A mother with a mitochondrial DNA gene mutation will pass this abnormal gene to all of her children. The children will all be affected, but with different degrees of severity.
As it is not possible to predict how the children will be affected, this is immensely difficult for planning a family.
Infantile subacute necrotizing encephalopathy.
Clinically heterogenous, lots of different genes. Can be X-linked, mitochondrial or recessive!!! Main genetic problem is mitochondrial complex defect, but same disease can be caused by pyruvate dehydrogenase defect (actually a complex of enzymes).
Baby’s initial development may appear normal, although there may be failure to thrive. Lactate can be raised in serum. Progressive, often rapid, neurological deterioration including hypotonia, dystonia, seizures.
Lesions (necrotic, gliosis, spongiosis) seen in basal ganglia, brainstem, cerebellum, spinal chord. CSF lactate and pyruvate may be raised, even if serum normal.
See mitochondrial inheritance.
It is acceptable for staff to receive small tokens of gratitude from a relative or carer in appreciation of care and treatment received. These are typically cards, chocolates or biscuits. Where staff are offered gifts of greater value these must be politely refused. [bottles of wine? Whisky?] If this is difficult they must refer the matter to their line manager.
Hospitality
It is acceptable for staff to receive small promotional items, e.g. pens, calendars, diaries. However,
Note – the term ‘gift’ includes benefits such as provision of services at a cost below that generally charged to members of the public.
Modest hospitality may be acceptable provided it is normal and reasonable in the circumstances e.g. lunches in the course of a working visit. Any hospitality accepted should be similar in scale to that which the NHS as an employer would be likely to offer.
All other offers of hospitality should be declined.
Staff should register with their line manager all such modest hospitality which they wish to accept, using the hospitality register declaration form (Appendix 3). In cases of doubt, staff should seek advice from their line manager.
If the nature of the event dictates a level of hospitality which exceeds this, then the individual should ensure that their line manager is fully aware of the circumstances and approves their attendance. An example of such an event might be an awards ceremony involving a formal dinner. If the line manager grants approval to attend, the individual should declare their attendance in the register of hospitality held by their line manager. The approving manager must ensure that this will not result in any future conflict of interest.
If the individual is invited to an event in a private capacity (e.g. as result of their qualification or membership of a professional body), they are at liberty to accept or decline the invitation without referring to their line manager. The following matters should however be considered before an invitation to an individual acting in a private capacity is accepted.
a) The individual should not do or say anything at the event that could be construed as representing the views and/or policies of NHS Lanarkshire.
b) If the body issuing the invitation has (or is likely to have, or is seeking to have) commercial or other financial dealings with NHS Lanarkshire, then it could be difficult for an individual to demonstrate that their attendance was in a private and not an official capacity. Attendance could create a perception that the individual’s independence had been compromised, especially where the scale of hospitality is lavish. Individuals should therefore exercise caution before accepting invitations from such bodies and
must inform their line manager.
c) Where suppliers of clinical products provide hospitality it should only be accepted in association with scientific meetings, clinical educational meetings or equivalent, which must be modest, normal and reasonable in the circumstances and in line with what the NHS would normally provide. Any such hospitality should be held in appropriate venues conducive to the main purpose of the event.
Sponsorship [should be] clearly disclosed in any papers relating to the meeting; products discussed should be described in relation to the Scottish Medicines Consortium, Formulary and the active promotion of clinical products is restricted to those in the Board’s Formulary and equivalent clinical product catalogues.
Any educational meetings hosted by suppliers must be approved by the line manager.
Before accepting an offer of hospitality the individual concerned should fill in a Registering Hospitality Declaration Form (attached as appendix 3) and have it approved by their line manager. A copy of the request form will be held as part of a Hospitality Register which will be available for scrutiny by the
NHS Board, Corporate Management Team, members of the public or press should they request such information.
Legumes, pulses, beans… Some terminology first: legumes are plants in family Fabaceae (or Leguminosae). Pulses are (strictly) those cultivated for DRY seed, as opposed to green beans, broad beans etc that are eaten fresh. Lentil simply describes shape (“like lens”). So other examples of legumes are peanut, lupin, tamarind, carob, alfalfa!
Very common cause of food allergy, even excluding peanut! And varies across different cultures, depending on typical pulses used. Fifth most common cause of food allergy in Spain. In India, often a trigger of asthma/rhinitis when being boiled. Cross sensitivity is seen, but not automatic, and hard to predict.
Soya allergy is sometimes seen in highly atopic babies, but otherwise actually pretty rare (except in Japan) – lucky, cause gets into lots of different things eg many breads. Soya lecithin is a common additive, used to make texture more smooth, but usually only in very small amounts. Fermentation eg soy sauce appears to significantly reduce allergenicity, soya flour also seems less allergenic than soya milk, even though most of the allergens are cupins eg 2s albumin and would therefore be considered heat stable.
Lupin is used in some continental baked goods, for example packaged waffles. A good proportion of peanut allergic children will be allergic to it too, but as lupin is not found very commonly most will never know or have a problem with it. A few restaurants (in UK and abroad) have lupin in their allergy menus.
A couple of lentil allergens have been identified including a vicilin and a lipid transfer protein. In my experience pappadoms can often be tolerated – there is certainly evidence that autoclaving for 30 mins can affect binding, but these are only deep fried for a few seconds.
Both the known pea allergens are vicilins, hence cross reactivity with lentil. Chickpea allergens however are not (one a prolamin, the other a cupin) – still, cross reactivity fairly common.
French beans have an LTP so potentially severe, and potentially fruit allergies too. Green (mung bean) and red gram are cupins, black gram appears to be something else.
[Clin Rev Allergy Immunol. 45(1):30-46, 2013 Aug]Usually develops over a few weeks, not an acute drug allergy!
Rash is maculo-papular, not specific. Apart from eosinophilia, other blood abnormalities occur eg atypical lymphocytosis or lympho/thrombocytopenia.
The systemic features are fever and lymphadenopathy, but generally 1 or more organs, typically liver, kidney and lung involvement.
Gillick ruling (1985) was primarily about sharing of information with parents (use of oral contraceptive), not about going against their decision!
You should involve children and young people as much as possible in decisions about their care, even when they are not able to make decisions on their own (GMC).
Competence is not binary, it varies according to context and over time. You need to assess ability to:
And you need to assess context:
Even then, you should encourage involvement of parents. In difficult situations, consider involving multidiscip team, independent advocate, child protection teams. ”You should not make unjustified assumptions about a child or young person’s best interests based on irrelevant or discriminatory factors, such as their behaviour, appearance or disability”.
At 16yrs, a young person can be presumed to have the capacity to consent. In Scotland, parents cannot authorize treatment a competent young person (even under 16yr) has refused. In E&W/NI, High Court can override up to 18yrs – “children and young people have a right to consent, but not to refuse treatment if this would put their health in serious jeopardy” (BMA consent toolkit). Court rulings have gone both ways.
Neuberger criteria: competence, information, understanding, voluntariness. All dubious!
GMC guidance on consent (2008) – places it in context of process of discussion and decision-making. There is no “once size fits all” method. Starts with information being provided, in different formats. References advocacy services. Does not set threshold values for discussing risks: sensible, given how complex the communication of risk can be!
Acknowledges that some patients do not wish to go into detail about their condition. While doctors must respect their patients’ wishes, there is a minimum level of information that a patient is likely to need in order to give valid consent.
Adults with Incapacity Act (Scotland 2000) and Mental Capacity Act (England 2005) establish mechanisms for incapacitated adults. Provides practical advice on assessing capacity.
In Scotland, legal age of consent is clearly defined as 16yrs (Age of Legal Capacity (Scotland) Act 1991). In England, Family Law Reform Act 1969 defines “child” as under 18yrs! This leads to some issues when it comes to competency.
Written consent – the law only requires written consent for a very few things, eg IVF, organ donation! But you must record the fact that you have gained consent in medical records. And it may just make everything easier to get it written anyway.
Proxy consent by parents can create conflict of interest eg handicapped child. Authorization a better concept (presumes right of child to take part in research)? Non-therapeutic research is not strictly legal, but usually accepted if minimal risk ie not significantly increased risk compared with standard care. Right of research enshrined in possibility of benefit outweighing possible risks. Alternative is therapeutic orphans, treated without good evidence of benefit. Failure to conduct research led to prophylactic sulphonamide disaster in 1950s (increased kernicterus). Research without consent not strictly legal but possibly acceptable for emergency situations, but retrospective consent should be sought (not really consent at all, of course) else assent (simplified consent) with later ratification, in stages if necessary.
Reasons for refusal in EURICON study: perceived risks/distress; distrust of research/researchers; dislike of the tone of approach of the doctor; shock and inability to decide; inconvenience of follow up. Hence communication skills essential. Information sheet should be given but should not be relied upon. As a minimum, parents must know that the treatment is being given as part of a trial, that their child may be receiving an experimental or unproven treatment, that they are free to say no and to opt for standard treatment. Check list should be provided. Involvement of independent committee should be highlighted. Feedback to parents should be encouraged.
Inability to give consent eg children, unconscious, learning difficulties does not mean research should not be done – indeed that would deprive patients and others of potential benefit. But should only be done if unable to do same study with patients who can give consent; risks should be minimal (for non-therapeutic research that means equivalent to everyday life or minimally invasive therapeutic interventions; assent should be sought from appropriate advocates eg relatives, who should be provided with the same information which would have been given to a competent patient; research should be explained after its completion to participants who have regained their competence subsequently (NOT retrospective consent, mind you).
Use of medical records without consent is a moral wrong – should be balanced against potential benefit. Patients should be informed of this potential use of their records and reassured about confidentiality. Only do if consent not praticable; research is of sufficient merit and has potential benefit; identifiers should be removed where possible; contact with patients is not anticipated; permission should be gained from responsible clinician.
For births registered in Scotland, a father acquires parental responsibility if he was married to the mother at the time of the child’s conception or
subsequently. An unmarried father will acquire parental responsibility if he is recorded on the child’s birth certificate and the child was born on or after 4 May 2006 (Scotland), December 2003 (England).
If not on the birth certificate, an unmarried father must obtain a court registered parental responsibility agreement or order. Birth certificates can be updated with new information.
Parental responsibility is not lost automatically with divorce, loss of custody rights, or if a parent makes no financial contribution! Young people under the age of 16 who bear children still get rights, although usually additional support will be necessary.
Foster parents usually do not have parental responsibility – that remains with the local authority and the birth parents. The parental rights of a child born under a surrogacy arrangement remain with the surrogate until the new parents complete adoption procedures or else obtain a court order (under the HFE Act).
Parents are allowed to authorize 3rd parties eg child minders, Grandparents to take over particular responsibilities. In terms of the Childrens Act, what is reasonable to safeguard/promote the child’s welfare is permitted to such carers (in loco parentis). If however the parent is thought likely to
object to a treatment decision, only emergency actions are acceptable pending contact with the parents directly. Competence of child themselves obviously relevant too.
Up to 6 people can have PRRs for the same child. But becomes unmanageable!
Decisions regarding the following should involve consultation between all with PRRs:
But PRRs are not a weapon for interfering with day to day life! Gillick ruling made it clear that parental rights exist only for the benefit of the child! Less serious decisions may simply require other party to be informed.
Stepfathers are in a funny position. Marrying the mother gives rights, but does not remove rights from biological father. Not being married leaves only the option of adoption, or else applying for court order if later separation after being an important part of a child’s life.
Non-consensual adoption under close judicial scrutiny – the consent of the parent with capacity can only be dispensed with if “nothing else will do”, and not because providing requisite support is difficult.[https://ukhumanrightsblog.com/2013/10/01/when-adoption-without-consent-breaches-human-rights/]
Civil Partners – biological parents remain the legal parents. Civil partnership confers equivalent step-parent status as married non-biological parent. Parental responsibility can therefore be obtained either by consent of biological parents, court order or adoption.
Residence Order confers PRRs too. Contact Order does not.
It should be noted that parents who do not have parental responsibility may also play an essential role in determining best interests and may have a right, under the Human Rights Act (rights, as individuals, to respect for private and family life – Article 8), to participate in treatment decisions [BMA toolkit].
Thyroid issues can be congenital, neonatal, autoimmune, or related to syndromes eg Downs, Digeorge.
Note that thyroid function tests can be affected by intercurrent illness, there is also viral thyroiditis where you might get transient (usually mild) abnormalities. So borderline results (especially if asymptomatic or other medical issues) usually just need repeated. If results confusing, do T3. If normal then abnormal T4 likely to be transient. If suspicion of evolving problem, do autoantibodies (TPO antibody, Thyroid Receptor Ab (TRab)). If progressive decline then likely to be emerging autoimmune condition.
All kinds of unusual clinical presentations in thyroid disease, for example:
Isolated TSH elevation >20 is usually treated.
True congenital hypothyroidism mostly dysgenesis, ie poorly formed gland, of which <2% have identified mutations (mostly thyroid peroxidise, thyroglobulin and TSH receptor proteins – EDTA sample, Dr Therese Bradley at SGH Genetics). May be due to dyshormonogenesis (10%, autosomal dominant, gland looks normal on scan), TSH Receptor defect. Do a Family History.
Mostly found on newborn screening now. Life long.
Placental thyroxine important, iodine too, on neonatal thyroid function. In the first 14/7 of life, high TSH/T4/T3 seen. Transient neonatal hypothyroidism seen, 25% of +ve guthrie tests!
If missed or untreated, classic signs are umbilical hernia, goitre, hoarse cry, coarse facies, Developmental Dysplasia of Hip!
SPEG recommend that all families should be given the opportunity for imaging, subject to availability, because more informative than blood tests alone, will aid in genetic counselling, likelihood of lifelong treatment if proven permanent CH, provides a useful guide as to thyroxine dose.
Combined isotope and ultrasound imaging (dual scanning) is preferred. Isotope scans should be performed by day 5 of start of treatment to ensure avoidance of false negatives due to TSH suppression (advisable to take thyroid function sample on day of scans to confirm reliability of results). Ultrasound may show an abnormal gland (dyshormonogenesis) or else agenesis (no gland). But in agenesis may be remnants of embryonic structural elements which can be mistaken for a gland – can persist into teenage years but max 5mm x 5mm! Hence importance of supporting radio-isotope imaging. Experience of ultrasonographer important.
Some concern that thyroxine liquid not as consistent levels? Automatic script request from pharmacy, patient then notified when ready.
Repeat TGTs at 10-12 weeks. Aim to keep TSH in lower half of reference range (room to spare as child grows).
Aim for fT4 > 15 pmol/l and TSH <5.0 mU/l
| Age | LT4 dose (ug daily) | LT4 dose (ug/kg/day) | ||
| Female | Male | Female | Male | |
| 3 months | 41.3 | 43.3 | 7.2 | 6.9 |
| 6 months | 45.8 | 50.0 | 6.1 | 6.2 |
| 9 months | 47.9 | 53.1 | 5.6 | 5.7 |
| 12 months | 55.0 | 53.1 | 5.8 | 5.2 |
| 18 months | 62.5 | 61.1 | 5.8 | 5.3 |
| 24 months | 70.3 | 58.3 | 5.9 | 4.6 |
| 36 months | 75.0 | 62.5 | 5.3 | 4.25 |