropathy with liability to pressure palsies (tomaculous neuropathy). Clinical, electrophysical and molecular study of two affected families]. / Neuropatía hereditaria con paralisis sensible a la presión (neuropatía tomacular). Estudio clínico, electrofisiológico y molecular de dos familias afectadas.

INTRODUCTION: Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant disorder of peripheral myelin characterized by episodes of recurrent mononeuropathies usually involving nerves at common sites of entrapment and compression. Additional features include evidence of a diffuse demyelinating sensorimotor polyneuropathy on nerve conduction studies, focal myelin thickening (tomacula) on sural nerve biopsy, and a 1.5 Mb deletion on 17p11.2 encompassing the peripheral myelin protein 22 (PMP22) gene in most families. PATIENTS AND METHODS: Two girls, aged 10 and 12 years, presented with peroneal nerve palsy and peroneal nerve palsy plus tibial nerve palsy, respectively. In none case, a clear causal factor was recognizable. Neurophysiological studies: both cases showed diffuse sensory and motor nerve conduction velocity slowing and prolongation of distal motor latencies. In addition, features of focal entrapment neuropathy were obtained at proximal peroneal nerve level. Sural nerve biopsy: large axons demyelination, redundant myelin and intraaxonal looping (case 1) and tomaculas (case 2). Molecular genetics: 17p12-p11 deletion was demonstrated in both affected girls, the mother and two maternal uncles of case 1 and in the father, paternal grandfather and two paternal uncles of case 2. CONCLUSIONS: NHPP should be suspected in cases of peripheral neuropathy without clearly recognizable cause. Electrophysiological and molecular studies permit both delineation of the condition and identification of otherwise clinically normal family members.