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Introduction

When all activities are harmonized, the organization will function better. Positive influencing of employees behaviour is important in this. Coordination therefore aims at stimulating motivation and discipline within the group dynamics. This requires clear communication and good leadership. Only through positive employee behaviour management can the intended objectives be achieved.

By verifying whether everything is going according to plan, the organization knows exactly whether the activities are carried out in conformity with the plan. Each of these steps is about solving problems in a creative manner. Finding a creative solution is often more difficult than discovering what the problem is, than making choices or the decision-making process.

It starts with creating an environmental analysis of the organization and it ends with evaluating the results of the implemented solution. The sixth function of Henri Fayol is mostly managerial. This include activities like planning, organising, commanding, coordinating and controlling. These first five functions of management are still important in organizations today. What do you think?

Has leadership changed on these points? If you liked this article, then please subscribe to our Free Newsletter for the latest posts on Management models and methods. How to cite this article: Van Vliet, V. Five Functions of Management Fayol. Did you find this article interesting? Your rating is more than welcome or share this article via Social media! Eliyahu Goldratt — was a lecturer, researcher, scientist and a business management guru.


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His scientific background began when he obtained a BSc. Degree from the University of Tel Aviv. Solid field research and a pragmatic approach to overcome those hindrances led to the book The Goal This book was later published by North River Press and it immediately became a best seller.

Eliyahu Goldratt developed many tools around that time and he was successfully employed by many multinational organizations. The aim was to teach organizations how to continuously improve and apply improvements. Eliyahu Goldratt. This article explains the Social Media Pyramid , in a practical way. After reading you will understand the basics of this powerful social media tool. To apply social media in your organization, start with monitoring; define your online image.

What has been written about my organization, brand, product or service? When you are, prepare to listen. Listening is more than just monitoring your online reputation, it is about preparing to take action. Responding or Commenting comes in many shapes and sizes.

Double Digit Growth - Michael Treacy

Often it is required to respond, but it can also be a wise choice not to respond. And do you have the resources necessary to handle all incoming requests? Monitoring can be defined as an N-to-1 relationship. For listening and responding you are dealing with an 1-on-1 relationship in which the sending and receiving change positions listening: organization is recipient, responding: organization is sender. After reading you will understand the basics of this powerful Six Sigma and problem solving tool. This cyclical problem solving model seeks to improve the processes within an organization.

The base of this problem solving tool is founded by Shingeo Shingo during the development of Poka Yoke. The problem is defined in this first step. Furthermore, it is important to recognize and define the following elements:. The purpose of this step is to establish the most important aspects of the current process and to collect relevant data. The following aspects are important in this:. Subsequently, the data that was collected in the previous step is analysed. The purpose of this step is to identify the root cause relationships.

The deeper causes of defects and errors are investigated. The current process is improved by using techniques and creative solutions. Brainstorming sessions can be a useful tool. Other, obvious solutions are:. This step does not only focus on control but on monitoring as well. Control ensures that any deviations can be corrected in the future. Monitoring leads to sustainable improvements and guarantees long-term success. Permanent monitoring is therefore required. To supplement the standard DMAIC Process, it is recommended to implement this step-by-step plan in other business processes as well.

By sharing experiences and new knowledge with other departments, changes can be effected more easily within the entire organization. It is important that employees have a good understanding of the usefulness of the procedure of the DMAIC process, that they discuss it with each other and that they are willing to share their experiences. Six Sigma was developed by Motorola and General Electrics to improve the quality of process outputs. This is done by identifying and removing the causes of errors.

This means it is can also be applied to one project. The strengths of this problem solving approach lie in the addressing and optimizing of the root causes in a process. For a creative change in which an organization changes course completely, however, the model is less applicable. The best results are achieved with a plan-led team approach. Let us look at a car garage with 50 locations who specialise in car tyres as an example. So far, in each branch, they have plenty of stock in various types of summer and winter tyres.

This enables them to quickly help the customer, delivering customer satisfaction and good word-of-mouth advertising. It now appears that the costs of the car company where very high last year. Management then decides to speak with all 50 branches in order to find out why. Together with all 50 branches, the biggest cost item is examined. Several different factors are then identified. Together with the 50 branches, management looks at methods for improvement. For example, they propose to work from a central warehouse, supplying the branches 3x per week.

Another option is to only have conventional tyres in stock while keeping specific tyre types in the central warehouse. The first solution is chosen unanimously. After a test period an evaluation takes place with all branches and management. It turns out that employees have to cancel a sale more often or only help customers after a few days. After evaluation, they examine the other solution they had at their disposal and decide to stock conventional tyres and have the rest delivered from the central warehouse. This solution will of course also undergo an evaluation period and full cost overview.

What is your experience? How to cite this article: Mulder, P. This article explains Responsibility Assignment Matrix in a practical way. After reading you will understand the basics of this powerful project management tool. This matrix is a structural chart in which is visually made clear what should be done by whom. In the matrix it is clear what the tasks and responsibilities are of each of the team members. Despite the simple nature of all information in the matrix memory, it can be very time-consuming to assign each member of the project team with the right tasks and responsibilities.

In addition the appropriate roles must be defined in advance before they are included in the responsibility assignment matrix. The Responsibility Assignment Matrix is also suitable for complex projects. By involving all the members of the project team in the development of the Responsibility Assignment Matrix, they will know exactly what is expected of them and they will participate and be more committed to using their own specializations. Moreover, the participants in the project will have a better understanding of what their joint participation in the project is. The role describes the participation with accompanying tasks of the individual in the project.

Such a role can be performed by several people in a group. Vice versa, one person may have several roles in the project. This is why several employees can have the role of project manager and one individual may have the role of manager and task performer.

Do you recognize the practical explanation or do you have more additions? What are your success factors for good stakeholder management during a project? After reading you will understand the basics of this powerful marketing and stakeholder management tool. It is important for companies to build up a good relationship with their customers.

Customer Relationship Management helps companies to gain an insight into their customers and their buying behaviour.

It engages in the application and use of technology to promote the relationship with new and current customers. All information that is related to potential customers is recorded within Customer Relationship Management.

Empowerment Through Knowledge

By using this methodology, a company can increase sales and therefore profitability and reduce operational costs. It is important that CRM runs on a software system in which departments have good contacts with each other and these can deliver an added value to the customer relationship management. Contact management is of the utmost importance; monitoring and registration of interaction and communication with all customers. Furthermore, all stages of the sales process must be streamlined and it must be possible to automatically enter customer data into the system.

As a result, potential customers will be monitored from their first contact until the final order and their buying behaviour will be updated. A good CRM system is indispensable for the marketing department; who are the best customers, what do they buy and what do the potential customers look like?

The so-called multi-channel campaigns such as e-mail, social media and direct mail help measure how many leads and deals are generated. Depending on these data, sales prognoses and turnovers can be calculated. Through this predictive analysis customers and target groups can be segmented better as a result of which marketing campaigns can be tailored to the customers demands. Although customer service mainly focuses on helping customers, it is also a source to document customer experience.

A good system encourages cooperation between various departments such as sales, customer service and marketing. The common objective is to share as much information as possible so that the customer can be serviced even better. A marketeer can therefore respond to a product demand of a customer. A well-integrated system will prevent different departments from contacting the customer with the same information. A central application will make customer contact easier and saves time. In addition, information must be extracted and collected from several sources and they must be integrated in a comprehensive system.

Customers use social media more and more often to voice their opinions or share the experiences about companies, products and services. Sometimes this has far-reaching and major consequences for companies. This is why companies want to take part in the dialogue via social media to influence their customers. This makes it possible to identify various customer groups, improve customer retention and adjust product supply. Customer privacy must always be taken into consideration.

When customers do not give their permission to divulge information, data security is required. What are your success factors for the good customer or stakeholder management system? After reading you will understand the basics of this powerful strategy tool. Eliyahu Goldratt assumed that the ultimate goal of most organizations is to make a profit and other goals are derived from this goal. He indicated that it is especially the constraints that prevent organizations from generating maximum profits. Every organization has at least one constraint.

On the one hand theory of constraints, also known as the thinking processes , focuses on how quickly results can be achieved. This is the rate at which an organization generates money through sales. This consists of the investments in assets of an organization, that can be quickly converted into liquid assets. This is the money that has been invested to turn inventory into throughput such as labour costs, material costs and depreciations.

The management philosophy theory of constraints can be practically executed. The weakest link in an organization is identified whereupon it must be decided whether its causes are physical or policy-related. Should these actions not lead to an increase, it is considered advisable to abandon the breakthrough of this constraint.

It is wise to make an assessment in between steps 3 and 4, to establish whether performance is still being hindered by this earlier constraint. This could involve changes in the existing system reorganization , increase of sales or changes in the market. Such adjustments require investments and will only be deployed after all other options have been considered. After the implementation of the opted solution and after elimination or breakthrough of the constraint, the process starts over again from step 1.

On the one hand the impact of the implemented solution is looked at and on the other hand new constraints are identified and broken through. Constraints can be an internal and an external part of an organization. Internal constraints present themselves when there is too little output to meet the demands in the market. By identifying and reinforcing this constraint, a breakthrough is thus realized. Examples of such constraints are badly deployed production methods, lack of competent employees and bad policies as a result of which a system cannot function optimally.

External constraints indicate a too large output with respect to the demand in the market. Sep 12, Payal Sinha rated it it was amazing. Quiet in 30 Minutes- an Eye Opener I simply loved this book both for its compactness and its in-depth content. In a fast moving world where people have a small amount of time to read an entire book, it is really helpful to come across shortened versions of bestsellers and benefit from all their information.

The book is all about introverts and how they make a success of their lives. It is not made up of just bare facts but sums up the lives of some highly influential people from History such as Mahatma Gandhi, Bill Gates and Eleanor Roosevelt. The book reveals how the introvert nature of these personalities helped them reach the pinnacles of success. Introverts possess a number of qualities lacking in extroverts.

So, while looking for a balanced personality, we should in fact cherish introverts and applaud their merits. This book is a must read for all people who are actually introverts or connected to some introvert in their real lives. Oct 05, Keri rated it it was amazing.

This book was written by a successful lawyer who felt the need to explain who and what introverts are and how society can benefit from them. The book explains the major differences in extroverts and introverts and how society looks favorably on extroverts; however, introverts tend to be deep and careful thinkers. The book explains how extroverts and introverts working together can be very beneficial to society.

Extroverts and introverts can complement each other if everyone involved understands their roles. The book concludes with some great advice on helping introverts become successful and vital role models in society. Oct 04, Kevin S. A valuable and must have companion to an important book By Kevin S. This concise summary guide is a most worthy and valuable resource and inspires the reader to want to read, and receive the impact of, the full length book. Sep 24, Kaleigh Carter rated it really liked it. This guide would be a useful way for introverts to gain a deeper understanding and acceptance of their own personality traits.

Parents, partners, coworkers, and bosses of introverts will find this summary useful as a quick way to gain insight into the minds of an introvert. Mar 12, Rowan rated it really liked it. The full book gets 5 stars, it adds so much :- I enjoyed this quick study guide version. It reduces and summarizes the important and helpful concepts without losing the effectiveness. Prefer to recommend the full version of the book but this is a little gem is filled with priceless knowledge and strategies well worth 30 min!!

Sep 12, Gg rated it really liked it. I was fascinated by Chapter 4,detailing the genetic and environmental factors that contribute to temperament, and found Chapter 10, regarding the communication differences between introverts and extroverts, particularly useful. I now better understand the thinking, reasoning, and behaviors of introverts, and have already applied my new knowledge at my most recent staff meeting!

Also, as an avid reader with very little free time, I was pleased to find this streamlined book was still packed full of credible data, interesting facts and anecdotes, and relatable references. Oct 16, Chester rated it it was amazing. You know. One of these days. Oct 24, N Sullivan rated it it was amazing. I had no idea of the advantages I have in everyday life, as a result of a unfairly extrovert-dominated society!

Eye-opening, instructive, and invigorating, this book is a must-read for anyone planning to interact successfully in the world with colleagues, friends, managers, and more. Oct 15, SM Tolhurst rated it really liked it. Has American culture completely dismissed the greatness of our introverts, despite the success stories of Bill Gates and Warren Buffet? Oct 10, Beryl rated it it was amazing. We are invited into a world that can still a place within each of us, whether or not silence is our natural milieu.

This work reminds us that extroverts and introverts are not diametrically opposed, rather two parts of the same equation. At our cores, we are who we are, but looking over the fence to who we are not might uncork some creative approaches. We all need quiet, but some of us need a little reminder to seek out our own solitude; this book may serve as the prompt to carve out some time to slow down and seek out a slice of our own silence. Oct 08, Grace Woo rated it really liked it.

This book is a summary of Susan Cain's longer book - and succinctly explains character traits of introverts, including how they might be judged passive, weak, etc , and how those assumptions have been historically wrong. As a shy person, I'm glad to find a book that highlights what is wrong with how we've been traditionally been taught to behave. One doesn't need to be raging with charisma, outgoing mannerisms, and public speaking capabilities to be successful.

The more quiet, thoughtful way ca This book is a summary of Susan Cain's longer book - and succinctly explains character traits of introverts, including how they might be judged passive, weak, etc , and how those assumptions have been historically wrong. The more quiet, thoughtful way can lead to success too, e. Sep 05, Pam rated it really liked it.

Cain sheds light on introverts and their importance to modern society. She also calls attention to parents, guardians, teachers, etc. The cultural parallels American v. Oct 23, David Morris rated it it was amazing Shelves: reviewed. Oct 22, Agod rated it it was amazing. This book not only calls attention to a problem in how we operate as a society, but offers solutions on a personal level.

It gives advice on how to communicate between extroverts and introverts, how to foster introverts creativity, and how to take care of you first, before conforming to social expectations. Oct 18, Chris Treacy rated it it was amazing. And yet, despite the focus on alpha personalities, Cain demonstrates that introverted thinkers likely hold some of our most valid, well-thought-out ideas… but we seldom get to hear them through the din of the outspoken front-line.

Oct 25, Mavis rated it it was amazing. This book exceeded expectations. The level of insight was amazing and I came away from the book feeling like I understood myself a little better, and learned some key tools in having a more healthy perspective. It is very informative. Five out of Five stars and I definitely recommend it. Note: In states with an expanded newborn screening program, isolated methylmalonic acidemia can be diagnosed in well-appearing newborns prior to an episode of acute decompensation. In older infants and children: failure to thrive, renal syndromes and hypotonia, intellectual disability or other acute basal ganglia stroke and chronic neurologic symptoms.

Isolated renal tubular acidosis or chronic renal failure [ Dudley et al , Coman et al ]. Metabolic stroke of the basal ganglia [ Korf et al , Heidenreich et al ]. Establishing the Diagnosis An overview of the process of intracellular propionate and cobalamin metabolism is depicted in Figure 1. Figure 2. High anion gap metabolic acidosis in arterial or venous blood gas testing and huge quantities of ketone bodies and lactate in the urine.

Table 1. Tiered single- gene testing. Because the phenotype of isolated methylmalonic acidemia can be identical regardless of the mutated gene, molecular genetic testing can be performed in the following order:. Use of a multigene panel that includes these five genes and other genes in the metabolic pathway see Differential Diagnosis. Note: The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.

Table 2. Worgan et al []. Stucki et al []. Elevated C4-dicarboxylic acylcarnitine C4DC is a marker for both methylmalonylcarnitine and succinylcarnitine, and can indicate methylmalonic aciduria associated with succinyl-CoA ligase deficiency [ Fowler et al , Morava et al ]. Clinical Characteristics Clinical Description The phenotypes of isolated methylmalonic acidemia described below that are associated with the mut 0 enzymatic subtype, mut — enzymatic subtype, cblA , cblB , and cblD -MMA share clinical presentations and a natural history characterized by periods of relative health and intermittent metabolic decompensation, usually associated with intercurrent infections and stress [ Zwickler et al ].

Thrombocytopenia and neutropenia, suggestive of neonatal sepsis, can be seen. The major secondary complications include: Intellectual disability. Intellectual disability may or may not be present even in those with severe disease. The age of disease onset, the presence of severe hyperammonemia at diagnosis, and a history of seizures were associated with more severe impairments [ O'Shea et al ]. Tubulointerstitial nephritis with progressive impairment of renal function. All individuals with isolated methylmalonic acidemia, even those who are mildly affected or who have received a liver allograft [ Nyhan et al ], are at risk of developing renal insufficiency [ Walter et al , Kruszka et al ].

Secondary mitochondrial dysfunction rather than direct nephrotoxicity of methylmalonic acid is hypothesized. An acute renal syndrome, seen in the setting of metabolic decompensation, may also exist [ Stokke et al ] and requires further clinical delineation. Moreover, renal tubular dysfunction presenting as a decrease in urine concentrating ability and acidification, hyporeninemic hypoaldosteronism, tubular acidosis type 4, and hyperkalemia have been reported in a number of affected individuals, and are supported by murine studies [ Walter et al , D'Angio et al , Pela et al , Manoli et al ].

Neurologic findings. Some individuals develop a "metabolic stroke" or infarction of the basal ganglia characteristically the globus pallidus externa during acute metabolic decompensation, which can produce an incapacitating movement disorder [ Korf et al , Heidenreich et al ]. Distinct segments of the globus pallidus and sometimes the substrantia nigra in the cerebral peduncles are affected , suggesting a non-uniform, cell-specific sensitivity to the mechanism of infarct [ Baker et al ].

Delayed myelination, incomplete opercularization, subcortical white matter changes, and brain stem and cerebellar changes have been described [ Harting et al , Radmanesh et al ]. The incidence of pancreatitis in isolated methylmalonic acidemia is unknown, but it is a well-recognized complication [ Kahler et al ]. It can occur acutely or chronically. Pancreatitis may be under-recognized because it can manifest nonspecifically with vomiting and abdominal pain.

Growth failure. Growth failure is frequent and multifactorial. It is the result of severe chronic illness and perhaps relative protein malnutrition that is complicated further by chronic renal failure. Many infants are less than three standard deviations below normal for both length and weight. Some children have documented growth hormone GH deficiency, but response to GH therapy may vary see Management. Functional immune impairment. This results in an increased susceptibility to severe infections, particularly by fungal and gram-negative organisms [ Oberholzer et al , Wong et al ].

Bone marrow failure. Optic nerve atrophy. Late-onset optic atrophy associated with acute visual loss, resembling the presentation of the mitochondrial disorder Leber hereditary optic neuropathy LHON , has been reported in isolated methylmalonic acidemia [ Wasserstein et al , Williams et al , Pinar-Sueiro et al , Traber et al ], as well as in propionic acidemia [ Williams et al , Martinez Alvarez et al ].

Isolated instances of hepatoblastoma have been reported in the native or donor liver in individuals with mut MMA; however, the overall incidence of cancer in these patients is unknown [ Cosson et al , Chan et al ]. Genotype-Phenotype Correlations Precise genotype-phenotype correlations are difficult to determine since most affected individuals are compound heterozygotes. Prevalence Several studies have estimated the birth prevalence of isolated methylmalonic acidemia [ Sniderman et al ].

Differential Diagnosis Atypical methylmalonic acidemia is associated with increased, usually mild urinary excretion of methylmalonate. The following are included in this group of disorders: Cobalamin C deficiency cblC is perhaps the most common inborn error of intracellular cobalamin metabolism. Individuals with this disorder almost always have increased plasma concentrations of homocysteine and methylmalonic acid, with low levels of methionine, and historically a highly variable age of onset.

Affected individuals frequently have developmental delay and develop a pigmentary retinopathy and a "bull's eye" maculopathy. The pathogenic variant c. Deficiencies of complementation groups cblD , cblF , and cblJ are extremely rare autosomal recessive disorders. The location and nature of the pathogenic variant therefore determines whether a patient will display methylmalonic aciduria, homocystinuria, or both metabolic abnormalities:. The cblD- methylmalonic aciduria subtype cblD -MMA previously known as cblD- variant 2 is caused by pathogenic nonsense and frame-shifting variants in exons 3 and 4;.

The cblD- homocystinuria subtype previously known as cblD variant 1 is caused by pathogenic missense variants in exons ;. A cblD- combined subtype cblD that features elevations of both MMA and homocysteine is caused by frame-shifting pathogenic variants in exon 5, exon 8, and intron 7. It is important to note that several individuals with cblF or cblJ can have decreased serum vitamin B 12 levels, suggesting a role for the lysosome in intestinal uptake of ingested cobalamin.

All described affected males to date had MMAemia and MMAuria, and most, when studied, displayed combined hyperhomocystinuria and methylmalonic acidemia. The clinical phenotype features intractable epilepsy and profound neurocognitive impairment without the specific bull's-eye maculopathy of cblC deficiency [ Yu et al ]; however, the phenotype needs further characterization.

Benign methylmalonic acidemia with distal renal tubular acidosis one sibship [ Dudley et al ]. Malonyl-CoA decarboxylase deficiency, usually associated with combined methylmalonic and malonic aciduria, with significantly higher malonic versus methylmalonic acid levels [ Brown et al ]. Isolated methylmalonic aciduria and normal plasma concentrations of methylmalonic acidemia 2 families [ Sewell et al , Martens et al ].

If possible, measurement of plasma concentrations of methylmalonic acid, methylcitrate, free and total carnitine, and an acylcarnitine profile to document propionylcarnitine C3 species concentration. Measurement of serum vitamin B 12 concentration to determine if a nutritional deficiency is present in the patient and possibly the mother in newborns.

Treatment of Manifestations No consensus exists among various metabolic centers regarding treatment of acute and chronic complications of methylmalonic acidemia. Stabilization of critically ill individuals Volume replacement with isotonic solutions. All IV solutions should contain glucose, preferably D 10 or D If hyperglycemia develops, an insulin infusion may be needed. The total base deficit should be followed serially with repeat electrolyte and venous or arterial blood gas measurements and corrected by hydration and bicarbonate replacement, as needed [ Baumgartner et al ].

Adequate kcals must be delivered. Central or peripheral total parenteral nutrition TPN , which typically contains glucose and amino acids, and in some instances, lipids, may be required. Total protein administration is usually completely withdrawn for no more than hours and reinstated gradually depending on the patient's acid-base balance and remaining test values, including ammonia, lactic acid, and plasma amino acids among others.

Dietary protein should be reintroduced enterally as soon as is feasible given the clinical scenario and may need to be further augmented with TPN. Nasograstric or orogastric feeding should be strongly considered so that enteral feedings can be reintroduced without delay. NCG allosterically activates CPS1 carbamyl phosphate synthetase 1 , the first step of the urea cycle. It has been effective in normalizing the blood ammonia concentration in patients with a deficiency of NAGS N-acetylglutamate synthase and can also benefit some patients with propionic and possibly methylmalonic acidemia [ Tuchman et al , Ah Mew et al ].

The underlying biochemical parameters and the frequency of metabolic decompensation improved significantly in individuals undergoing liver transplantation despite persistent metabolic abnormalities [ Nyhan et al , Kaplan et al , Niemi et al ], probably as a result of increased extrahepatorenal methylmalonic acid production primarily from the skeletal muscle [ Chandler et al ]. Following liver transplantation, some individuals continued to have progressive renal failure as well as high CSF concentrations of methylmalonic acid [ Nyhan et al , Kaplan et al ].

Neurologic complications post-transplant, including globus pallidus injuries [ Chakrapani et al , Cosson et al , McGuire et al ] suggest that adequate protein restriction and supportive care should be continued after the transplantation. Earlier transplantation particularly for individuals with mut 0 who are very fragile is gaining support as surgery techniques and outcomes improve [ Niemi et al , Spada et al ].

The choice of the kind and timing of the indicated transplant procedure remains challenging for families and treating physicians [ Sloan et al ]. In the long term, the details regarding development of renal disease, optic nerve atrophy, and neurologic complications will be most important.

Books for Readers # 183

Prevention of Secondary Complications Frequent monitoring of plasma amino acids is necessary to avoid deficiencies of essential amino acids particularly isoleucine, valine, and methionine as a result of excessive protein restriction and the development of acrodermatitis-enteropathica-like cutaneous lesions in methylmalonic aciduria, as in other organic acidurias glutaric aciduria-I and amino acid disorders maple syrup urine disease [ De Raeve et al ].

Surveillance During the first year of life, infants may need to be evaluated as frequently as every week. The following should be monitored on a regular six-month to one-year basis or more frequently if the patient is unstable and requires frequent changes in management: Plasma amino acids.

Supplementation with the individual propiogenic amino acids valine and isoleucine, as they directly increase the toxic metabolite load in patients with disordered propionate oxidation [ Nyhan et al , Hauser et al , Manoli et al b ]. Evaluation of Relatives at Risk Depending on the genotype and phenotype of the proband , evaluation of sibs at risk should be performed using biochemical testing with treatment instituted as soon as possible if a sib is affected.

Pregnancy Management Oral and intramuscular vitamin B 12 has been administered to women pregnant with a fetus with vitamin B 12 -responsive MMA, resulting in decreased maternal MMA urine output [ Ampola et al , van der Meer et al ]. Therapies Under Investigation Carefully designed clinical studies are required to evaluate the efficacy of antioxidant regimens in patients with MMA. Genetic Counseling Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions.

Mode of Inheritance Isolated methylmalonic acidemia complete or partial deficiency of the enzyme methylmalonyl-CoA mutase; defect in transport or synthesis of the methylmalonyl-CoA mutase cofactor, adenosyl-cobalamin; and deficiency of the enzyme methylmalonyl-CoA epimerase is inherited in an autosomal recessive manner. Related Genetic Counseling Issues See Management, Evaluation of Relatives at Risk for information on testing at-risk relatives for the purpose of early diagnosis and treatment. Family planning The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.

It is appropriate to offer genetic counseling including discussion of potential risks to offspring and reproductive options to young adults who are affected , are carriers, or are at risk of being carriers. Note: Due to the limited availability and longer turnaround time for cellular biochemical assays, the preferred method for prenatal diagnosis is molecular genetic testing. The use of fetal cell-free DNA in maternal plasma [ Gu et al ].

Biochemical testing. Historically both amniotic fluid measurements and cellular biochemical assays were used:. Amniotic fluid analysis of methylmalonic acid. The absolute positive predictive and negative predictive values of metabolite analysis only have yet to be determined. Elevation of metabolites below the range of affected fetuses can indicate a heterozygous status and should therefore be followed by confirmatory testing in cell studies.

Incorporation of 14 C propionate and complementation assay of cultured fetal cells obtained by amniocentesis usually performed at approximately 15 to 18 weeks' gestation or chorionic villus sampling CVS at approximately ten to 12 weeks' gestation. Studies on chorionic villus cells can be false negative and should be followed up by studies on cultured amniocytes [ Morel et al ]. Confirmation of the diagnosis by the same assay in an affected family member must be obtained before prenatal testing can be performed.

Note: For pregnant women not interested in pursuing prenatal diagnosis by amniocentesis or CVS, a urine organic acid test may be helpful since women carrying an affected fetus have been shown to excrete MMA in their urine [ Ampola et al , van der Meer et al ]. My46 Trait Profile. Methylmalonic acidemia. Table A. Isolated Methylmalonic Acidemia: Genes and Databases. Table B. Table 3. Trp54Ter c. Leu89Pro c. Gln95Ter c.

GlnTer c. GlyArg c. LeuTer c. GlyGlu c. ArgTer c. ArgGln c. Table 4. AlaThr c. ArgCys c. ArgHis c. ArgTrp c. TyrCys c. Table 5. Gln18Ter mut 0 c. Arg31Ter mut 0 c. Arg93His mut 0 c. Pro95Arg mut 0 c. TrpArg mut 0 c. ArgCys mut 0 c. PheSer mut 0 c. AlaGlu mut 0 c. GlyArg mut 0 c. GlySer mut 0 c. AsnTyr mut 0 c. GlyVal mut 0 c. ArgHis mut 0 c. GlyAsp mut 0 c. GlyArg mut — c. TyrCys mut — c. TyrAsn mut — c. AsnSer mut 0 c. LeuPro mut 0 c. LeuArg mut — c.

Take Command of Your Growth

ArgTrp mut — c. MetLys mut — c. Table 6. Lys60Gln c. Table 7. Leu21IlefsTer2 Leu20fsTer21 c. Arg45GlyfsTer15 c. Arg54Ter c. Asn77GlufsTer5 c. CysMetfsTer10 ThrfsTer Variant designation that does not conform to current naming conventions. Isodisomy of chromosome 6 in a newborn with methylmalonic acidemia and agenesis of pancreatic beta cells causing diabetes mellitus. J Clin Invest. NY, a new frequent mutation among mut o forms of methylmalonic acidemia in Caucasian patients. Eur J Hum Genet. Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut o and mut- forms of methylmalonic acidemia: identification of 29 novel mutations in the MUT gene.

Hum Mutat. A common mutation among blacks with mut- methylmalonic aciduria. N-carbamylglutamate augments ureagenesis and reduces ammonia and glutamine in propionic acidemia. Combined malonic and methylmalonic aciduria: exome sequencing reveals mutations in the ACSF3 gene in patients with a non-classic phenotype.

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J Med Genet. Growth hormone deficiency associated with methylmalonic acidemia. J Pediatr Endocrinol Metab. Prenatal therapy of a patient with vitamin-Bresponsive methylmalonic acidemia. N Engl J Med. Inherited disorders affecting mitochondrial function are associated with glutathione deficiency and hypocitrullinemia. Use of human somatotrophin in the treatment of a patient with methylmalonic aciduria.

Eur J Pediatr. MRI characteristics of globus pallidus infarcts in isolated methylmalonic acidemia. Baumgarter ER, Viardot C. Long-term follow-up of 77 patients with isolated methylmalonic acidaemia. J Inherit Metab Dis. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet J Rare Dis. Renal transplantation in 4 patients with methylmalonic aciduria: a cell therapy for metabolic disease. Mol Genet Metab. Malonyl coenzyme A decarboxylase deficiency. Liver-directed recombinant adeno-associated viral gene delivery rescues a lethal mouse model of methylmalonic acidemia and provides long-term phenotypic correction.

Hum Gene Ther. SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness. Celiker MY, Chawla A. Congenital B12 deficiency following maternal gastric bypass. J Perinatol. Rapid diagnosis of methylmalonic and propionic acidemias: quantitative tandem mass spectrometric analysis of propionylcarnitine in filter-paper blood specimens obtained from newborns. Clin Chem. Metabolic stroke in methylmalonic acidemia five years after liver transplantation. J Pediatr. Molecular characterization of methylmalonate semialdehyde dehydrogenase deficiency.

Hepatoblastoma in a patient with methylmalonic aciduria. Am J Med Genet A. Metabolic phenotype of methylmalonic acidemia in mice and humans: the role of skeletal muscle. BMC Med Genet. Adenovirus-mediated gene delivery rescues a neonatal lethal murine model of mut 0 methylmalonic acidemia.

Long-term rescue of a lethal murine model of methylmalonic acidemia using adeno-associated viral gene therapy. Mol Ther. Mitochondrial dysfunction in mut methylmalonic acidemia. Metabolic disorders mimicking Reye's syndrome. J Formos Med Assoc. Lethal late onset cblB methylmalonic aciduria. Crit Care Med. Renal transplantation in a boy with methylmalonic acidaemia. Nat Genet. Gene identification for the cblD defect of vitamin B12 metabolism. Renal transplantation in a year-old girl with vitamin Bresponsive cblA-type methylmalonic acidaemia.

Pediatr Nephrol. Massachusetts Metabolic Disorders Screening Program. Methylmalonic aciduria. Cloning and expression of a mutant methylmalonyl coenzyme A mutase with altered cobalamin affinity that causes mut- methylmalonic aciduria. Clustering of mutations in methylmalonyl CoA mutase associated with mut- methylmalonic acidemia. Am J Hum Genet. Renal tubular dysfunction in methylmalonic acidaemia. Methylmalonic and propionic acidaemias: management and outcome.

Multiple OXPHOS deficiency in the liver, kidney, heart and skeletal muscle of patients with methylmalonic aciduria and propionic aciduria. Pediatr Res. Acrodermatitis enteropathica-like cutaneous lesions in organic aciduria. Successful pregnancy in a woman with mut- methylmalonic acidaemia. National academy of clinical biochemistry laboratory medicine practice guidelines: follow-up testing for metabolic disease identified by expanded newborn screening using tandem mass spectrometry; executive summary.

Identification of the gene responsible for the cblB complementation group of vitamin Bdependent methylmalonic aciduria. Hum Mol Genet.