Maple Syrup Urine Disease (MSUD) is an autosomal recessive metabolic disorder. MSUD is a rare disorder that occurs in about 1 out of every 185,000 births worldwide. The baby receives two copies of the altered genes – one from the mother and one from father in which the body is unable to breakdown amino acids – Leucine, Isoleucine and Valine. This results in a buildup of harmful substances in the blood and urine. One of the main characteristics of this disorder is sweet-smelling urine, hence the name, MSUD. This disorder is also known as BCKDC deficiency, branched-chain alpha-keto acid dehydrogenase deficiency.
MSUD – TYPES
Maple syrup urine disease (MSUD) is categorized as classic (severe), intermediate, intermittent and thiamine responsive.
CLASSIC: This is the most common and severe form of this disorder and generally present in new-borns. The symptoms such as poor feeding, increased lethargy and irritability are present within a few days of birth. The onset is usually triggered when the infant’s body begins to process protein from feedings.
INTERMEDIATE: This is a rare type of MSUD. The symptoms are similar to classic MSUD but the age of onset varies greatly. This disorder is diagnosed between 5 months & 7 years. Children with this type of MSUD have a higher level of enzyme activity than classic MSUD.
INTERMITTENT: The symptoms usually do not appear until a child is between 1 and 2 years of age. It’s a milder form of classic MSUD and children can tolerate normal protein levels in the diet. The children with intermittent MSUD have significant enzyme activity — about 8 to 15 percent higher than normal activity. The initial onset happens when the child experiences stress, illness, or an unusual increase in protein.
THIAMINE RESPONSIVE: This rare form of the condition is responsive to large doses of thiamine, or vitamin B-1 which improves enzyme activity. Symptoms usually occur after infancy.
SCREENING, SIGNS & SYMPTOMS
Every baby is screened to detect 1 of 9 rare conditions and to avoid any serious complications. The newborn blood spot screening is also known as the heel prick test. The symptoms of this disorder are sweet-smelling urine/sweat with maple syrup odor, weight loss, loss of appetite, breathing difficulties, lethargy, vomiting, irritability, shrill cry, seizures, loss of consciousness, irregular respiration, apnea, ear wax, etc. 
Children diagnosed with MSUD are given a low protein diet to reduce the amount of amino acids. Some children may need to take supplements of isoleucine and valine.
LIVER TRANSPLANT CASE STUDIES
In 1997, liver transplantation was reported in a child with MSUD who had developed acute liver failure. The liver transplant was successful and the previously diagnosed MSUD was metabolically cured. The MSUD transplant protocol has been adopted with high success rates with normalisation of amino acid profiles within a few hours after transplant and continuing to remain so despite advancing to a regular diet of unrestricted protein.
- Maple Syrup Urine Disease (MSUD) | Cleveland Clinic. (2019). Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/21168-maple-syrup-urine-disease
- Strauss, K. A., Puffenberger, E. G., & D Holmes Morton. (2013, May 9). Maple Syrup Urine Disease. Nih.gov; University of Washington, Seattle. https://www.ncbi.nlm.nih.gov/books/NBK1319/
- Maple syrup urine disease. (2017, October 19). Nhs.uk. https://www.nhs.uk/conditions/maple-syrup-urine-disease/
- Giorgi, A. (2016, October 11). Maple Syrup Urine Disease (MSUD). Healthline; Healthline Media. https://www.healthline.com/health/maple-syrup-urine-disease#types
- George V., M. (2019). Pediatric Maple Syrup Urine Disease | Children’s Pittsburgh. Children’s Hospital of Pittsburgh. https://www.chp.edu/our-services/transplant/liver/education/liver-disease-states/maple-syrup-urine-disease
The cornerstone of nutrition therapy for Phenylketonuria has been limiting the consumption of Phenylalanine to avoid accumulation in the blood.
This concept of limiting phenylalanine in the diet was first demonstrated in early 1950’s, as it had a positive impact on the behaviour in a young patient with PKU. Specialized amino acid based formula with low phenylalanine made dietary treatment for these patients possible. Although earlier it was believed that formula should be given only for 6 years, later data indicated that “diet for life” is the optimal mode of treatment.
Despite these significant results in behaviour, cognitive deficits were found in poorly managed individuals going to adulthood. Compliance for strict regimen among PKU individuals was found to be difficult which led to undesirable clinical outcomes.
Different approaches in nutrition management were explored such as glycomacropeptide protein-based medical foods and large neutral amino acids. Here we elaborate on Large Neutral Amino Acids.
What are Large Neutral Amino Acids?
LAT-1 transporter helps these amino acids pass the blood brain barrier.
In an individual with PKU due to the absence of enzyme Phenylalanine hydroxylase (PAH) & tetra hydrobiopterin (BH4), phenylalanine does not get metabolised to tyrosine, which thus gets accumulated in the liver and results in increased levels in the blood. Phenylalanine passes the blood-brain barrier with the help of LAT 1 transporter which leads to cognitive deficits, neurophysiological & neuropsychological dysfunction.
Supplementation of LNAA increases the levels in the brain and reduces the concentration of Phenylalanine as they compete with LAT1 transporter for crossing the blood-brain barrier. This was suggested 40 years ago while experimenting on artificially induced hyperphenylalaninemic rats. The successful lowering of phenylalanine levels in the brain led to further research in this area. Data suggests that various combinations of LNAA were tried depending upon the treatment goal.
LNAA treatment goal – to decrease cerebral Phenylalanine concentration
- LNAA supplementation:
- Increases the levels in the plasma thus competing with Phe for uptake at the blood-brain barrier. The concentration of Phe in the brain was decreased by 20 % when studied in humans. (Moats, 2003)
- Increases branched amino acids like isoleucine, valine and leucine concentration in the brain showing improvement in verbal ability, cognitive functions and protein synthesis in the brain (Moats, 2003)
- Improves neurotransmitter synthesis serotonin and dopamine known as feel good chemicals depending upon the concentration of tyrosine and tryptophan in the brain. Although, reports find deficiency of tyrosine in the brain, thus indicating higher concentration of the tyrosine in LNAA supplementation (van Spronsen FJ, 2010)
LNAA supplementation to decrease blood phenylalanine concentration
- LNAA supplementation in PKU mice had shown reduction of Phe by 47-63.5 % (Matalon, 2006).
- It is hypothesized that due to supplementation of LNAA there is competition of Phe for uptake from GI tract into the blood (van Spronsen FJ, 2010)
- Reports suggest that, the availability of high concentration of essential amino acid in the blood results in Phe utilization for protein synthesis. This leads to decrease in Phe in the blood (Danique van Vilet, 2015)
LNAA is seen as an alternative to conventional dietary therapy in PKU treatment especially for individuals, like adolescents and adults, who have uncontrolled phenylalanine levels. The concentration of LNAA supplementation depends upon different treatment strategies.
Methylmalonic acidemia (MMA) is a rare genetic disorder with an incidence of one in 50,000 live births, affecting males and females from all demographics. MMA was first identified in 1967. In MMA, the body is unable to break down certain amino acids namely methionine, threonine, isoleucine and valine which leads to the inability in properly digesting specific fats and proteins, leading to build up of a toxic level of methylmalonic acid in blood and disrupts the normal amino acid metabolism. Symptoms of MMA include poor feeding, vomiting, trouble in breathing, and lethargy. [1,2]
MMA AND GENETICS
Methylmalonic acidemia is inherited in an autosomal recessive pattern. In MMA, one copy of the altered gene is inherited from the mother and the other copy of the altered gene is inherited from the father. Therefore, each parent of an affected child has one copy of the gene that is altered and one that is unaltered. Parents are called “carriers”. Carriers are asymptomatic. MMA is a major concern in countries such as Palestine where immediate family members often marry and have children that inherit MMA at a much higher prevalence than neonates in western countries.
TYPES OF MMA
There are different types of MMA. The types of MMA which can be treated with vitamin B12 injections are called ‘vitamin B12 responsive.’ The other type, called ‘MMA with homocystinuria’ occurs when special enzymes which change vitamin B12 into a form that the body can use is either missing or not working properly. As a result homocystine, methylmalonic acid, and other harmful substances build up in the blood.
HOW IS MMA DIAGNOSED?
MMA is diagnosed at birth through newborn screening – a simple heel stick blood sample at birth used to check for numerous diseases. MMA is typically confirmed when proteins are introduced in the infant’s diet. The presence of MMA can also be suspected through the use of a CT or MRI scan or ammonia test. Elevated levels of ammonia, glycine, and ketone bodies may also be present in the blood and urine. However, these tests are by no means specific and require clinical and metabolic/correlation.
Additional tests for MMA diagnosis include:
- Biochemical testing for abnormal levels of specific chemicals
- Testing for responsiveness to vitamin B12
- Genetic testing for mutations in one of the genes associated with methylmalonic acidemia.
One such case is of a child from Children’s Hospital of Philadelphia. In less than 24 hours of being brought home, the baby had trouble eating and breathing. The baby was unable to open his eyes and the arms would flop. The temperature was critically low and neonatologists found dangerously high levels of ammonia in his system. MMA was diagnosed through newborn screening. His condition was treated through medications and a special diet low in protein.
MMA- NUTRITIONAL INTERVENTIONS & OTHER TREATMENTS
Currently, one of the main treatment is a diet low in the amino acids leucine, valine, methionine, and threonine with limited amounts of protein. There are also specially formulated foods such as special low-protein flours, pastas, rice and snacks such as biscuits that are made especially for children with organic acid disorders.
A liver transplant or a combination kidney-liver transplant is another alternative treatment used to treat MMA when repeated metabolic decompensation cannot be relieved by medication or nutrition therapy. Transplantation helps to prevent metabolic crises, lowers plasma and MMA levels in the urine, and also enhances overall quality of life. Even though the surgery is known to be lifesaving, it does not totally cure the disorder. Majority of the patients still maintain a low protein diet even after the surgery.
MMA- GENETIC THERAPY
On May 29, 2021, a 9-year-old patient, Eddie Axelson, of Monroe Carell Jr. Children’s Hospital at Vanderbilt was the first in the world to receive an investigational gene editing therapy for MMA. Axelson received the dose of hLB-001, administered via IV infusion. In gene editing therapy, a harmless virus is used to transport the missing gene into liver cells, so that the liver cells will start producing the deficient enzyme to correct the defect in body chemistry.
- Methylmalonic acidemia. (2021, August 15). Wikipedia. https://en.wikipedia.org/wiki/Methylmalonic_acidemia
- Methylmalonic acidemia: MedlinePlus Genetics. (n.d.). Medlineplus.gov. https://medlineplus.gov/genetics/condition/methylmalonic-acidemia/
- Methylmalonic acidemia | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. (2016). Nih.gov. https://rarediseases.info.nih.gov/diseases/7033/methylmalonic-acidemia
- Clark, P. A., & Myers, A. T. (2017, August 11). To Treat or Not To Treat: The Case of Methylmalonic Acidemia. Www.heraldopenaccess.us. https://www.heraldopenaccess.us/openaccess/to-treat-or-not-to-treat-the-case-of-methylmalonic-acidemia
- MMA (methylmalonic acidemia) – newbornscreening.info. (n.d.). Retrieved September 6, 2021, from https://www.newbornscreening.info/mma-methylmalonic-acidemia/
- Philadelphia, T. C. H. of. (2014, March 30). Methylmalonic Acidemia: Gavin’s Story. Www.chop.edu. https://www.chop.edu/stories/methylmalonic-acidemia-gavin-s-story
- About Methylmalonic Acidemia. (n.d.). Genome.gov. https://www.genome.gov/Genetic-Disorders/MMA-Study-General-Information
- Jiang, Y.-Z., & Sun, L.-Y. (2019). The Value of Liver Transplantation for Methylmalonic Acidemia. Frontiers in Pediatrics, https://doi.org/10.3389/fped.2019.00087
- Echegaray, C. (2021, June 3). Patient of Monroe Carell Jr. Children’s Hospital at Vanderbilt first in world to receive new investigational gene editing therapy. Vanderbilt University. https://news.vumc.org/2021/06/03/patient-of-monroe-carell-jr-childrens-hospital-at-vanderbilt-first-in-world-to-receive-new-investigational-gene-editing-therapy/
A defining feature for people with autism is feeding-related problems, as identified by Dr. Leo Kanner in the in 1940s.
It is estimated that 70% of children with autism have feeding and / or eating problems, 36% of these problems were classified “severe” from the point of review of diagnostic records. (Romero 2016)
Caregivers and researchers have long reported that feeding children with autism is often challenging. (Kanner 1943)
Feeding disorder is a term that describes problems with eating enough or eating the right type of food. Children with autism often eat only a few types of foods—choosing certain textures or colors of food for instance, and / or indulging in disruptive meal-time behaviour. The causes of the issues are many, including sensory aversions, anxiety (e.g. after an incidence of choking, gagging or vomiting) and rigidity (aversion to change). Difficulty in chewing and swallowing the food may also be related to motor issues in children with autism. Digestion problems such as slow stomach emptying may also be a cause.
Eating disorders could also refer to anorexia or bulimia, caused fear of weight gain. Researchers suggest an overlap between anorexia and autism in some young women. (Wentz 2005)
Chronic overeating is another common problem among both children and adults on the autism spectrum. This could also be a result of poor sensitivity to internal cues such as feeling full. The aversion to strong flavours, textures and smell can lead to excess consumption of high calorie, low nutrient foods.
In addition, increased appetite is a common and serious side effect of the only FDA-approved medicines for autism-associated challenging behavior (agitation) – risperidone (Risperdal) and aripiprazole (Abilify). (Maayan 2011, Scahill 2016) The result is a high incidence of obesity – often combined with nutritional deficiencies – in both children and adults on the autism spectrum. (Shmaya 2015, Croen 2015, Hill 2015)
Another feeding disorder associated with autism is eating non-food items such as sharp objects like nails, broken glass and pins as well as poisonous substances such as paint chips, swimming pool chlorine tablets. This disorder, called PICA, appears among those whose autism is complicated by intellectual disability, and can cause tremendous stress on caregivers as they demand constant vigilance.
Restricted / picky eating
Studies find that 75% of children with autism are highly selective “picky” eaters. (Emond 2010, Beighley 2013, Castro 2016) Studies also suggest that these children are more likely to be underweight and have one or more nutrient deficiencies. (Zimmer 2012, Mari- Bauset 2015) Care givers /parents need to approach health care professionals who can assess the child’s diet and nutrition and help them with a customized therapy plan.
Overeating and obesity
Unhealthy weight gain starts surprisingly early in life for children affected by autism. (Oregon Health & science university, 2015) Investigators found that chances of being overweight or obese increased with the number of psychoactive behavioural medicines a child or teen was taking. (Hill 2015) Weight gain related to behavioural medication is a major concern for specialists in autism health care. (Coury 2014) Dietary approaches such as healthier food choices, monitoring portion size and increasing daily exercise is the first line solution. High calorie foods can be removed from refrigerators and pantries. Encouraging family activities such as walking or riding bicycles can help in weight management and has the added advantage of reducing a child’s behavioural problems.
Autism-friendly communication tools and daily schedules while increasing nutrition and exercise help curb overeating, says behavioural therapists. (Ward 2015) People with autism (children, teens or adults) engage less in physical activity when compared with typically developing children. (Rimmer 2007, Rimmer 2008) Social difficulties result in reduced involvement in team and competitive sports. They prefer more solitary physical activity such as running, bicycling and swimming. (Potvin 2013) It is found that physical activity has the strongest influence among children with special needs. (Yazdani 2013)
Some people with autism may also find difficulties because of food restrictions and increased activity levels. When behavioural strategies fail, parents find it difficult to choose a child’s physical health and a behavioural medicine that helps them in improving their child’s ability to function on a daily basis. Long term health consequences like obesity need to be addressed with more research.
Recognizing and treating PICA
PICA can prove deadly as it may result in choking, poisoning, infection or gastrointestinal perforation. (Decker 1993, Williams 2012) Pica-related problems include broken teeth or other dental problems, constipation, bowel obstruction and chronic lead poisoning. Researchers suggest that PICA can be decreased with behavioural therapy, if they can identify possible medical causes which need to be ruled out by a physician. (Call 2015). Medical causes can include nutritional deficiencies in iron or zinc and/or infection with intestinal parasites. Generally, people with pica also need evaluation for possible lead poisoning.
Sri Lakshmi H A (Senior Nutritionist)
ADHD, schizophrenia, bipolar disorders and autism are neurodevelopmental conditions that appear to have roots in early brain development. (Munesue 2008, Sikora 2012, Rapoport 2012) Anxiety and depression may stem, at least in part, among people with autism-related impairment that increases daily stress and social isolation, and decreases overall quality of life. (Vasa 2016, Greenlee 2016)
Epidemiological studies suggest that between 54 and 70 percent of people with autism also have one or more other mental health conditions. (Simonoff 2008, Hofvander 2009, Croen 2015, Romero 2016)
For people with autism, untreated mental health conditions can profoundly worsen behaviour. The challenging part is the overlapping symptoms, which is more difficult to identify in people with autism. (Levy 2010, Sikora 2012, Miodovnik 2015) Social withdrawal associated with depression or schizophrenia, for example can be difficult to distinguish from autism-related social impairment. Expressing the emotions and other internal feelings makes it more difficult to identify in people with autism.
In order of estimated prevalence:
- Attention deficit and hyperactivity disorder (ADHD) affects an estimated 30 to 61 percent of people with autism. (Goldstein 2004, Lee 2006, Gadow 2006, Romero 2016)
- Anxiety disorders affect an estimated 11 to 42 percent of people with autism. (Vasa 2016, White 2009, Croen 2015, Romero 2016)
- Depression affects an estimated 7 percent of children and 26 percent of adults with autism. (Greenlee 2016, Croen 2015)
- Schizophrenia affects an estimated 4 to 35 percent of adults with autism. (Chisolm 2015)
- Bipolar disorder affects between 6 and 27 percent of people with autism. (Munesue 2008, Rosenberg 2011, Vannucchi 2014, Guinchat 2015, Croen 2015)
Autism and Attention Deficit and Hyperactivity Disorder (ADHD)
The Centers for Disease Control and Prevention (CDC) estimates that ADHD affects 6-7% of the general population (Perou 2013). Studies from the last decade suggest that between 30-60% of people with autism also have symptoms of ADHD. (Goldstein 2004, Lee 2006, Gadow 2006, Romero 2016)
Geneticists have found that many of the gene variations that increase autism risk also the increase risk for ADHD. (Lionel 2011)
Hyperactivity, inattention and / or impulsivity that interferes with daily life, social development and learning are few persistent patterns of symptoms of ADHD. Close attention to detail and careless mistakes at school or work often occur among people with ADHD. Inattention is often observed, they don’t appear to listen when spoken to or have trouble organizing tasks and do not follow through with the instructions and assignments, especially those which require sustained attention. (DSM- 5 2013)
More than 3,000 patients, aged between 2-18 were observed deeply for autism and ADHD symptoms in Autism Speaks Autism Treatment Network. (Sikora 2012) Multiple symptoms of ADHD were found in more than half these children and teens with autism. Further evaluation showed that a combination of ADHD and autism symptoms resulted in significantly worse health, daily function and overall quality of life.
In 2013, the American Psychiatric Association specified that a person could be diagnosed with either autism or ADHD, but not both. (DSM-IV 2004) Later in 2013, the association changed its guidelines to allow diagnosis of both conditions in one person. (DSM-5 2013). Diagnosis of either one of these disorders tends to significantly delay the treatment of the other. (Miodovnik 2015) Impaired social development and difficulties with attention, learning and communication remains challenging to distinguish among people with autism and ADHD.
The journal Pediatrics published the first guidelines on the evaluation of ADHD among children and teens with autism, together with guidance on selecting and evaluating the best ADHD medication for those patients. (Mahajan 2012) It includes evaluating the benefits and side effects of ADHD medication depending on their dosages, in consultation with the family. The emphasis here is on the highly personal nature of such medication, and the necessity of involving the individual and / or parents in evaluating goals and needs.
Autism and anxiety
One or more anxiety disorders is seen in 11-42% people with autism, as per the studies. (Vasa 2016, White 2009, Croen 2015, Romero 2016) By contrast, CDC estimates that anxiety disorders affect 3% of children and 15% of adults in the general population. (Perou 2013, Kessler 2009) Disorders include separation anxiety, panic disorders and phobias (extreme fear of certain noises, places and so on).
For many children with autism, anxiety increases in adolescence. Social anxiety or extreme fear of meeting new people, crowds and social gatherings/ situations is especially seen amongst people with autism. (Bellini 2006) Case studies suggest that anxiety remains high throughout life. (Gillott 2007, Moss 2015)
It is also seen that though symptoms of anxiety disorders may be absent in many people with autism, they have difficulty in controlling anxiety once something triggers it. Anxiety is wrapped around autistic behaviour such as difficulty in navigating social situations and extreme sensory sensitivity to loud noises, lights, certain tastes and smells. “Anticipatory anxiety”, produced when simply anticipating or otherwise thinking about an anxiety, can also trigger extreme anxiety. Another reason or source of anxiety involves the need for routine or sameness. Lack thereof can produce anxiety in the face of changes in schedule or familiar people – for example a new teacher aide or even store clerk.
Research on anxiety in autism has been focused on children and adults who are verbal and have normal to high intelligence. Experts agree that there is need for more studies among people with autism who are non-verbal or minimally verbal and / or have intellectual disability.
Identifying and treating anxiety
It is known that people with autism have trouble assessing and expressing how they feel. Their behaviour often provides the best clues to underlying anxiety. The impact of anxiety can trigger strong internal sensations of tension that include a racing heart, muscle tightness and stomachache. These strong feelings can prompt an increase in self soothing, repetitive behaviour (flapping, rocking, spinning, etc.) and / or destructive or self-harming behaviour (shredding clothing, head banging etc). Anxiety can be cause of new resistance to what had been an enjoyed activity (a trip, a birthday party, school, etc.).
The first guidelines were published in 2016, in the journal Paediatrics. The treatment must be personalized depending on the level of the patient, which may also include language level and intellectual ability, which influences cognitive behaviour therapy. (Wood 2009, Drahota 2011, Wood 2015)
Cognitive behavioural techniques include challenging negative thoughts with logic, role playing, modelling courageous behaviour and gradual exposure to feared situations. Gradual exposure can start with looking at a related picture. This approach includes the use of visual aids, which have a strong impact on people with autism. The therapist may use a favourite cartoon character to model coping skills. It is also seen that people with autism respond strongly to the logic in cognitive behavioural therapy. This therapy has proven effective, especially among those who are verbal and have normal to high intelligence. (Wood 2009, Wood 2015, Hepburn 2016) Researchers are working on modifying the approach for those with intellectual disability with little or no verbal language. (Danial 2013)
Autism and depression
It is estimated that 7% of children and 26% of adults are affected with depression. (Greenlee 2016, Croen 2015) The journal of Pediatrics found that depression rose dramatically with age from just under 5% in a grade schooler to just over 20% in teenagers. (Greenlee 2016) Likewise with intellectual ability (IQ) – the presence of one or more medical conditions accompany autism, particularly seizures and gastrointestinal issues. Depression has a profound effect on overall quality of life which rise with age and medical conditions. Screening for depression as a routine part of care for people with autism particularly those with normal to high IQ and also with those who have additional medical issues.
Chronic feelings include, sadness, hopelessness, worthlessness, emptiness and / or irritability. Social isolation, moving or talking slowly, feeling restless and having trouble sitting still or concentrating are a few other common things identified in depression. Thoughts about death and / or suicide is at most serious in depression.
As it is well known, identifying depression is a challenge among people with autism. (Gotham 2015) Having a “flat” or unemotional, facial expression for example, is a common trait of both autism and depression. So too is irritability and social isolation. Difficulty in identifying and expressing how they feel, is the most challenging part for people with autism. Specialists have been developing and testing revised methods for identifying depression among people in the autism spectrum. (Streling 2015)
Cognitive-behavioral therapy has shown promise for treating depression in people with autism. (Kuroda 2013) This work builds on a much larger body of research using an autism-modified version of cognitive behavioral therapy for extreme and chronic anxiety. There are no FDA-approved medications specifically for depression in patients who have autism, so psychiatrists typically prescribe those used for the general population. More research may be warranted given a 2011 study suggesting that patients with autism are more likely to experience antidepressant side effects. (Boyd 2011) The most common of these include sleepiness, agitation, increased irritability, restless leg syndrome and gastrointestinal problems.
Autism and schizophrenia
In the 1960s, psychiatrists referred to autism as a subtype of childhood schizophrenia. (DSM II 1968) A clear distinction between the two conditions was made in the year 1990. (Rapoport 2009) Interestingly they share many biological similarities. Both appearing to have roots in prenatal brain development. They share similar prenatal risk factors including maternal inflammation and infection as well as advanced parental age at the time of conception. (Patterson 2009, Menon 2011, Insel 2010) Research has also identified many common genetic risk factors. In other words, many of the same gene changes are known to increase autism risk also increase the risk of schizophrenia. (Guilmatre 2009, McCarthy 2014)
Autism and schizophrenia both involve impairments in processing language and understanding other people’s thoughts and feelings. Clear differences include the schizophrenia’s hallmark psychosis, which often involves hallucinations. Autism core symptoms emerge between 1-3 years, schizophrenia is in early adulthood.
The studies found schizophrenia in 4-35 % of adults who have autism and found autism in 4-60% of those who have schizophrenia. By contrast, schizophrenia affects an estimated 1.1 percent of the general population, and autism affects an estimated 1.5 percent. (NIMH/Regier 1993, Baio 2014)
Autism and bipolar disorder
Bipolar disorder is a mood disorder once known as “manic depression.” People with bipolar disorder tend to alternate between a frenzied state known as mania and episodes of depression. While some people experience only the manic episodes, most alternate between these two states and can show extreme irritability.
People with autism are at increased risk of bipolar disorder as per the researchers. (Munesue 2008, Rosenberg 2011, Vannucchi 2014, Guinchat 2015) Prevalence of bipolar disorder ranges from 6-27% among people with autism. Bipolar disorder affects 4% of the general population (Kessler 1994)
Some leading experts propose that bipolar disorder may be over-diagnosed in those who have autism, due to overlapping symptoms such as hyperactivity, irritability and disturbed sleep. (Witwer 2014) For example, a child with autism may be consistently high-energy and socially intrusive through childhood. As such, her tendency to talk to strangers and make inappropriate comments are likely a consistent part of her autism, not symptoms of a manic mood swing.
Treatment of bipolar disorder in autism
Some bipolar disorder medications can be problematic and even dangerous in someone who has difficulty recognizing and expressing feelings – as is common with autism. Lithium, for example, can in rare cases produce life-threatening toxicity. Anti-seizure, mood-stabilizing medication such as valproic acid may be a safer treatment for those with autism. (Witwer 2014) In addition, the antipsychotics risperidone and aripiprazole are both FDA-approved to treat irritability in children with autism, though both tend to produce significant weight gain and diabetes risk.
Sri Lakshmi H A (Senior Nutritionist)
People with autism may also suffer from disrupted sleep. Studies have found that more than 50% of the children with autism and possibly as many as four in five have one or more chronic sleep problems. (Cortesi 2010, Krakowiak 2008) Few commonly faced problems include difficulty falling asleep, prolonged wakening during the night and extremely early raising.
Sleep issues may have an effect during the day on the behavioural challenges for children with autism, which includes spikes in repetitive behaviour, difficulty in communication, hyperactivity, irritability, aggression and inattention – which have a huge impact on learning and a decrease in the overall quality of life. (Mazurek 2016)
It is well known that people with autism may have sleep issues and that goes hand in hand with day time behavioural challenges which might interfere in their learning and negative impact on the overall quality of life.
It was reported from many parents who are unable to sleep themselves for fear that their children will leave their rooms or even their homes in the night. Wandering from safety, or elopement is a common and life-threatening problem affecting nearly 50% of the children with autism above 4 years. (Anderson 2012) In 2006 a study found “significant” levels of chronic stress in 90% of parents of “problem sleepers” with autism compared to 65% of parents of non-problem sleepers with autism. (D00 2006)
Studies have shown that genes play an important role in regulating the body’s sleep-wake cycle (circadian rhythm), people with autism are twice as likely to have mutations in genes that regulate the circadian rhythm.
What causes autism-related sleep problems?
Research suggests that the cause of disrupted sleep in people with autism goes beyond poor sleep hygiene habits that disrupt sleep in the general population (Johnson 2008). Many potentially biological causes are identified from various studies, which likely vary and sometime overlap – in different people.
- Genetic studies have shown that people with autism are twice as likely as other people to have mutations in genes that regulate the body’s sleep-wake cycle (circadian rhythm). (Yang 2015)
- Seizures and sleep can worsen each other – undetected seizures during the night disrupts sleep patterns and lack of sleep or insufficient sleep worsens seizure control in people with autism who also have epilepsy. (Accardo 2015)
- Anxiety can affect sleep. It can interfere with the ability to fall asleep and stay asleep. Studies suggest that 11- 40% of children and teens with autism struggle with one or more anxiety disorders. (Vasa 2016, White 2009) It can also set up a worsening cycle with insufficient sleep worsening anxiety and depression.
- Rapid eye movement (REM) is associated with dreaming, and plays an important role in learning, memory and brain development. Studies suggest that children with autism spend relatively less time in REM stage of sleep than do other children. Children with autism spent around 15% of their sleep time in REM versus 23% of the other children. (Buckley 2010). The importance of REM has created a new interest for scientists to look more broadly at autism-related changes in the neuro-transmitter (brain-signalling molecules) that help control sleep.
- Melatoni so called the sleep hormone, produced by the brain, is found to be produced at lower levels in people with autism. (Nir 1995, Kulman 2000, Tordjman 2005, Melke 2008) A recent study found there is little difference in melatonin levels between children with and without autism. It concluded that autism-related sleep difficulties are not solely driven by biological differences. (Goldman 2017)
Fostering better sleep
Neurologist and sleep specialist Beth Malow, of Vanderbilt University Medical Center, has pioneered research-based clinical guidelines for evaluating and addressing sleep disturbances in children with autism, (Malow 2012) as well as programs designed to teach parents strategies for improving the sleep of children with autism. (Malow 2014)
Sri Lakshmi H A (Senior Nutritionist)