Vitamin Deficiency States

Aathi Pathmanathan Nov 5, 2013

Vitamin Deficiency States

Vit B12
Folate Vitamin B3 (Niacin) Vitamin E Vitamin A

Vitamin B12 (Cobalamin)

Food sources: fish, poultry, meat, fortified cereals

RDA:

Adults: 2.4 micrograms/day Pregnant women: 2.6 micrograms/day

Breastfeeding women: 2.8 micrograms/day

Vitamin B12
Functions:
RBC production

Coenzyme for fatty acid and carbohydrate metabolism and protein synthesis

Vitamin B12 Deficiency

Causes:

Dietary (eg. Vegans, EtOH)

Nitrous oxide anesthesia

Malabsorption:

Stomach: pernicious anemia, post-gastrectomy, atrophic gastritis Terminal Ileum: ileal resection, Crohn's, Celiac's

Vitamin B12 Deficiency

Megaloblastic macrocytic anemia: skin pallor, weakness, fatigue, syncope, dyspnea, and palpitations Glossitis, Angular cheilosis GI symptoms : N/V, anorexia, abdominal pain/bloating Neurological: Subacute combined degeneration of the cord Ischemic Heart Disease/Stroke risk?: Homocysteine
B12 vitamin supplementation has no significant effect on stroke risk (Huang et al , 2012)

Neuropsychiatric: Irritability, depression, psychosis, dementia

Vitamin B12 and Homocysteine Metabolism

Subacute Combined Degeneration of the Cord (Lichtheim's Disease)

Onset is insidious
Initial swelling and irregularity of myelin sheath, followed by demyeliation (reversible) and loss of axons (ireversible)

Symmetrical posterior column loss sensory and LMN signs

Symmetrical corticospinal tract loss motor weakness and UMN signs (hyperreflexia, Babinski positive, spasticity) Joint position and vibration sense affected first Pain and temperature usually preserved Also: paresthesias, areflexia, autonomic dysfunction, gait disturbance, intellectual or behavioral impairment, and impaired visual acuity

SACDC

Vit B12 Deficiency

Neurological:

Isolated numbness or paresthesias (33%) Gait abnormalities (12%) Psychiatric or cognitive symptoms (3%): Irritability, depression, psychosis, hypomania, dementia Visual symptoms in (0.5%): reduced visual acuity, usually caused by bilateral optic neuropathy and rarely, optic neuritis, cecocentral scotoma Rare: autonomic features include orthostasis, sexual dysfunction, and bowel and bladder incontinence.

Folate
Function:
Synthesis of nucleic acids

Key for the development of cells, protein metabolism; in pregnant women, helps prevent NTDs

Folate Deficiency
Causes:

Diet EtOH, poverty, elderly

Increased demand - pregnancy/lactation or Inc. turnover (hemolysis, malignancy, renal dialysis)

Malabsortion Celiac's, tropical sprue, IBD Drugs antiepileptics (Phenytoin, valproate); methotrexate, trimethoprim

*Hereditary folate malabsorption - autosomal recessive (rare)

Folate Deficiency

Macrocytic megablastic anemia: skin pallor, weakness, fatigue, syncope, dyspnea, and palpitations
Glossitis Angular cheilosis GI symptoms : N/V, anorexia, bloating

Ischemic Heart Disease/Stroke: Homocysteine

folic acid supplementation reduced the risk of stroke by 7%,but did not effect the severity or risk of death from stroke (Huo et al, 2012)

Neurological: congenital neural tube defects, cerebral folate deficiency* Depression

Neural Tube Defects

Cranial NTDs
Anencephaly Encephalocele

Spinal NTDs spina bidifa occulta meningocele myelomeningocele

Neural Tube Defects

-Historically: 1/ 1000 pregnancies - 60% to 100% reductions in NTD cases when women consumed folic acid supplements in addition to a varied diet during the periconceptional period

Etiology:
-Inadequate folate inadequate intake, or antifolate drugs (methotrexate, aminopterin) -Genetic factors high prevalence among MZ twins -Maternal diabetes -AED's- valproate, carbamazepine

Neural Tube Defects

Screening:
Ultrasound MSAFP at 15-18 wks, low sensitivity in first trimester

Neural Tube Defects

Anencephaly
-involves forebrain and variable amounts of upper brainstem
-hypothalamus typically missing; cerebellum, brainstem, optic nerves and spinal cord maybe malformed -underdevelopment/absence of pituitary adrenal hypoplasia

Myelomeningocele
-in 80% vertebral defect involves lumbar and sacral region
Neurological: Spinal cord - usually severe, causing complete paralysis or absent sensation 97% urinary or fecal incontinence Brainstem- most have brainstem dysfunction due to Chiari II malformation: dysphagia; vocal cord paresis stridor; absence of sensation Hydrocephalus (90%) due to Chiari II malformation

Cerebral Folate Deficiency

-AR disorder or autoimmune, 1/4000-6000 - decreased [ ] of 5-methyltetrahydrofolate (5-MTHF) in the CSF in the context of normal folate metabolism outside the Nervous system (active form of folate) -due to mutation on FOLR1 gene gene encodes Fr on choroid plexus epithelial cells folate transportation defect -Autoimmune: autoantibodies against Fr -Symptomatic at 4 -6 months of age

Cerebral Folate Deficiency

Clinical Features: Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal EEG: subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia: choreoathetosis, ballismus Ascending Pyramidal tract abnormalities in legs Irritability Insomnia Delayed myelination Neuroimaging: Frontotemporal atrophy

Cerebral Folate Deficiency

Late onset Cerebral Folate Deficiency:
-Juvenile onset central nervous system folate deficiency and Rheumatoid Arthritis (Koening et al, 2008)

-Adult onset cerebral folate deficiency (Sadighi Z et al, 2012)

Cerebral Folate Deficiency

Treatment: folinic acid 1-2 mg/kg/day > folic acid (may competively inhibit 5-MTHF at the Fr receptor Cow's milk free diet- human FR crossreacts with FRs in cow's milk

Vitamin E

Food sources: Fortified cereals, sunflower seeds, almonds, peanut butter, vegetable oils, avocado
RDA:

Adults (including pregnant women): 15 milligrams/day Breastfeeding women: 19

Vitamin E
Functions:
Antioxidant intercepts free radicals; prevents destruction of cell membranes Protects fat in LDL from oxidation Enhances vasodilation Inhibits platelet aggregation Inhibits activity of protein kinase C

Vitamin E

Abetalipoproteinemia
Fat malabsorption: CF, cirrhosis, cholestatic liver disease, Crohn's disease Genetic: AVED (similar to Friedrich's ataxia)

Ataxia with Vit. E Deficiency (AVED)

Rare, AR inheritance Incidence: 1 / 1 000 000

More common in Mediterranean or North African descent

Most symptomatic around puberty (similar to FA), but start btw age 418

Low plasma -tocopherol concentrations

Mutation in TTPA, the gene encoding the -tocopherol transfer protein

Ataxia with Vit. E Deficiency (AVED)

Presentation
Progressive ataxia Early loss of proprioception (especially distal joint position and vibration sense) Areflexia Dysdiadochokinesia Positive Romberg sign

Head titubation
Retinitis Pigmentosa Decreased visual acuity Positive Babinski sign

AVED
Treatment:
lifelong high-dose oral vitamin E supplementation If high-dose vitamin E treatment begins before, the onset of symptoms, symptoms never develop. If this treatment begins early in the progression of the disease, most symptoms are reversible. Without treatment: wheelchair bound btw ages of 11 to 15

Vitamin E deficiency

Hemolysis Neurological:

Early: hyporeflexia,impaired proprioception/vibration sense, distal muscle weakness, nyctalopia Later: truncal/limb ataxia, Neuro-opthalmologic (Limited upward gaze & dissociated nystagmus); areflexia, dysphagia/dysarthria

Vitamin B3 (Niacin)

Food sources: Meat, fish, poultry, enriched and whole grain breads, fortified cereals
Function: Assists in digestion and the conversion of food into energy; important in the production of cholesterol

RDA:

Men: 16 milligrams/day Women: 14 milligrams/day

Pregnant Women: 18 milligrams/day

Breastfeeding women: 17 milligrams/day

Vitamin B3 (Niacin)

Diet (corn)
Carcinoid syndrome

Anti-TB drugs: Isoniazid

Other drugs: Azathioprine, 6-MP, 5Fluorouracil, and Carbidopa Hartnup disease Chronic alcoholism

Pellagra (Vitamin B3)

Triad: Diarrhea, Dementia, Dermatitis GI -diarrhea(50%), N/V, poor appetite

Dermatological-hyperpigmented rash Neuropsychiatric symptoms: insomnia, anxiety, disorientation, delusions, dementia, encephalopathy, depression

Pellagra (Vitamin B3)

Treatment: 100mg Nicotinamide PO q6h

Preferred over niacin due to vasodilation(flushing)

Vitamin A

Food sources: Sweet potato with peel, carrots, spinach, fortified cereals, cod liver oil
RDA:

Men: 900 micrograms/day

Women: 700 micrograms/day

Vitamin A
Vision: integrity of eye & formation of rodopsin necessary for dark adaptation.
Regulation of gene expression: vital to cell differentiation & physiologic processes Immunity: important for activation of T lymphocyte, maturation of WBC & integrity of physiological barrier. Bone development

Vitamin A
Causes:

Deficiency due to diet rare in industrialized countries, common in Africa, S. America and Southeast Asia Fat malabsorption: CF, IBD, cholestatic liver disease eg. PBC, small bowel bypass surgery Urine overexcretion:tuberculosis, UTI, cancer, pneumonia and nephritis.

Vitamin A deficiency

Nyctalopia/complete blindness Xerophthalmia Keratomalacia Poor bone growth

Dermatological: hyperkeratosis, phrynoderma, destruction of hair follicles

Dry skin, dry hair

Poor bone growth

Impairment of humoral and cell-mediated immune system response via effect on T lymphocytes and phagocytes

Keratomalacia

Bitot spots