RESUMO
INTRODUCTION: Transcobalamin (TC) transports cobalamin (vitamin B12) from plasma into cells. Its congenital deficiency is a rare autosomal recessive disorder due to mutations in the TCN2 gene. It causes intracellular cobalamin depletion with early onset in the first months of life, failure to thrive with pallor due to megaloblastic anemia. It can be associated with pancytopenia, gastrointestinal symptoms with vomiting, diarrhea, and neurological complications with myelopathy. Aggressive vitamin B12 parenteral therapy must be instituted early and continuously. Retinopathy and maculopathy are rarely associated with this condition. SUBJECT: We report the electrophysiological results of one TC-deficient patient diagnosed at the age of 4 months immediately and continuosly treated by hydroxocobalamin IM. Her visual function was followed by eight ophthalmological assessments, eight flash-ERG, six EOG, one mf-ERG, and seven P-ERG recordings over a 10-year period, between the age of 2y 9 m and 12y 6 m. RESULTS: Her ophthalmological assessment including visual acuity, fundi, optical coherent tomography (OCT), and retinal nerve fiber layer (RNFL) remained normal. From the age of 2y 9 m to 5y, dark-adapted and light-adapted flash-ERGs, EOGs and pattern-ERG were normal. From the age of 6y 4 m to 12y 6 m, dark-adapted flash-ERGs and EOGs remained normal. Cone a-wave amplitudes remained normal, whereas cone b-wave and flicker-response amplitudes were decreased. At the age of 12y 6 m, mf-ERG N1P1 amplitudes on the central 30° were decreased. From the age of 7y 4 m to 12y 6 m, P-ERG P50 amplitudes were decreased with no N95. COMMENTS: While clinical and anatomical assessments remained normal over a 10-year period, patient's electrophysiological results suggested the progressive onset of a subclinical retinopathy of inner-cone dystrophy type, and a subclinical maculopathy on the central 30° including the ganglion cell layer deficiency on the central 15°, despite continuous intramuscular treatment, RPE and scotopic system remaining normal. The origins of such subclinical retinopathy and maculopathy are unknown and independent of early disease identification and aggressive intramuscular hydroxocobalamin therapy.
Assuntos
Degeneração Macular , Doenças Retinianas , Criança , Pré-Escolar , Eletrorretinografia , Feminino , Seguimentos , Humanos , Hidroxocobalamina/uso terapêutico , Lactente , Doenças Retinianas/diagnóstico , Doenças Retinianas/tratamento farmacológico , Doenças Retinianas/etiologia , Transcobalaminas/genética , Vitamina B 12RESUMO
INTRODUCTION: Neuronal ceroid lipofuscinoses (CLN) are neurodegenerative disorders among the most frequent, inherited as an autosomal recessive trait. Affected patients can present with progressive decline in cognitive and motor functions, seizures, a shortened life span and visual deficiency. CLN2 is one of the rare CLN that benefits from treatment by cerliponase alpha an enzyme replacement therapy. Preliminary results on treated animal models have shown delayed neurological signs and prolonged life span. However, cerliponase alpha did not prevent vision loss or retinal degeneration in those animal models. Cerliponase alpha has currently been delivered to a few CLN2-affected patients. We report the case of one patient suffering from CLN2 treated with intracerebroventricular infusions of cerliponase alpha 300 mg every two weeks. Evolution of his retinal function was assessed by three successive flash-ERG and flash-VEP recordings throughout his treatment over a 4-year period. RESULTS: Before treatment at the age of 4 years 5 months, patient's retinas were normal (normal fundi and normal flash-ERG). After 29 infusions at the age of 6 years 10 months, a-wave combined response was absent, while cone and flicker responses were normal. After 80 infusions at the age of 8 years 9 months, a-wave cone response was absent with b-wave peak time increased, and no combined response. COMMENTS: Despite treatment, our patient's retinas showed a progressive abnormal and inhomogeneous function. Rods function was altered first, then the scotopic system and afterward, the cones. This result differs from those recorded in animal models. The relative preservation of cone functioning for a while could not be unequivocally attributed to enzyme replacement therapy as we lack comparison with the evolution of flash-ERGs recorded in untreated subjects.
Assuntos
Lipofuscinoses Ceroides Neuronais , Degeneração Retiniana , Animais , Criança , Pré-Escolar , Eletrorretinografia , Terapia de Reposição de Enzimas , Humanos , Lipofuscinoses Ceroides Neuronais/tratamento farmacológico , Retina/diagnóstico por imagem , Regulador Transcricional ERG , Tripeptidil-Peptidase 1RESUMO
BACKGROUND: LCHAD (long-chain 3-hydroxyacyl-CoA dehydrogenase) deficiency is a rare genetic disorder of mitochondrial long-chain fatty acid oxidation inherited as a recessive trait. Affected patients can present with hypoglycaemia, rhabdomyolysis and cardiomyopathy. About half of the patients may suffer from retinopathy. CASE REPORT: A 19-year-old girl was diagnosed as suffering from LCHAD deficiency with recurrent rhabdomyolysis episodes at the age of 7 months by an inaugural coma with hypoglycaemia and hepatomegaly. Appropriate dietary management with carnitine supplementation was initiated. Retinopathy was diagnosed at age two. Ophthalmological assessments including visual acuity, visual field, OCT, flash ERGs, P-ERG, flash VEPs and EOG recordings were conducted over a 17-year period. RESULTS: Visual acuity was decreased. Fundi showed a progressive retinopathy and chorioretinopathy. Photophobia was noticed 2 years before the decrease in photopic-ERG amplitude with normal scotopic-ERGs. Scotopic-ERG amplitude decreased 10 years after the decrease in photopic-ERG amplitude. No EOG light rise was observed. Flash VEPs remained normal. These results suggest that the cone system dysfunction occurs largely prior to the rod system dysfunction with a relative preservation of the macula function. COMMENTS: This dysfunction of cones prior to the dysfunction of rods was not reported previously. This could be related to mitochondrial energy failure in cones as cones are greater consumers of ATP than rods. This hypothesis needs to be further confirmed as other long-chain fatty oxidation defective patients (VLCAD and CPT2 deficiencies) do not exhibit retinopathy.