Discussing psychometabolism: meaning the relation between child psychopathology and inborn error of metabolism – PowerPoint PPT presentation

3. UNDERESTIMATED
PSYCHOMETABOLIC ASPECTS IN
CHILD PSYCHIATRY
BY:
SAMIR M MONIR
LECTURER OF NEUROPEDIATRICS
MINIA UNIVERSITY

4. (METABOLISM AND PSYCHE)
Still offering an amazing area in research

5. “Inherited” and “metabolic diseases” two words send chills down the
spine of a junior doctor and represent endless hours one spent learning
all about mutations, enzymes, co‐enzymes and substrate deficiencies and
still failed to grasp the complexity of the problem.
Dr: Clarke. 2006; Cambridge University

6. BRAIN
• 1.36 kg
• Over 100 billion neurons, or signaling
units.
• Controls everything we do
• If injured, it may affect basic functions,
including thought, behavior, memory
and speech
• Underappreciated organ

7. • Metabolism (from Greek, metabolē, "change") can refer to all
chemical reactions that occur in living organisms.
• Metabolism is usually divided into : Catabolism, that breaks down
organic matter and produces energy by way of cellular respiration and
anabolism that uses energy.

9. METABOLIC PATHWAYS

10. We will discuss:
Historical Background
Psychiatric Presentation of Metabolic Disorders
Metabolic Disorders and Common Neurodevelopmental Syndromes
Diet , Nutritional Disorders and Child Psychiatry
Psychopharmacologicl Aspects
Family Aspects
Acknowledgement

11. Historical Background:
Inherited disorders have accompanied humanity since its
earliest existence as remarkable in many prehistoric and
historic sites. In Egypt, investigation of mummies from the
huge necropolis of Thebes-West in Upper Egypt revealed
osseous manifestations suggestive of metabolic disorders.

12. Pharaoh Akhenaten, might had the
aromatase excess syndrome.

13. The periodic “madness” of King George III has been
attributed to acute intermittent porphyria (AIP)

14. Van Gogh.

15. Metabolic disorders caused by genetic mutations resulting in
enzyme deficiencies in an intermediary metabolic pathway,
constitute a wide spectrum of diseases in clinical practice.
The term ‘inborn errors of metabolism’ was introduced by
Sir Archibald Garrod at the beginning of the twentieth
century.

17. More than 6500 inherited disorders, known to affect world populations. The
overall incidence was estimated to be 1 in 1,400 live births. However, this rate
may be an underestimation, as new disorders continue to be discovered
because improvement in diagnostic techniques sensitivity and accuracy.
Although individually rare, they are collectively numerous. Prevention of
death or permanent neurological sequele is dependent on early diagnosis and
initiation of appropriate therapy . Diagnosis is done by clinical assessment,
imaging studies, electrophysiological, histopathological and biochemical
studies).

18. Raghuveer et al; 2006

19. Psychiatric Presentation of Inborn Errors of Metabolism
• Neurological dysfunction is an important manifestation of inherited
metabolic disorders.
• Over one-third of the inherited metabolic disorders are characterized
by the central nervous system involvement. Neurological symptoms
are the presenting and the most prominent clinical problems
associated with them. Among the neurometabolic disorders, there are
particularly five common neurological presentations: chronic
encephalopathy, acute encephalopathy, movement disorder, myopathy
and psychiatric or behavioral abnormalities

20. Child psychiatry, in particular, needs miracles to unravel all its mysteries.
Inborn errors of metabolism (IEMs) may present in childhood,
adolescence as well as adulthood as a phenocopy of a psychiatric
disorder. Fortunately, many of these IEMs are treatable. However,
diagnostic procedures and specific therapeutic modalities should be early
at the 'psychiatric stage' to be effective. After that the occurrence of
irreversible neurological lesions or profound mental delay will appear.

21. It is important to detect metabolic disorders for several reasons:
• (1) Specific treatments may be available
• (2) Metabolic decompensation may be avoided
• (3) Accurate counselling may be given.
• Sedel et al did a schematic classification of metabolic disorders into three
groups according to the type of psychiatric signs at onset.
• Group 1 represents emergencies, in which disorders can present with acute and recurrent
attacks of confusion, sometimes misdiagnosed as acute psychosis. Diseases in this group
include urea cycle defects, homocysteine remethylation defects and porphyrias.
• Group 2 includes diseases with chronic psychiatric symptoms arising in adolescence or
adulthood. Catatonia, visual hallucinations, and aggravation with treatments are often
observed. This group includes homocystinurias, Wilson disease, adrenoleukodystrophy and
some lysosomal disorders.
• Group 3 is characterized by mild mental retardation and late-onset behavioural or
personality changes. This includes homocystinurias, cerebrotendinous xanthomatosis,
nonketotic hyperglycinaemia, monoamine oxidaseA deficiency, succinic semialdehyde
dehydrogenase deficiency, creatine transporter deficiency, and a and b mannosidosis.

23. • The need to screen for an inborn error of metabolism
arises out of the fact that most cases take to irreversible effects as
time progress. Emphasis has to be laid on early detection and prompt
management,

24. Algorithm for patients with a number of treatable
inherited metabolic conditions.

25. organic causes of psychosis should be considered among patients with atypical
psychiatric symptoms After further diagnostic processes, easy-to-apply screening
tests are now available that can assist in confirming diagnoses

26. • Treatment used in psychiatry and which may aggravate metabolic diseases

27. Psychiatric features of inherited metabolic disorders by Turnacioglu et al., 2013

28. Psychosis

29. Psychosis
• Certain inborn errors of metabolism as homocysteine metabolism disorders,
urea cycle disorders, porphyria, Wilson disease, cerebrotendinous
xanthomatosis and Niemann-Pick disease type C can present as psychosis. It
should be considered in patients with atypical psychiatric symptoms. Some
IEMs are treatable especially during the early stages of disease (sometimes
simply with vitamin replacement or supplementation) and new treatments
continue to appear.
• Atypical psychiatric symptoms including: acute onset and /or early onset,
fluctuating course, confusion, catatonia, visual hallucinations, progressive cognitive
decline, intellectual disability, treatment resistance Unusual or severe side effects

30. Spectrum of Childhood Behavioral and Neurodevel;opmental Disorders by: Greenspan et al.,
1998
Inborn Errors of Metabolism and Common
Neurodevelopmental Syndromes

31. • Although each disorder is distinct, some clinicians do not see these
conditions as discrete entities, but a continuum of disorders with related
features. All share similar etiologies, common presentations as well as
responsiveness to common treatment approaches.
• All share common triggers: nutrient deficiencies; fatty acid abnormalities;
hyper-sensitivities or intolerances to food; adverse responses to food
additives, preservatives, artificial colors and flavorings, sulfites, salicylates
and phenols; all as co-existing problems in many of these disorders.
• Researchers suggest that incomplete digestion of wheat and other gluten
containing grains as well as milk/dairy products can be linked to behavioral
symptoms recognized in those with developmental problems

32. AUTISM

33. Autism
• Autism spectrum disorder (ASD) is the broad term includes autistic disorder,
Asperger syndrome, and pervasive developmental disorder, not otherwise
specified. These disorders share common features of impaired social
relationships, impaired communication and language, and stereotypic
mannerisms or a narrow range of interests, associated with behavioral
problems, such as hyperactivity and aggression. Although it's exact cause is
not known, several factors have been implicated in its etiology, including
inborn errors of metabolism. Although relatively uncommon, it's more likely
to occur in certain countries, such as in the Middle East, where recessive
conditions are common because of consanguinity.
• The following disorders were identified: phenylketonuria, glucose-6-
phosphatase deficiency, propionic acidemia, adenosine deaminase deficiency,
mitochondrial disorders, and branched chain ketoacid dehydrogenase kinase
deficiency.

34. ADHD

35. ADHD
ADHD occurs in approximately 4–6% of the population and is defined by
developmentally inappropriate levels of inattention, hyperactivity, or
impulsivity. A highly heritable condition thought to have its basis. ADHD is
currently categorized into three subtypes with varying rates of prevalence:
ADHD-inattentive subtype, ADHD-hyperactive/impulsive subtype, and ADHD-
combined subtype. Stimulant medications in conjunction with psychosocial
treatments such as behavioral management training for parents, are the most
efficacious treatments for ADHD

36. Developmental Delay

37. Developmental Delay
Intellectual disability (developmental delay) affects 2.5% of population
worldwide. It is a life-long and debilitating condition with deficits in cognitive
functioning (IQ less than 70) and adaptive skills, often associated with
behavioural problems (autism, hyperactivity and aggression), epilepsy and other
neurological disabilities, all resulting in psychological, social and economic
burdens. In children less than 5years of age with deficits in two or more
developmental domains (e.g. fine/gross motor skills, speech, interaction, etc.).
The etiology of ID is diverse, including infectious, traumatic and toxic causes.
Genetic etiologies constitute the most frequent cause and are demonstrable in
more than 50% of individuals with ID

40. Overview of all causal therapies (n=91).
Van Karnebeek and Stockler (2012)

42. Diet
• There's another face of food we don’t know enough, called behavior. Nutrition plays
a direct role in cognition and behavior in children and adolescents.
• Dietary treatment of children with behavioral disorders has had a controversy since
the 1920’s.
• Dietary management of IEM include: medical foods that provide the majority of
nutrient needs, specialized for individual disorders; and dietary supplements that are
used to enhance diminished catalytic function, replace conditionally essential
nutrients, or provide essential nutrients that may be missing due to dietary
restrictions.
• Common Dietary Interventions: Additive-free diet, sugar elimination diet, food
allergies, fatty acid supplementation and gluten-free, casein-free diet.

43. Obesity
Worldwide estimates of childhood obesity are as high as 43 million and it
continues to increase each year. It has been accompanied by much serious and
severe comorbidity. The psychiatric aspects related to obesity in pediatric age
are still poorly studied and the link between obesity and psychiatric symptoms
appears to be unclarified.
Many propose behavioral problems are a result of the stigmatization associated
with childhood obesity, but there is also evidence supporting that behavioral
problems may precede in some children.

45. Malnutrition
• Early childhood malnutrition is associated with cognitive and behavioral
impairment during childhood and adolescence. Malnutrition limited to the
first year of life with good health and nutrition documented to 12 years of
age, is associated with a significant overrepresentation of adult personality
trait scores outside of the average range involving: anxiety, depression,
lowered interpersonal orientation, apathy and lowered sense of self-efficacy
or competence.
• Even in mild malnutrition, subtle changes in diet may modulate brain
function. Both vitamins and minerals are essential (esp, vitamin C, folic
acid, vitamin B6, magnesium, calcium, zinc, niacin, niacinamide, and
dimethylglycine) which play a valuable role in the treatment of children with
attention deficit disorder or autism spectrum disorder.

46. Psychopharmacologicl Aspects

47. Antipsychotics and Metabolism
• There is a growing evidence supporting the presence of metabolic, neurological and
sexual/reproductive adverse effects in children treated with antipsychotics, mood
stabilizers and selective serotonin reuptake inhibitors (SSRIs).
• Adverse effects include: weight gain, obesity, glucose dysregulation, dyslipidaemia,
hyperprolactinaemia and incident cardiovascular events as orthostatic hypotension.
These side effects could lead to serious complications in children.
• This was more significant with younger ages, females, multiple drug use and with
atypical antipsychotics than typical antipsychotics.
• Special considerations should be given before initiating treatment and clinical
monitoring is essential. More research is needed to develop strategies to minimize
antipsychotic-related adverse effects and to discover treatments with lower risk
potential.

49. Family
• Little is known about parents' perspectives on child development and social impact on
families. Living with a metabolic disorder may cause considerable stress on patients and
families (Gramer et al., 2014)
• Parents of children diagnosed with ADHD were more likely to divorce and had a shorter
latency to divorce than parents of children without ADHD.
• Mothers of children with mental disorders have poor quality of life, poor sleep and high
prevalence of mental disorders; hence child psychiatry clinics need to ensure that
mothers receive appropriate care along with the child.