Inherited metabolic disorders involving the eye: a clinico-biochemical perspective

Abstract

The diagnosis of inborn errors of metabolism is challenging for most physicians. Improvements in medical technology and greater knowledge of the human genome are resulting in significant changes in the diagnosis, classification, and treatment of inherited metabolic disorders (IMDs). Many known inborn errors of metabolism will be recognised earlier or treated differently because of these changes. It is important that physicians recognise the clinical signs of IMDs and know when to propose advanced laboratory testing or referral to a higher centre for better patient management. Ocular manifestations occur in various metabolic disorders. Although there is an extensive understanding of many inborn errors of metabolism at the biochemical, molecular, and metabolic levels, little is known about their pathogenesis. In particular, how systemic metabolic disease contributes to ocular defects remains to be elucidated in IMDs. The occurrence of eye abnormalities could be due to direct toxic mechanisms of abnormal metabolic products or accumulation of normal metabolites by errors of synthetic pathways or by deficient energy metabolism. A detailed ophthalmological assessment is essential. Definitive diagnosis and management of patients with IMDs is ideally carried out by a combination of specialists, including an ophthalmologist, paediatrician, biochemist, and medical geneticist. Recent advances in the diagnosis and treatment of IMDs have substantially improved the prognosis for many of these conditions.

Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss

“…Inborn errors of metabolism constitute a heterogeneous group of disorders that affect metabolic pathways due to underlying genetic defects [201] and result in abnormalities in the synthesis or catabolism of biomolecules [201,202]. Many such inborn errors of metabolism are known to be associated with PR cell loss, manifested either as a primary ocular defect or as part of a systemic disease [201]. PR cells, with their high metabolic activity, are particularly vulnerable to defects in metabolism of biomolecules such as lipids, carbohydrates, nucleotides, and proteins, which provide energy and serve many other functions described below.…”

An Ophthalmological Study of Ectopia Lentis, With Multifarious Aetiopathogenesis, Diverse Clinical Presentations and Varied Prognoses

“…Along with the corrective refractive surgeries, homocystinuria often responds to a low methionine diet and and adding cysteine, along with high doses of pyridoxine (Vitamin B6) and folic acid. 17,18,19 For recognition, diagnosis and management of homocystinuria due to cystathionine ßsynthase deficiency, a guideline was developed as a part of the European network and registry for homocystinuria and methylation defects (E-HOD), which was further revised, and systematic literature review and evidence grading was done using the Scottish Intercollegiate Guideline Network (SIGN) methodology, resembling the characterisation of Marfan's syndrome by the revised Ghent nosology. 20,21 Systemic manifestations include mental retardation, hypopigmentation of skin and hair, thromboembolic events and marfanoid habitus.…”

Remembering MUDPILES: A Case of Unexplained Metabolic Acidosis

“…Ophthalmologic examination is also helpful because ocular manifestations occur in various metabolic disorders and can involve the cornea, lens, retina, or optic nerve. 6 The lactate-to-pyruvate ratio is useful to distinguish possible inborn errors of metabolism. A high lactate-to-pyruvate ratio (.30) has a differential diagnosis of pyruvate carboxylase deficiency, a-ketoglutarate dehydrogenase deficiency, and mitochondrial defect of oxidative phosphorylation.…”