Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Bhanu K Bhakhri

"The Journal of Clinical and Diagnostic Research (JCDR) has been in operation since almost a decade. It has contributed a huge number of peer reviewed articles, across a spectrum of medical disciplines, to the medical literature.
Its wide based indexing and open access publications attracts many authors as well as readers
For authors, the manuscripts can be uploaded online through an easily navigable portal, on other hand, reviewers appreciate the systematic handling of all manuscripts. The way JCDR has emerged as an effective medium for publishing wide array of observations in Indian context, I wish the editorial team success in their endeavour"



Dr Bhanu K Bhakhri
Faculty, Pediatric Medicine
Super Speciality Paediatric Hospital and Post Graduate Teaching Institute, Noida
On Sep 2018




Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dematolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011

Important Notice

Reviews
Year : 2011 | Month : November | Volume : 5 | Issue : 7 | Page : 1467 - 1472

The Role of Radio-diagnosis in Inborn Errors of Metabolism

Sushil G. Kachewar, Smita B. Sankaye, Devidas S. Kulkarni

1. MD, DNB (Radio-diagnosis), Associate Professor, Rural Medical College (RMC), PIMS, Loni, India. 2. MD Pathology Registrar, Rural Medical College, PIMS, Loni, India. 3. MD Radio-diagnosis, Rural Medical College, PIMS, Loni , India.

Correspondence Address :
Sushil Kachewar, MD, DNB (Radio-diagnosis)
Associate Professor, Rural Medical College,
PIMS, Loni, India.
Phone: 9921160357
E-mail: sushilkachewar@hotmail.com

Abstract

Inborn Errors of Metabolism take a heavy toll of the patient as well as their relatives due to delayed diagnosis. These occur due to defective genes leading to various metabolic abnormalities. As genetic problems are countless, so are their manifestations. Timely identification of the disease entity is the key at least to a satisfactory, if not a complete successful management in many instances. Modes of presentation and clinical features are not always characteristic and have resemblance to routine day to day illnesses.

In this chaos, an appropriate use of modern strides in Imaging Sciences often enable to raise a strong suspicion in majority of the cases and even to confirm the clinical suspicion in some cases of inborn errors of metabolism. Not all of the medical fraternity is aware of this important role that radio-imaging can play. Hence a timely review of the Role of Radio-diagnosis in Inborn Errors of Metabolism is a must and is therefore attempted in this article. The author attempts to solve this diagnostic dilemma by discussing the role that each imaging modality can play to arrive at a final diagnosis. Multiple examples and images have been used generously to emphasize this point.

Keywords

Inborn errors of metabolism, Radiograph, Ultrasound, CT scan, MRI, MR Spectroscopy

Introduction
The term – ‘Inborn Errors of Metabolism (IEM)’, encompasses a plethora of metabolic abnormalities which result from gene related problems. A defective gene causes reduced or almost no formation of enzymes that are necessary for the normal functioning of various metabolic pathways, in such a way that the toxic substance starts accumulating in an abnormal amount to cause damage to various systems in the body in one form or the other.

Literat ure Review
Archibald Garrod originally put forth the hypothesis of one geneone enzyme and first used the term ‘Inborn Error of Metabolism’ for these inherited genetic, congenital disorders (1).

These disorders are broadly classified (1), depending upon the metabolic pathways which they affect the most. e.g. disorders of carbohydrate metabolism (e.g., glycogen storage disease), disorders of amino acid metabolism (e.g. phenylketonuria), disorders of organic acid metabolism (e.g. alkaptonuria) etc.

More than 500 types of these disorders have now been known to occur in humans (2). Although the isolated cases are rare, thecombined data is staggering in terms of their effect on the childhood health statistics. Hence, an early diagnosis is the need of hour, to ensure a better quality of life.

In British Columbia (1), the overall incidence was estimated to be 70 per 100,000 live births. In India, the exact burden of these metabolic abnormalities is still unknown, as there are no surveys which have targetted this specific question. However, the data (3),(4) suggest that out of the 25 million annual births in India; 8 lakhs suffer from congenital malformation; 3.5 lakhs from glucose 6 phosphate deficiency (G6PD); 25,000 from metabolic disorders; 20,000 from Down`s Syndrome, 15,000 from congenital hypothyroidism, 14,000 from thalassaaemias and 5,000 from sickle cell anaemias. When 4400 patients who were suffering from mental retardation were biochemically screened, it was found that 256 cases (5.75%) were caused by various inherited metabolic disorders.

Due to the myriad forms of these diseases, the patients present to the clinics with countless types of manifestations (5). The signs and symptoms are usually very non specific, like nausea, vomiting, failure to thrive and so on. Sometimes seizures and abnormal movements may also be seen.

H(2e)nce many times, when unsusp(e3c) ted patients are referred for various radiological examinations, certain characteristic radiological findings may be the first to raise a strong suspicion of the metabolic abnormalities and at times, may even be conclusive.

Role of Radio-diagnosis
1. Plain Radiographs: They are ordered as a routine workup for evaluating a sick child. Specific radiographs of certain body parts may be asked for, when such parts are affected and the results may even change the overall diagnosis. Here are a few examples (Table/Fig 4).

a. A plain radiograph of the knees, when it was asked for in a sick child with knee swelling (Table/Fig 1), showed features which were typical of rickets and indicated an improper vitamin D metabolism. It thereby aided in diagnosing an inborn error of metabolism in this unsuspected patient.

Nephrocalcinosis can also be demonstrated on a plain radiograph of the abdomen in patients in whom the end stage is reached in the form of renal osteodystrophy. b. Similarly, patients of Lipoid Proteinosis exhibit characteristic intracranial calcifications on the plain radiographs. c. Mucopolysacchridoses (Table/Fig 2) exhibit a proximal tapering of metacarpals, the deformed ends of the distal radius and the ulna, and the notching of vertebrae, that can be seen on plain radiographs as well. d. Inborn errors of metabolism which resulted from adrenal hyperplasia showed an advanced bone age of around 9-11 years in a child who actually was 2 years of age. e. Plain radiographs of the skull (Table/Fig 3) in a patient with Crouzon’s syndrome showed the premature closure of the calvarial and the cranial base sutures, as well as those of the orbit and the maxillary complex (craniosynostosis). There was complete penetrance and a variable expressivity in this autosomal dominant disorder (6). A mutation in the fibroblast growth factor receptor-2 (FGFR2) gene was the underlying cause, as the locus heterogeneity with causal mutations in FGFR2 caused Crouzon’s syndrome and that in FGFR3 caused Crouzon`s syndrome with acanthosis nigricans (7). f. Plain radiographs demonstrated the characteristic shortening of the first toe of both feet and abnormal soft tissue ossification in a case of Muchmeyer`s disease. It is an extremely rare, disabling disorder which causes the gradual ossification of the striated muscles, tendons, ligaments, fascia and aponeurosis (8). Although it is usuallysporadic, it may be inherited as an autosomal dominant disorder that has a wide range of expressions (9).

2. Ultrasound non invasively demonstrates the details of the internal organs and the soft tissue structures without any exposure to the ionizing radiations as in the plain radiographs or Computed Tomography (CT). a. Nephrocalcinosis (Table/Fig 5) in Renal Tubular Acidosis and renal osteodystrophy which was secondary to the malfunctioning of the Vitamin D metabolism could be demonstrated on the sonography of the kidneys which was carried out in a sick child who was made to undergo abdominal ultrasound as a routine procedure for nonspecific pain. b. Similarly, ocular ultrasound can demonstrate ectopia lentis (the outward and upward subluxation/dislocation of the lens) in a patient of Marfans Syndrome. c. Hereditary tyrosinaemia is an autosomal recessive, enzymatic disorder that manifests as micro- and macro nodular cirrhosis in early childhood. Hepatocellular carcinoma occurs in approximately one-third of the affected children (10), (11). d. Unexplained male hydrops (Table/Fig 7) can be seen in Barth’s Syndrome which is an X-linked multisystem disorder which is usually diagnosed in infancy and is characterized by cardiac problems like dilated cardiomyopathy, endocardial fibroelastosis, proximalmyopathy, feeding problems, growth retardation, neutropaenia, organic aciduria and variable respiratory chain abnormalities (12). e. On ultrasound, retinoblastoma can be seen as a mass lesion which arises from the retina (Table/Fig 8). A mutation in the long arm of chromosome 13 prevents the normal suppression of the development of retinoblastoma, resulting in retinoblastoma. MDM2 has been identified as the first modifier gene for retinoblastoma (13).

3. CTscan shows exquisite cross sectional details of the body structures. Although there is a risk of radiation exposure, the investigation is carried out only when the benefit outweighs the risks.

a. Lipoid Proteinosis (Table/Fig 9) demonstrates bilateral symmetric comma shaped intracranial calcifications. b. Alexander’s Disease shows bilateral frontal atrophy and symmetric hypo densities. c. Many IEMs have microcephaly. However, the clinical examination alone is insufficient in confirming whether it is pure microcephaly or it is just due to sutural fusion / craniostenoses. CT scan of the brain solves this dilemma by demonstrating unfused sutures in a patient who has a small appearing head size. d. Fibrous dysplasia (FD) is a congenital, non inheritable, genetic disorder in which the medullary bone is slowly replaced by fibro-osseous tissues, leading to the distortion and overgrowth of the affected bone, giving a characteristic ground glass appearance to the affected bone (Table/Fig 10). It results from the mutation of genewhich encodes for the alpha sub-unit of the stimulatory G protein in the bone marrow cells, leading to a locally increased stimulatory activity of adenyl cyclase and cAMP. This mutation causes an increased production of the C- fos protein and interleuekin-6, that results in a classic, dysplatic bone in FD (14).

4. MRI – shows the details of all the orthogonal planes without any risk of radiation exposure. It has the ability to strongly point towards an IEM as the cause of the patient’s suffering, especially so, when other special biochemical investigations are not available / feasible / results are pending. Neuroimaging (15) can thus be an eye opener in the unexplained cases. IEM may be associated with structural malformations.

a. Diffuse cortical migration and sulcation abnormalities are seen in Zellweger`s syndrome. b. Agenesis of the corpus callosum is seen in pyruvate decarboxylase deficiency, Menke’s disease and nonketotic hyperglycinaemia. c. Brainstem and cerebellar oedema are seen in Maple syrup urine disease. d. Subdural haematomas and frontotemporal atrophy suggest Glutaric aciduria. e. Hunter’s disease is a rare, X-linked mucopolysaccharidosis and it shows (16) perivascular space enlargement, subarachnoid space enlargement, IIIrd ventricle dilatation, pituitary sella abnormalities, cranial hyperostosis, craniosynostosis, enlarged cisterna magna, dens hypoplasia, periodontoid thickening, spinal stenosis, platyspondylia and disc abnormalities, which are frequently detected. f. 3-Methylglutaconic aciduria type I is a rare inborn error of leucine catabolism. MRI revealed (17) an extensive white matter disease in a 10 year old boy. The follow-up MRI in the 10-year-old boy, who presented earlier with isolated febrile seizures, showed mild abnormalities in the deep white matter.

5. M agnetic resonance spectroscopy (MRS): The in vivo MR spectroscopy findings are typical for selected IEMs.

a. The Adenylosuccinate lyase (18) (ADSL) deficiency is an inherited metabolic disorder which predominantly affects the central nervous system and manifests itself as seizures, muscular hypotonia, psychomotor delay and behaviouralabnormalities. There is a characteristic accumulation of succinyladenosine (S-Ado) in the tissue and in the body fluids. The in vivo proton MRS measurements show a prominent signal at the 8.3 ppm in the gray and white matter brain regions of all the patients, that corresponds to the accumulated S-Ado. b. MR spectroscopy (19) in Pyruvate dehydrogenase (PDH) deficiency shows an elevated level of pyruvate at the 2.37 ppm. In addition, the findings of MRI of the brain (20),(21),(22) that raise a suspicion, include complete or partial agenesis of the corpus callosum, heterotopic gray matter, the absence of the medullary pyramids and the abnormal inferior olives, hydrocephalus and cerebellar dysplasia. c. The diagnosis of Leigh`s Disease can be strongly suggested by neuro imaging, (23),(24),(25) which shows bilateral, symmetric, focal hyperintensities in the basal ganglia, the thalamus, the substantia nigra, and the brainstem nuclei at various levels on the T2-weighted MRI images (Table/Fig 10) due to spongiform changes and vacuolation in the affected brain structures. The underlying defect can be at any of the sites in the enzyme pathway for the respiratory metabolism, leading to lactate accumulation in body, which is demonstrated in MRI Spectroscopy [Table/Fig-11]. The image of the brain can be seen as a lactate peak. Although many conditions have a similar presentation, MRS offers valuable information for the individual patient for his/her diagnosis and therapy when it is integrated fully into the clinical setting (26). The various characteristic radiological findings can thus aid in reaching a proper and prompt diagnosis of these errors of metabolism for an effective treatment and to obtain baseline studies to monitor the disease (27). These findings that can cause terrors in the residents on the imaging studies of these patients, can in fact reduce the errors in diagnosing the inborn errors of metabolism and can at times be very conclusive when a paucity of the facilities and financial constraints prevent or delay the enzymology, histology and molecular studies.

Preventional Aspects 1) Genetic counselling and prenatal diagnosis: Most of the IEMs have a 25% recurrence risk, as they are inherited in an autosomal recessive manner. Therefore, when the diagnosis is known and confirmed in the index case, a prenatal diagnosis can be offered for the subsequent pregnancies (28). On such occasions, a radiological modality like ultrasound is a very useful guide for obtaining the samples of the chorionic villus tissue or the amniotic fluid, as is required for the diagnosis.

2) Neonatal screening: It should be offered in affording families who are known to have such a disease or in whom one sibling has such a disease. The population screening (29),(30) of the newborns as a form of preventive medicine, has attracted international interest due to the increased purchasing power of the middle classes3) In sporadic cases where the diagnosis has not been made and where the patient expires before the complete evaluation, it becomes difficult to perform an autopsy, as the parents may not be willing to go for it. In such cases, whole body MRI is useful in the investigation of some inherited metabolic causes of sudden infant death, like in the diagnosis of type 2 carnitine palmitoyltransferase deficiency, which might prevent future deaths in the family. It is a good alternative when autopsy has been refused (31).

Summary To satisfactorily tackle IEM, an integrated approach is needed. The modes of presentation and the clinical features are not always characteristic and bear a resemblance to the routine day to day illnesses. Radiological investigations play an important role in being the first to raise a strong suspicion and in some instances, even to confirm a clinical suspicion of IEM. Early clinical and laboratory diagnosis along with adequate treatment can provide these children a meaningful normal life. Hence, the medical fraternity needs to be aware of the role of radio-diagnosis is evaluating IEM.

in developing economies which are secondary to globalization, where it is strongly felt that that it is unfair to withhold the benefits of the first world medicine from infants in the under-privileged communities.

Key Message

Recent advances in Radio-diagnostic Imaging Sciences have enabled us to diagnose inborn errors of metabolism, not only during the intra-uterine state in high risk cases with known family history but also immediately after birth even before the clinical manifestations begin in unsuspected cases. Moreover giant strides in imaging are also throwing light on inborn errors of metabolism as the underlying cause of unexplained deaths by showing new ways of performing MR Spectroscopy based ‘Chemical Autopsy’ in cases where conventional disfiguring autopsy is rejected by the parents. No one can debate that conventional autopsy or necropsy remains the gold standard in unexplained deaths, but the high acceptance of virtuopsy (performed using CT scan or MRI) makes it an acceptable alternative when the former is declined.

References

1.
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2.
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